1. BACTERIAL STRUCTURE, PHYSIOLOGY, AND GENETICS
BACTERIAL CELL WALL: From the inside out.
• GRAM-POSITIVE:
o Plasma Membrane:
 Contains transport enzymes.
 In oxidative bacteria, contains proteins for oxidative
phosphorylation.
 Contains no sterols.
 Serves as the attachment site for segregation of DNA (cytokinesis).
o Peptidoglycan Cell Wall: MUREIN is the name of the cross-linked
substance making up the cell wall.
 STRUCTURE:
 Alternating chains of N-Acetyl-Glucosamine (NAG) and
N-Acetyl-Muramic Acid (NAM), connected together in
1,4-linkages.
 Each Muramic Acid has a tetrapeptide of alternating D
and L amino acids.
 Cross-links are made between adjacent chains, between the
third amino acid of one chain and the terminal D-Ala of
the other chain.
 TEICHOIC ACID is also contained within the Peptidoglycan
wall.
 STRUCTURE: Polymers of Ribitol Phosphate and
Glycerol Phosphate.
 Lipotechoic Acid is teichoic acid hooked to a glycolipid in
inner membrane.
 Teichoic Acids are major antigenic determinants of a cell's
specificity.
 PROTOPLAST forms when a bacterium is insensitive to lysis
from Lysozyme which normally lyses the bacterial cell wall.
 Forms when the cell is in a medium isotonic with its
interior.
 This is one form of environmentally-induced bacterial
resistance.
• GRAM-NEGATIVE
o Plasma Membrane
o PERIPLASMIC SPACE: That area between plasma membrane and
peptidoglycan sheath.
o Peptidoglycan Layer: Much thinner than the Gram-Positive
Peptidoglycan wall. It has been greatly reduced, with part of it
contributing to the periplasmic gel.
o LIPOPOLYSACCHARIDE (LPS) COAT: Outer covering of gram-
negatives.

2.  Endotoxin: LPS coat is the basis for gram-negative bacterial
endotoxin, which causes anaphylaxis.
 STRUCTURE:
 Lipid-A: Toxic component.
 Oligosaccharide Side Chain: Antigenic determinant
 BRAUN'S LIPOPROTEIN: Anchors the outer membrane
to the peptidoglycan layer. It actually connects to the third
amino acid in each peptidoglycan chain.
 BAYER'S JUNCTIONS: Zones of adhesion between the
outer and inner membrane.
o SPHEROPLASTS result in gram-negatives if you attempt to kill resistant
cells with lysozyme. Part of the periplasmic space remains intact.
• ACID-FAST BACTERIA: Mycobacteria. Share similar staining properties as
Gram-Positive.
o MYCOLIC ACID: They have an outer coat of waxy material made of
Mycolic Acid, which is extremely impermeable.
CELLULAR STRUCTURES:
• CAPSULE: Polysaccharide slime that can evade host defenses and adhere to
surfaces. They are virulence factors.
o Streptococcus Pneumonia
• FLAGELLA: Helical protein made of flagellin
o Types of Flagella:
 Monotrichous: Single flagellum.
 Lophotrichous: Two or several flagella oriented in a bipolar,
linear fashion.
 Peritrichous: Flagella oriented all about the cell.
o Basal Body: Intracellular structure that anchors the flagellum.
• PILI: Extensions of cytoplasmic membrane with little openings. Made of pilin.
o Common Pili
o SEX PILI: Special kind of pili.
• CYTOSOL:
o Ribosomes: 30S + 50S subunits = 70S ribosomes.
• SPORE: Produced by some Gram positive rods.
o It is produced in response to poor nutrition.
o It is made of a coat that is keratin-like and rich in Cys.
o Has special chemical called dipicolinic acid.
BACTERIAL GROWTH:
• TEMPERATURE
o PSYCHROPHILES: Grow best at cold temperature.
o MESOPHILES: Grow best at medium temperature. All pathogenic
bacteria are mesophiles.
o THERMOPHILES: Grow best at hot temperature.

3. BACTERIAL SECRETIONS:
• Extracellular Proteases are secreted to degrade host ECM, lipid, DNA, and
proteins.
• EXOTOXINS: Secreted substances that exhibit host toxicity.
o A-B TOXINS: Examples = Cholera Toxin, Diphtheria Toxin. Exotoxins
that ultimately act intracellularly.
 STRUCTURE: Two major subunits. The B portion binds to the
cell and the A portion is injected into cell to exhibit toxic effect.
 A = Activity Subunit.
 B = Binding Subunit.
 SIMPLE A-B TOXIN:
 Monocistronic (encoded by one gene)
 Two subunits are covalently connected by disulfide bond.
 COMPLEX A-B TOXIN: Multiple subunits of B and only one A
subunit.
 Polycistronic (encoded by multiple genes)
 Subunits also linked by disulfide bonds.
o MEMBRANE-DISRUPTING TOXINS: Pore-forming toxins.
 No enzymatic activity -- only ability to insert into cell membrane.
o SUPERANTIGENS: Toxins of superantigen class that indiscriminately
bind to MHC-II and TCR, and thus induce polyclonal activation of T-
Cells.
 Examples:
 Staph Enterotoxin
 Strep Exotoxin-A
 TSS Toxin
BACTERIAL CELL TRANSPORT:
• PASSIVE TRANSPORT
• ACTIVE TRANSPORT: Active means of transporting molecule (nutrients such
as lactose) into the bacterial cell.
o PROTON MOTIVE FORCE: Resistant to shock. Transport facilitated
by the electron transport chain.
 Protons are pumped out of the cytoplasmic membrane into
periplasmic space.
 Protons spontaneously migrate back in the membrane, with their
concentration gradients, through ATP-Synthase channels to
generate ATP.
o ATP-DEPENDENT TRANSPORT: Sensitive to shock. Direct
dependence on ATP for transport.
 Binding Protein is also required to get substance in the cell. This
protein is in the periplasmic space.
 Transporter Protein must also be present in inner cytoplasmic
membrane.

4. • GROUP TRANSLOCATION: Phosphorylate the sugar as it is brought into the
cell (glucose ------> glucose-1-phosphate), in order tto maintain concentration
gradient.
o Phosphotransferase (PTS) System is the name of the group-transport
system for glucose.
• IRON TRANSPORT: SIDEROPHORES, iron-sequestering proteins, are
secreted by bacterial cells.
o Siderophore bind the iron and then interact with receptors on bacterial
membrane, to bring in the iron.
o Siderophore-iron complex is endocytosed into cell.
o Iron is an essential mineral for all bacteria.
BACTERIAL METABOLISM:
• Embden-Meyerhof Glycolysis: Standard pyruvate-forming anaerobic glycolysis
o Streptococcus
• Mixed-Acid Fermentation: Form formic acid and acetic acid as byproducts.
o Escherichia Coli
o Enterobacteriaceae
• Butanediol Fermentation: Enterobacter
• Butyric Acid Fermentation: Clostridium
• Aerobes: Mycobacterium Tuberculosis
OXYGEN NUTRITION:
• FREE RADICAL OXYGEN:
o SUPEROXIDE DISMUTASE breaks down the Superoxide Anion, O2-2.
It is required for bacteria to survive in the presence of oxygen.
o CATALASE breaks down Hydrogen Peroxide, H2O2. It is not required,
but some bacteria possess it.
• OBLIGATE ANAEROBES: Bacteria that undergo anaerobic fermentation and
cannot survive in the presence of oxygen.
o They do not have Superoxide Dismutase, thus O2 is poisonous as it will
yield oxidative radicals that cannot be broken down.
• OBLIGATE AEROBES: Bacteria that undergo strictly oxidative respiration and
require oxygen for survival.
o They do have Superoxide Dismutase and thus can survive in O2
• FACULTATIVE ANAEROBES: Bacteria that can undergo fermentation in the
absence of O2, or respiration in its presence.
o They do have Superoxide Dismutase and thus can survive in O2.
• AEROTOLERANT ANAEROBES: Bacteria that never undergo oxidative
respiration but can nonetheless tolerate the presence of oxygen.
o They do have Superoxide Dismutase.
o Streptococcus Pneumonia is an aerotolerant bacterium that has superoxide
dismutase but not catalase.

5. • MICROAEROPHILIC: They are facultative anaerobes, but they prefer low O2-
concentration conditions.
PEPTIDOGLYCAN SYNTHESIS: Occurs in three compartments of the cell.
• CYTOSOL: UDP-aided N-Acetyl-Muramic Acid is synthesized with a
pentapeptide chain hanging off it.
o The final product will have only a tetrapeptide. The extra residue is an
additional terminal D-Alanine.
• CELL MEMBRANE: NAM-Pentapeptide Precursor is attached to Bactoprenol
receptor in the plasma membrane.
o Inside the cell membrane, N-Acetyl-Glucosamine is added to the NAM-
Pentapeptide precursor.
• PERIPLASMIC SPACE (or OUTSIDE MEMBRANE): The NAM-NAG
Disaccharide is attached to the growing glycan chain.
o TRANSPEPTIDASE forms cross-links between the new subunit and the
existing chain.
 The terminal (fifth) D-Alanine is released as an energy-transducer
in order to fuel the transpeptidation reaction.
o PENICILLIN-BINDING PROTEINS (PBP's): Several proteins in the
periplasmic space, that are required to aid in the cross linking reactions.
CELL-SURVIVAL MECHANISMS:
• SOS-SYSTEM is invoked in response to damage done to DNA (see DNA repair
below)
• HEAT-SHOCK proteins are up-regulated in response to heat. Most of the
proteins are protein-chaperones that aid in folding proteins. They are needed in
higher concentration in presence of heat which threatens denaturation of proteins.
• SPORULATION: Formation involves a cascade of sigma-subunits (similar to
phosphorylation cascade), culminating in gene-regulation that cause spore-
formation.
CHEMOTAXIS: A series of "biased random walks" that results in directed movement.
• Flagellar Movement
o RUN: Counterclockwise rotation of flagella, which produces forward
motion.
o TUMBLE: Clockwise rotation of flagella, which causes bacteria to stay in
place.
• REGULATION: Bacteria goes toward attractant by balancing the relative
amounts of tumbles -vs- runs. E. Coli example:
o When concentration of attractant goes up, tumbles are suppressed and runs
take over.
o When concentration of attractant subsides, the tumbles take over.

6. o METHYL-ACCEPTING CHEMOTAXIS PROTEIN (MCP): It is
activated (autophosphorylation) when an attractant molecule binds to a
membrane receptor.
o TUMBLE-RESPONSE REGULATOR PROTEIN (CheY): At end of
signal cascade, it binds to a flagellar motor protein and causes the
productive (counterclockwise) motion of flagella.
 When attractant molecules disengage the receptor, the MCP re-
methylates, the CheY lets go, and the default tumble resumes.
o ACCOMMODATION: Spontaneous methylation of the MCP leads to
deactivation of the MCP.
 Accommodation resets the cell's sensitivity to the attractants, such
that a higher level is required for continued activation.
o MOLECULAR MEMORY: The overall basis for chemotaxis. The cell
senses its level of activation, and can only continue to be activated if it is
in a region of increased level of attractants, compared to where it was a
short time ago.
PHYSICAL BACTERICIDAL AGENTS:
• HEAT: Wet heat is more effective than dry heat.
• RADIATION: UV-Light
• FILTRATION
ANTIBIOTIC DRUGS
• beta-LACTAMS: They irreversibly inhibits Penicillin-Binding Proteins in the
bacterial periplasmic cell, thereby inhibiting peptidoglycan transpeptidation. All
are primarily bactericidal.
o PENICILLINS: beta-Lactam.
 HYPERSENSITIVITY is possible.
 PENICILLIN-G: Natural Penicillin, active against gram-positives
 TARGET: Streptococcus Pneumonia, Syphilis.
 RESISTANCE is due to beta-Lactamase, which cuts the
beta-Lactam ring.
 Staph Aureus produces an inducible protein called
Penicillinase and is thus resistant to Penicillin.
 METHICILLIN, OXACILLIN: Penicillinase-Resistant, Narrow-
spectrum Penicillins.
 TARGET: Staph Aureus is thus susceptible to these.
 AMPICILLIN: Broader-Spectrum Penicillin. It is broader-
spectrum because it can traverse the outer membrane of some
gram-negatives.
 TARGET: Used against gram-negatives.
 Not effective against Pseudomonas
 PIPERACILLIN: Extended-spectrum Penicillin

7.  TARGET: Pseudomonas and other gram-negatives, but not
gram-positives.
o CEPHALOSPORINS: Another class of beta-Lactams.
 HYPERSENSITIVITY is possible.
 FIRST-GENERATION: Targeted penicillin-resistant Gram-
Positive cocci and some gram-negative bacilli.
 SECOND-GENERATION: Has an extended spectrum to include
more gram-negatives.
 It is resistant to some plasmid-encoded beta-lactamases,
extending its spectrum.
 THIRD-GENERATION: Is even-broader spectrum and is most
effective against gram-negatives.
 TARGETS: E. COLI and other culprits of UTI's.
o CARBEPENAMS: beta-Lactam drug with different synthetic structure
than Penicillin (containing Sulfur).
 IMIPENEM is the only Carbapenem available in US.
o MONOBACTAMS: beta-Lactam drug
 AZTREONAM is the only one used in the US.
 TARGET: Aerobic gram negatives. Not good for gram-
positives.
o beta-LACTAMASE INHIBITORS: Drugs that can sometimes be given
with beta-Lactams to aid in fighting resistant strains.
 CLAVULANIC ACID: beta-Lactam analog that binds
irreversibly to beta-Lactamase inhibitors.
 SULBACTAM: Another irreversible-binding beta-Lactam analog.
 These drugs should not be combined with Penicillinase-Resistant
Penicillin (i.e. Methicillin)
• VANCOMYCIN: Non-beta-Lactam inhibitor of Peptidoglycan assembly.
o TARGET: Multi-resistant gram-positives.
o SIDE-EFFECTS: CNS Toxicity. It is only used when necessary.
o RESISTANCE is due to modification of target site.
• POLYMYXINS: They inhibit cell membrane function. Simple peptides with a
cationic detergent effect.
o ONLY TOPICAL USE: They interact with host cell membranes and thus
are not used systemically.
• TRANSLATION INHIBITORS: 30S RIBOSOMAL SUBUNIT
o AMINOGLYCOSIDES:
 SIDE-EFFECTS: They all exhibit ototoxicity and renal toxicity
 STREPTOMYCIN:
 TARGET: Must work against Aerobes -- drug is
transported into bacterium via oxidative phosphorylation in
membrane.
 It is not effective against any intracellular pathogens
because it can't get into Eukaryotic cells -- no
Rickettsiae or Chlamydiae.
 GENTAMICIN

8. o TETRACYCLINE: Inhibits 30S Ribosome, but binds to a different site.
Bacteriostatic.
 TARGET: Broad Spectrum. Active against Rickettsiae and
Chlamydiae.
 Affects normal gut flora.
 Don't give with milk: It chelates calcium.
 RESISTANCE has developed, especially due to overprescription.
• TRANSLATION INHIBITORS: 50S RIBOSOMAL SUBUNIT.
o CHLORAMPHENICOL: Inhibits Peptidyl Transferase in 50S subunit.
 SIDE-EFFECT: Some toxicity.
 TARGET: Broad-spectrum antibiotic.
 Diffuses across blood-brain barrier, therefore useful for
Meningitis.
 RESISTANCE: Due to a plasma-encoded Acetyltransferase that
acetylates and inactivates the drug.
o ERYTHROMYCIN: Binds to the same site as Chloramphenicol.
 TARGET: Broad-spectrum. Has both bacteriostatic and
bacteriocidal activity.
 RESISTANCE: Methylation of the ribosomes, causing the target-
site to be blocked.
• QUINOLONES: They inhibit DNA replication. Specifically they target DNA
Gyrase, which forms or removes supercoils during replication (like a helicase).
o NALIDIXIC ACID:
 TARGET = Urinary tract infection because it gets into urine well.
o FLUOROQUINOLONE: Good body distribution and popular drug.
 TARGET = Anaerobics.
 RESISTANCE due to alteration of the DNA Gyrase target enzyme.
• RIFAMYCIN: Inhibits transcription by binding to RNA-Polymerase.
o TARGET = Aerobic bacteria, Mycobacterium Tuberculosis.
• METABOLIC INHIBITORS: Inhibits steps in Folate Synthesis, a precursor
required for bacterial growth, which bacteria normally make themselves.
o SULFONAMIDE: Structural analogue of PABA.
 MECH: It inhibits Dihydropteroate Synthetase, preventing
formation of Dihydrofolic Acid.
 TARGETS: UTI's caused by E. COLI.
 RESISTANCE: Plasma-encoded, it modifies the target enzyme,
reducing its affinity for the drug.
 Resistance can also occur by reduced permeability of the
bacterium.
o TRIMETHOPRIM: Structural analogue of Dihydrofolate.
 MECH: It inhibits Dihydrofolate Reductase, preventing
formation of Tetrahydrofolic Acid.
 RESISTANCE is by same mechanism as above.
o Sulfonamide and Trimethoprim together have a synergistic effect.
DNA REPLICATION and TRANSCRIPTION: Bidirectional and Semiconservative.

9. • DNA Polymerase III: The most important bacterial polymerase enzyme.
o DNA Poly I and II are used in repair.
• SIGMA FACTOR: A protein that is required for the RNA Polymerase to
recognize the promoter site and effect transcription.
o Once transcription begins, the sigma factor falls off.
• TRANSCRIPTION:
o Polycistronic: Multiple genes encoded in one transcript.
o Coupled Transcription/Translation: Ribosomal translation begins
before transcription is even complete, and there is no post-transcriptional
modifications (i.e. splicing).
GENETIC MUTATIONS and REPAIR:
• Types of Mutations:
o TRANSITION: A mutation exchange of purine for purine or pyrimidine
for pyrimidine.
 CAUSES:
 UV-Radiation
 Deaminating and alkylating agents
 base analogs.
 Spontaneous
o TRANSVERSION: A mutation exchange of purine for pyrimidine, or
pyrimidine for purine.
 CAUSES: Strictly spontaneous; no causative agents.
o MICRO INSERTIONS / MICRO DELETIONS: They can be frameshift
mutations, and they can be offset by a corresponding mutation
downstream from the original, to restore the reading frame.
o Missense: Change of coded amino acid from one residue to a different
residue.
o Nonsense: Change of coded amino acid to a stop codon, truncating the
protein and rendering it dysfunctional.
o CONDITIONAL LETHAL MUTATION: A mutation that is lethal
under one condition (usually temperature) but not another. This is most
frequent with Temperature-Sensitive Mutants.
 Permissive Condition: The condition under which the bacterium
survives. (Low temperature)
 Non-Permissive Condition: The condition under which the
bacterium perishes. (High temperature).
• MUTAGENS:
o CHEMICAL MUTAGENS
 Base Analogs: Compounds that resemble a nucleotide base and
cause mispairing when inserted.
 5-Bromouracil resembles Thymine and gets in the place of
Thymine in a chain, which ultimately can lead to an A--T
to G--C transition.
 Chemical Compounds

10.  Intercalating Agents
o PHYSICAL MUTAGENS
 Heat: Causes depurination, removes purine from DNA backbone,
potentially resulting in deletion.
 UV-Light: Causes formation of Thymine dimers
 X-Ray Radiation: Cause double-stranded breaks in DNA that lead
to deletions.
 Can also cause radical formation.
• ERROR CORRECTION: Briefly, normal correction mechanisms.
o EDITING: Transiently incorporated bases are examined to make sure
they are paired correctly. If they aren't then they don't stick in the first
place.
o PROOFREADING: 3' ------> 5' exonuclease activity of DNA
polymerase, to make sure all bases are paired correctly. A mispair will
undergo excision repair by the DNA polymerase.
o Post-Replicative Correction
o SOS REPAIR SYSTEM: The SOS Repair system is invoked when
Thymine dimers are formed from UV damage. It is a "last-resort" repair
system, and is error-prone.
 Normally, excision-repair occurs which is much more accurate.
 Lex-A gene is the gene that expresses a repressor proteins which
normally suppresses SOS activity. When LexA is turned off, the
SOS system is induced..
 REPAIR PROCESS:
 Rec A gene is activated by the presence of single-stranded
DNA which is indicative of DNA damage.
 RecA then interacts with LexA, causing it to autocleave
and turning it off ------> SOS System activates.
 umuC and umuD are SOS repair proteins, normally suppressed by
the Lex-A gene. These proteins make DNA polymerase less base-
specific (more error-prone).
DIRECTED -VS- UNDIRECTED MUTAGENESIS: Mutation occurs in an undirected,
random fashion.
• An antibiotic resistance mutation does not occur as the result of introduction of
antibiotic. It can occur at any time.
• FLUCTUATION TEST: Take two strains, grow them up, introduce
Streptomycin into each of them at the same time, and later count how many
colonies you have.
o RESULT: You will have different numbers of colonies in each strain,
because Strep-R mutations occurred at different times in each strain.
o CONC: Strep-R mutations occur independently of the introduction of
Streptomycin.

11. • Mutation Frequency: The number of mutants per total viable population. This
quantity is not a good measure of mutation, because there's no baseline population
to compare to.
• Mutation Rate: The probability of a mutation per cell per generation. A much
better measure of mutation.
AMES TEST: Test for mutagenesis, by measuring the number of backward (reversion)
mutations in His- Salmonella cells grown without Histidine.
• Introduce Rat-Liver Microsomal Oxidases into the bacterial culture. These
enzymes are added in order to metabolize the potential carcinogens (mutagens), as
most require metabolic activation before becoming mutagenic.
• RESULTS: The more bacterial colonies you get, (bacteria living on the His- bare
medium), the greater the mutagenicity of the compound being tested.
REVERSIONS: Reversal of a mutation to restore the wild-type.
• True Reversion: True backward mutation. Changing the original mutation back
to the same way it was. The original mutation is replaced.
• SUPPRESSION: A second mutation which in some way restores or partially
restores the function of the original mutated protein. The original mutation
remains in place.
o INTRAGENIC SUPPRESSION: Second mutation within the same gene.
 Restore Reading Frame: A micro deletion to suppress a micro
insertion, or vice-versa. This often will restore a truncated
(nonsense) protein.
 Restore Tertiary Structure: Suppression of a point mutation that
replaces another residue somewhere else in the protein, which in
some way makes the protein once again fold correctly in its tertiary
conformation.
o INTERGENIC SUPPRESSION: Suppressor mutation alters a tRNA
Anticodon so that it recognizes what would otherwise be a stop codon
(UAG).
 One base-pair of the anti-codon mutates such that the tRNA then
codes an amino acid for the stop codon. Depending on the
mutation, three surrogate amino acids are possible: Tyr, Ser, Gln.
 This might supress the original mutation by eliminating the stop
codon and allowing the protein to read past a nonsense mutation.
o This process is also called Codon Specific Translational Suppression.
TRANSFORMATION: Uptake of naked DNA
• ARTIFICIAL TRANSFORMATION: Occurs in labs, to make DNA probes.
o Electric Voltage
o CaCl2

12. • PHYSIOLOGICAL TRANSFORMATION: Natural uptake of naked DNA,
usually derived from dead bacterial cells in the environment.
o GRAM-POSITIVES: The cells must be competent in order to undergo
transformation and take up naked DNA.
 COMPETENCE: The ability for gram-positives to take up naked
DNA.
 COMPETENCE-FACTOR: Protein secreted by competent cells,
that has autolysin activity (to permeate the membrane), and digests
exogenous DNA into absorbable fragments.
 Double-stranded DNA is denatured to single-stranded and
then taken into the cell indiscriminately.
 If it shares homology with any of the host DNA (genome or
plasmid), it can be incorporated into genome via
generalized recombination.
 Any foreign DNA that has no homology will be degraded.
o GRAM-NEGATIVES: There is no competence-factor per se.
 Only homologous DNA is taken into the cell, and it is taken in as
double-stranded.
 Transformosomes: Extrusions of outer membrane formed in order
to facilitate DNA uptake.
TRANSDUCTION: Transfer of host genomic DNA via a bacteriophage virus.
• GENERALIZED TRANSDUCTION: Non-specific transfer in which any piece
of DNA may be transferred to any cell.
o PROCESS: Bacteriophage incorporates a random piece of host-DNA
during packaging. This is an error in viral packaging during the lytic cycle,
which occurs infrequently.
o It occurs in Gram-Positives -- Staph and Strep.
o MAPPING: If a single virion incorporates two genes from the host, then
you know that those two genes are in close proximity to each other.
• SPECIALIZED TRANSDUCTION: Transfer of genes flanking a specific Att
attachment region on the host-genome.
o Viral genome picks up a couple of genes flanking its attachment site when
it excises from the host genome. This is an error in viral replication which
occurs infrequently.
o Site-Specific Recombination: When phage gets into recipient, it
recombines with it replicatively in a site-specific fashion, creating a
diploid of whatever genes it contained.
o lambda-Phage: It can undergo specialized transduction, creating a
DIPLOID cell in the recipient.
 It inserts next to the Gal marker in host genome, where it resides as
a prophage until it is induced to undergo lytic cycle.
 Once in a million times by accident, lambda-phage takes a piece of
the host genome with it, forming lambda-D-Gal Phage (D =
defective).

13.  When this phage infects another cell, it makes the other cell
diploid for the piece of replicated DNA -- the Gal gene.
 The recipient may now have a Gal- and Gal+ copy of the
gene.
o PHAGE CONVERSION: Imparting genes onto a recipient that were
inherently part of the phage genome to start with -- not part of the host
genome.
 In this case, transduction is not the consequence of a random error.
Rather, every infected cell becomes transduced with the gene.
Types of Recombination:
• SITE-SPECIFIC RECOMBINATION: Replicative recombination in which
only a small degree of homology is required, but which occurs at a very specific
site.
o Recombination is replicative and results in a partially diploid product.
• GENERALIZED RECOMBINATION: Non-replicative recombination that
requires presence of the Recombinase (Rec) Gene to effect recombination.
o A high degree of homology is required.
• ILLEGITIMATE RECOMBINATION: Replicative recombination in which no
homology is required, such as with R-Plasmids.
o Transposable Elements undergo illegitimate recombination.
CONJUGATION: Classical conjugation of the F-Plasmid.
• EPISOME: A series of genes that can exist as a plasmid or can incorporate
themselves into the genome. F-Factor is a plasmid.
• F-FACTOR: Plasmid encoding for Pili which allows for sexual conjugation
(transfer) of genetic material.
o A bacterium that possesses the F-factor is F+ (male).
o A bacterium that lacks the F-Factor is F- (female).
o STRUCTURE:
 Contains a sex pilus gene
 Contains an Ori of replication.
• Classical Conjugation: Replicative transfer of the F-Factor from F+ cell to F-
cell. This induces the F- cell to become F+.
• High Frequency Recombination (HFR): When the F-Factor is incorporated into
the host genome, the cell becomes known as an HFR Cell. HFR-Cells are F+ but
cannot transfer their F-Factor to recipients.
o CONJUGATION in this case does not result in converting a cell to F+,
because incomplete transfer of the genome occurs, and some of the F-
Factor genes are not replicated.
o The Ori site of the F-Factor is the origin of replication for the entire
genome in this case. Because the genome is too long to be transferred in
its entirety, some portion of the F-Factor almost always is not transcribed.

14. o F' CELL is formed when the F-Factor excises back out of the main
chromosome, and takes a few chromosomal genes with it. (Imperfect
excision).
 SEXDUCTION: Transfer of F factor to an F- recipient, making it
F+.
 The recipient cell is then known as Secondary F' Cell because it is
diploid for the transferred chromosomal genes.
TRANSPOSABLE ELEMENTS: Genes that can transfer themselves from one location to
another by some mechanism.
• INSERTION SEQUENCES (IS-ELEMENTS): Basically, just one gene,
flanked by inverted repeats on either side.
o The single gene on the inside codes for Transposase, the protein that
allows the gene to jump around.
• TRANSPOSONS: Insertion-sequences that contain more genes on the inside, and
are bounded flanked by IS-elements on either side.
o TnA-TYPE TRANSPOSONS: They contain genes that code for
transposases, which allow for movement. Thus they can move be
illegitimate, replicative recombination.
 Genetic Contents: May contain various resistance genes.
 tnpA: Transposase gene. Required for transposition.
 tnpR: Transposon resolvase gene. Required for
transposition.
 bla: beta-Lactamase (resistance) gene.
o COMPOSITE TRANSPOSONS: They do not contain the tnpA and tnpR
genes -- only the IS-elements plus any genes that code for resistance.
 Recombination with composite transposons requires the Rec-A
gene, occurs by generalized recombination, and is non-replicative.
 They are still flanked by inverted repeats.
• TRANSPOSITION: Process = Donor plasmid recombines with recipient
plasmid in a process of illegitimate, replicative recombination.
o They form a large composite transposon known as a Cointegrate.
o Resolvase then resolves the Cointegrate into two plasmids, both of which
contain the transposon and internal (resistance) genes.
• MUTATION: Transposons can cause mutation in the genes they donate to.
o They can be spliced into the middle of the gene, turning the gene off.
o They can take large pieces of DNA with them when they transpose.
o They can change regulation of a gene, by moving a gene close to a new
promoter.
PLASMIDS: Covalently Closed circular DNA, existing independent of the host genome.
• SIZE: 1.7kb - 700kb
• SELF-REPLICATION: Plasmids can replicate independently, but they depend on
host polymerase replication machinery.

15. o OriV: Origination of Vegetative Replication. All Plasmids have an origin
of replication.
o Because of self-replication, plasmids can be transferred between
phylogenetically unrelated species.
• PLASMID SURVIVAL: Plasmids have a set number of copies per cell. Cell can
withstand only a certain number of plasmids. This is a mode of selection against
plasmids, and, all other things held constant, plasmids are selected against.
• CONJUGATIVE PLASMID: A plasmid containing genes for making Pili. This
is not an F-Factor, but a different "non-classical" form of conjugation.
o GENETIC CONTENTS:
 OriV: Origin of replication.
 OriT: Origin of Transfer
 tra: Transfer Genes that code for Pili.
 Resistant-determining gene.
o TRANSFER:
 Conjugative plasmids can direct the transfer of non-conjugative
plasmids. All a host-cell needs to transfer all of its plasmids is a
single conjugative cell that can build the pili.
 There is no transfer of genomic DNA (as in F-Factor and HRF) --
only transfer of the plasmid itself.
• NON-CONJUGATIVE PLASMID: Can only be transferred in the presence of a
conjugative plasmid.
o GENETIC CONTENTS
 OriV: Origin of replication.
 nic: A "pre-OriT" site, or nicking site, that becomes OriT once
cleaved.
 mob: It codes for an endonuclease that cleaves the nic site ------>
OriT, enabling the non-conjugative plasmid to transfer to a new
cell in the presence of Pili.
 Resistance-determining gene.
• R-PLASMIDS: Also known as Multi-Resistant Transfer Plasmids (MTRP). Can
be either Conjugative or Non-Conjugative.
o GENETIC CONTENTS:
 r-Region: Contains one or multiple resistance genes.
 The resistance region is usually flanked by IS-elements and
contained on transposons.
 RT Region: Contains gene for transfer.
o TRANSFER: The r-Region is usually contained on transposons. Transfer
primarily occurs by conjugation and illegitimate recombination.
 Conjugation allows transfer of resistance between bacterial
species.
 Generalized Transduction can also occur within the same species
-- for Gram-positives Strep and Staph.

16. Return to top
MYCOLOGY
BASIC FUNGAL STRUCTURES:
• STEROLS:
o ERGOSTEROL, rather than Cholesterol, dominates cytoplasmic
membrane. It is a frequent target for anti-fungal drugs.
o ZYGOSTEROL, precursor to Ergosterol, is also found in cell wall.
• CELL WALL:
o It is made of three polysaccharides unique to fungi.
 CHITIN: Long unbranched chains of N-Acetylglucosamine
 MANNAN
 GLUCAN
o CHITIN SYNTHASE: The cell wall is located outside of the cell
membrane, and there is a periplasmic space in between the wall and cell
membrane. Chitin Synthase is located in this space and is thus a potential
target for antifungal drugs (but none are developed yet).
• Reproductive Structures:
o MOLDS:
 CONIDIA: Asexual reproductive elements.
 The TIPS of the conidia are crucial for growth. They spray
digestive enzymes which allow to penetrate through soil as
they grow.
 GERMINATION: Formation of many hyphae and then a
mycelium. The mold is most susceptible to phagocytic
attack during the germination stage.
 MYCELIUM: Intertwined mass of budding HYPHAE. Because it
is too big, mycelia are not easily digested by phagocytes.
 SEPTATE: Septate fungi form cell walls, or septa, as they
grow up along each hyphae.
 NON-SEPTATE: Non-septate fungi form each hyphae as
one continuous cell.
 FRUITING BODIES are formed off of the mycelium, whenever
nutrients become scarce. Those fruiting bodies can leave to form
new conidia.
 SPORES: Sexual reproductive elements.
 ASCOSPORE: Most common spore form, four or eight
asci in each spore.
o YEAST: Reproduce strictly by budding, where each daughter cell juts out
from its parent. Size of 2-60 micron.

17.  BUDDING SCAR: Yeast divide by budding, forming septa, and
then finally separating from one another. A characteristic scar is
left on the cell after its daughter cell has separated from it.
 PSEUDO HYPHAE are formed when the yeast don't actually
separate.
 POLARITY: Yeast budding can be BIPOLAR or
MULTIPOLAR. Multipolar yeast have budding scars all over it.
• DIGESTIVE VACUOLES: Degradative role. These are equivalent to (but not
the same as) lysosomes.
INFECTION:
• Abrasion
• Maceration: Skin lacerated and wet.
• Burns
IMMUNITY: Immunity against fungal infections is cell-mediated -- not humoral.
• We have natural antibodies to fungal galactomannans, except these only are
expressed in the mold form.
• HYPHAE and YEAST CELLS: Neutrophils are the primary defense.
• DIMORPHICS: They are slowed, but not killed, by Activated Macrophages
(IL2, IFN-gamma).
MYCOTOXINS: Fungal toxins, produced in the environment, but not in-vivo, once the
fungus has already infected. No known fungal toxins are produced in-vivo. All chemical
tissue damage is the consequence of host-defenses.
FUNGAL CLASSIFICATION:
• ZYGOMYCETES: Forming Zygospores, phylogenetically simple and similar to
Euglena.
• ASCOMYCETES: They create eight ascospores inside each ascus, or sexual
reproductive structure.
o Many of the fungi previously classified as Fungi Imperfecti may actually
fall into this category. It depends on whether or not the have sexual
structures, and whether those structures have been discovered.
o Thus you could say that most pathogens fall into this class.
• BASIDIOMYCETES: No medically important fungi are in this class. They are
the most structurally complex.
• FUNGI IMPERFECTI: Fungi, mostly Dimorphics, that do not have a sexual
stage of reproduction.
o There are no sexual spores, and fungi reproduce only by forming conidia.
ANTI-FUNGAL DRUGS:

18. • POLYENES:
o AMPHOTERICIN-B: Attacks ergosterol in the fungal cell wall, causing
cell lysis.
 IV-ADMINISTRATION: Amphotericin-B is not absorbed in the
GI-Tract and must be administered IV.
 TOXICITY: It is highly toxic because ergosterol is very similar to
cholesterol, thus Amphotericin also has cross-reactivity to
cholesterol in human cell membranes.
 FUNGICIDAL: They cause fungal cell lysis.
 SIDE-EFFECTS: Chills, fever, dyspnea can be seen.
 RENAL DYSFUNCTION is the most common, virtually
inevitable complication.
o NYSTATIN: Alternative polyene similar to Amph-B.
• AZOLS: They all work by blocking the CYTOCHROME-P450 Synthesis of
Ergosterol, thus inhibiting fungal growth. Specifically it interferes with
conversion of lanosterol to ergosterol.
o FUNGISTATIC: Action is fungistatic.
o FLUCONAZOLE: Most popular azol, used for disseminated dimorphic
infections.
 Fluconazole is often used prophylactically in AIDS patients
(indefinite treatment is required after exposure to a systemic
pathogen).
 Fluconazole is the single best treatment for Cryptococcal
Meningitis.
 CANDIDIASIS RESISTANCE: It will kill Candida Albicans, but
other species of Candida are resistant. Thus treatment with
Fluconazole can result in a Candida non Albicans disseminated
infection.
o ITRACONAZOLE: Also used for systemic infections.
• GRISEOFULVIN: Acts on microtubules within fungal cells, inhibiting growth.
o Only works on superficial fungi.
o It is very slow acting and thus has limited utility.
• POTASSIUM IODIDE: Singularly useful against Sporothrix Schenckii. It is
only to toxic to the yeast form -- not the mold form.
• FLUCYTOSINE: Active against yeasts -- Cryptococcus Neoformans and
Candida Albicans. It is an analog of cytosine which can block DNA synthesis or
transcription.
o RESISTANCE can occur, making the drug impermeable to fungal cells.
o SYNERGY: It is most often used in conjunction with Amphotericin-B,
where it has synergistic effects.
• UK-109,496: Experimental triazole drug with broad spectrum anti-fungal
properties.
o It fungicidal for Aspergillus
o It is the strongest binder to Cytochrome-P450. It binds so strongly that it is
classified as Fungicidal.

19. • MINIMUM INHIBITORY CONCENTRATION (MIC): The minimum
amount of drug necessary to effect stasis or lysis of pathogenic cells.
LAB DETECTION OF FUNGI:
• SABOURAUD'S AGAR: The most commonly used agar for culturing fungi for
identification.
• MORPHOLOGY: Molds are usually identified by the morphology of their
conidia.
o This process is slow because conidium production may not occur for
weeks, similar to waiting for a flower to bloom.
• EXOANTIGEN TEST: Most of the dimorphic fungi are identified by an
immunodiffusion assay utilizing distinct antigens on their cells.
CUTANEOUS FUNGI: DERMATOPHYTES are the names of the fungi that cause
superficial infection.
SYSTEMIC FUNGI: Most systemic fungi are thermally dimorphic.
• THERMAL DIMORPHISM: Fungi exist as mold at ambient temperature, but
convert to Yeast form at body temperature.
o CONVERSION:
 Converting from mold to yeast form puts new adhesins on their
cell membranes, which allows them to invade and makes them
pathological.
 Cell wall loses disulfide bonds during conversion.
o GALACTOMANNANS: Antigenic cell wall component. We have
antibodies to these, but they are usually only present in the mold stage.
They disappear in the yeast stage, thus the yeast stage is more virulent.
• HISTOPLASMA CAPSULATUM: Thermally Dimorphic
o STRUCTURE: Shares the same sexual precursor with Blasto: Ajellomyces
o INFECTION: Histoplasma conidia range in size, from Macroconidia to
Microconidia.
 TUBERCULATED MACROCONIDIA are found in mold form
and inhaled.
 MICROCONIDIA can also be inhaled and reach the lungs.
 After conversion, budding yeast are small enough (5micron) that
they can get clear down to the alveoli when inhaled. Histoplasma
is found in CHICKEN SHIT.
o DIAGNOSIS:
 Look for H-Antigen on immunodiffusion assay of the URINE.
The body concentrates the antigen in the urine, making it the
fastest, easiest test (although it's expensive).
 DNA-Probe for 16s RNA
 Demonstrate thermal conversion in culture. Conversion will yield
small, single-budding yeast.

20.  Demonstrate intracellular parasites inside macrophages in patient's
bone marrow.
o PATHOPHYSIOLOGY: Acute Histoplasmosis is most similar to
tuberculosis in its histology and pathophysiology.
 Pulmonary Infection will leave little calcified granulomas that can
be silent in immunocompetent patients.
 Histoplasma live intracellular, inside alveolar macrophages. This
is their route of dissemination, hence primary sites of
dissemination are reticuloendothelial.
o DISSEMINATION: Histoplasmosis disseminates primarily to
Reticuloendothelial System (liver and spleen).
o AIDS: It is common in AIDS, suggesting that CD4+ is essential to host
defense.
• BLASTOMYCES DERMATITIDES: Thermally Dimorphic
o STRUCTURE: Shares the same sexual precursor with Histo: Ajellomyces.
Blastomycoses exhibit broad-based budding.
o PATHOPHYSIOLOGY: Blasto also has huge conidia, but in yeast form it
is primarily extracellular rather than intracellular.
 It forms uncalcified granulomas in the lungs in
immunocompetent people. These granulomas are similar to the
cutaneous ones formed by Sporothrix.
o DIAGNOSIS:
 Skin lesions will be present, whereas in Histoplasmosis skin
lesions are usually absent.
 Still must demonstrate conversion in culture.
 Enzyme Immunoassay assay for Exo-Antigen-A, which will be
found in blood, CSF, or lymph fluid. This is the most sensitive test
for Blastomycosis.
o DISSEMINATION: It often disseminates to skin, bone.
o AIDS: It is NOT seen in AIDS, suggesting that CD4+ is not essential to
host defense. They don't know what is, though.
• COCCIDIOMYCES IMMITIS: Thermally Dimorphic. It is most similar to
Histoplasma in its presentation and involvement with AIDS.
o INFECTION: Initial infection is also pulmonary, and calcified granulomas
are formed.
o MORPHOLOGY: Arthroconidia initially infect.
o VALLEY FEVER: It forms valley fever and is found in the desert
southwest.
o DISSEMINATION: Relatively common. Can be found in skin, bone,
meninges, and later, mucocutaneous.
o DIAGNOSIS: Immunodiffusion assay for Antigen-C
• PARACOCCIDIOMYCES BRASILIENSIS: Thermally Dimorphic. It is most
similar to Blastomyces in its presentation and lack of involvement in AIDS.
o INFECTION: Initial infection is also pulmonary, and uncalcified
granulomas are formed.

21. o LOCATION: Central / South America. Similar distribution as
Coccidiomyces.
o DIAGNOSIS: Immunodiffusion assay for Antigen-P.
• CRYPTOCOCCUS NEOFORMANS: Dimorphic, but not thermally dimorphic.
o MORPHOLOGY: In tissue, it is a yeast with an enormous polysaccharide
capsule.
 The Capsule is susceptible to attack only by activated
macrophages, hence AIDS renders us helpless.
 The capsule also inhibits phagolysosome formation -- inhibits
phagocytosis.
 Size once desiccated is around 5micron, thus it gets into alveoli.
 SEXUAL FORM: In its sexual form it is a Basidiomyce.
o INFECTION: PIGEON POOP -- Desiccated cryptococcal yeast are found
in pigeon poop. Initially it is inhaled.
o CRYPTOCOCCAL MENINGITIS is the most common disseminated
form of the disease. Very common in AIDS.
 Phenol Oxidase: The fungi have this enzyme, which may explain
its affinity for the CNS.
 CNS needs epinephrine for their immunity, and this
enzyme may in someway block this pathway, making the
CNS susceptible.
 Alternatively, the fungi may be able to subsist on
Catecholamines since they can use it for nutrient.
o FOUR SEROTYPES: Four different antigen structures found on the
capsule.
 TYPE A: Found in USA, in AIDS
 TYPE B: Found in Australia (Eucalyptus trees), and not found in
AIDS strangely.
 TYPE C: Found in Australia (Eucalyptus trees), and not found in
AIDS strangely.
 TYPE D: Found in Europe, in AIDS.
SUBCUTANEOUS FUNGI: Infection occurs by a puncturing wound subcutaneously.
• SPOROTHRIX SCHENCKII:
o MORPHOLOGY: It has a mother-yeast cell once it converts, which gives
rise to cigar-shaped yeast daughter cells of about 10micron each.
o INFECTION: Get pricked with a rose-form. The mold-form is introduced
with infection, and it quickly converts to yeast form.
o SYMPTOMS: In immunocompetent people, just ulcerating skin papules
and lesions at site of infection, with no systemic symptoms if treated.
o DIAGNOSIS:
 Must demonstrate thermal conversion.
 Identify typical conidia: cigar-shaped yeast daughter cells with
mother yeast-cell.

22.  CONVERSION: Unlike the other dimorphics which convert at
37C, Sporothrix converts at 35C which is why it is a subcutaneous
yeast.
 Dermatophytes, which are strictly cutaneous molds, exhibit
the same behavior -- they are inhibited at 37C.
o DISSEMINATION:
 In immunocompromised, it can disseminate to skin, eyes, joints,
conjunctivae. Chronic arthritis is probably most prevalent
disseminated symptom.
 Sporothrix disseminates through Lymphatics.
o TREATMENT:
 Cutaneous Sporotrichosis is treated with oral KI.
 Systemic Sporotrichosis must be treated with Amphotericin-B.
• SUBCUTANEOUS ZYGOMYCOSES: Both come from insect-vectors and
amphibian shit. Both are prevalent with Diabetic Ketoacidosis.
o BASIDIOBOLUS RANIERUM: Amphibious excrement.
 Dissemination leads to
RHINOENTEROMOPHTOROMYCOSES. (See systemic
infections)
 Swelling of paranasal sinuses and face.
 Terrible swelling of the legs.
 Can be treated with KI.
o CONIDIOBOLUS CORONATUS:
 Leads to Subcutaneous MUCORPHYCOMYCOSES. Swelling
of legs.
 Can also be treated with KI.
• CHROMOMYCOSIS: Caused by infection with Phialophora and
Cladosporium.
o INFECTION: By direct skin-contact with fungus. It is tropical fungus
found in soil.
o MORPHOLOGY / DIAGNOSIS: Distinctive brown-pigmented hyphae
are found in culture.
o SYMPTOMS: Cutaneous lesions with no dissemination.
o TREATMENT: Difficult to treat.
• MYCETOMA: Infection with Petriellidium Boydii.
o INFECTION: Direct contact with bare feet.
o SYMPTOMS: Massive induration with draining sinuses. The rower who
insisted on rowing barefoot got this disease.
o TREATMENT: Difficult to treat.
OPPORTUNISTIC FUNGI:
• CANDIDA ALBICANS: Candida is dimorphic in that it exists in yeast and
hyphae form, but it is not thermally dimorphic.
o Morphology:

23.  YEAST: Candida in yeast form is part of our endogenous
mucocutaneous flora, and exists in healthy people in small
numbers in oral and vaginal mucosa.
 Psuedohyphae: This is also called germ-tubes. When Candida is
in the form of psuedohyphae, it can escape neutrophilic attack.
Other forms of Candida are susceptible to neutrophilic attack.
 HYPHAE: Candida only exists in hyphal state when it is
disseminated. In immunocompetent people, immunity keeps the
Candida in yeast state.
 Hyphae have extra and different adhesins which impart
virulence onto them.
 Hyphae are of the Ascomyces class.
o DEFENSE: Neutrophils are the most important defense. They can
phagocytose yeast form, and can release oxidative enzymes onto mycelial
form to degrade it.
 Neutropenia can thus lead to Candidiasis.
 Candida can bind iC3b receptors in a manner that inhibits
opsonization.
o CANDIDIASIS: Mucocutaneous Candida infection, originating from
endogenous flora.
 THRUSH: Oral Candidiasis on the tongue. White cheesy stuff.
Esophageal Candida can also be found.
 RISK FACTORS: AIDS, Diabetes
o DIAGNOSIS: KOH preparation, look for associated hyphae and the
disease is almost certainly Candidiasis.
o TREATMENT: Only Candida Albicans is susceptible to Fluconazole --
not other species.
 With AIDS, prophylactic use of Fluconazole leads to selection for
Non-Albicans species of Candida, and thus promotes disease of
other species.
• ASPERGILLUS FUMIGATUS:
o MORPHOLOGY: Characteristic finger-like conidia, and septate hyphae.
Hyphae are narrow and branch at narrow angles.
o AIR CONDITIONERS in hospitals can blow their conidia all over the
place when they are turned on initially. The Aspergillus can collect in
condensations around the air conditioner, and conidia are dispersed when
it's turned on.
o ALLERGY to Aspergillus is very common. Allergy is usually to the
galactomannans (against which we have antibodies) or glycoproteins.
 The extent of allergy is proportional to the dosage -- the amount of
Aspergillus hyphae present.
 Allergy is a pulmonary infection and occurs in lungs.
 IMMUNOGENICITY: Aspergillus conidia are not immunogenic.
It is not until hyphae are formed, and mycelia, that immune
response ensues.

24. o AFLATOXIN-B, found in moldy grain, is that awful carcinogen that
comes from Aspergillus.
o DISSEMINATED ASPERGILLOSIS: Septate Hyphae can disseminate
in immunocompromised host.
 Symptoms: Lung is most common site of immunocompetent and
immunocompromised infection.
 Acute Pneumonia is common in immunocompromised
patients.
 Bad prognosis with dissemination to other organs common.
 Causes
 Immunosuppression
 Feeding tube
 Use of an indwelling catheter
 Spread: Hyphae (not conidia) spread to all organ systems.
Dissemination is deadly and is often only detected post-mortem.
 IMMUNITY:
 Neutrophilic attack against the hyphal form is important in
initial protection.
 Aspergillus possess extracellular factors that inhibit
complement fixation by the alternative pathway.
• PNEUMOCYSTIS CARINII: Opportunistic organism of unknown origin. It
resembles both protozoa and fungi.
o It stains similar to fungi and shows evidence of ascus-like structures, but
cell walls like ergosterol.
o Due to no ergosterol, it is not sensitive to current anti-fungals.
• ZYGOMYCOSIS (MUCORMYCOSIS): Deadly infection of Rhino cerebrum
in immuno-compromised host.
o MORPHOLOGY: They are true molds and exhibit non-septate, broad
hyphae that branch approximately at right angles.
o PATHOPHYSIOLOGY: They like to grow in acidic environments or
immunocompromised hosts. They invade blood vessels, causing massive
infarcts.
 DIABETICS are especially vulnerable, since Ketoacidosis reduces
effectiveness of Neutrophils.
o Genera that cause it:
 Conidiobolus
 Basidiobolus
 Rhizopus (parasitic)
 Rhizomucor
 Absidia
 Mucor
 Cunninghamella
o Symptoms: Headaches ------> Orbital Cellulitis ------> Cranial Nerve
Palsy and hemorrhage ------> coma and death in 2 weeks if untreated.
• CRYPTOCOCCUS NEOFORMANS: See systemic infections.

25. Return to top
PARASITOLOGY
MALARIA (Plasmodium): A SPOROZOAN. The mosquito is the definitive host (in
which sexual reproduction takes place), and the human is the intermediate host, in which
larvae are disseminated.
• Species:
o PLASMODIUM FALCIPARUM: The most virulent of all of them. It will
attack all RBC's indiscriminately.
 Identification: Small rings on inside of cell; sometimes multiple
parasites inside each erythrocyte. Infected and uninfected
erythrocytes may or may not be the same size.
 The Schizont forms a ring or double-ring inside the
erythrocyte.
 Erythrocytic Cycle: 48 Hrs. -- infected erythrocytes rupture 48
hours after initial invasion into RBC.
 Malignant Tertian Malaria: It is the most virulent because it has
the shortest pre-erythrocytic cycle, and it produces the greatest
number of merozoites.
 PATHOGENESIS: Schizont in the RBC produces adhesins
that bind to ICAM-1, CD46, causing endothelial cell
adhesion.
 RBC LYSIS can also occur. This can result in anemia, and
if rapid, hemoglobinuria which is known as BLACK
WATER FEVER
o PLASMODIUM VIVAX
 Identification: Infected erythrocyte is pale, enlarged, and contains
dark pigment. This is because it attacks only immature (large
reticulocyte) RBC's.
 Erythrocytic Cycle: 48 Hrs. -- infected erythrocytes rupture 48
hours after initial invasion into RBC.
 14 to 16 merozoites are in each Schizont.
 Benign Tertian Malaria: Intermediate in severity. It can give
profound anemia after a week to a month.
o PLASMODIUM MALARIAE
 Identification: Infected erythrocytes are not enlarged and contain
no pigment.
 Erythrocytic Cycle: 72 Hrs. -- infected erythrocytes rupture 72
hours after initial invasion into RBC.
 Quartan Malaria: Slowest acting disease. After immunity is
formed, immune complexes can accumulate in the kidney.
 Only 8 Merozoites in each Schizont.

26. o PLASMODIUM OVALE
 Identification: Infected erythrocyte is pale, enlarged, and contains
dark pigment. This is because it attacks only immature (large
reticulocyte) RBC's.
 Erythrocytic Cycle: 48 Hrs. -- infected erythrocytes rupture 48
hours after initial invasion into RBC.
 Benign Tertian Malaria
• LIFE-CYCLE
o SEXUAL CYCLE: Sporogony in the mosquito, taking 1 to 3 weeks.
 Mosquito bites a malarious human and thereby ingests male and
female Plasmodium gametocytes.
 Zygote penetrates mosquito gut wall and forms an oocyst, in which
thousands of Sporozoites are grown.
 Oocyst ruptures, and thousands of SPOROZOITES are released
into mosquito, rendering it infectious to humans.
o ASEXUAL CYCLE: Schizogony, formation of the Schizont.
 Infected mosquito bites another human.
 PRE-ERYTHROCYTIC PHASE: It occurs in the liver.
 Sporozoites from mosquito's salivary glands make way to
human liver.
 Mosquito saliva has anti-coagulant properties.
 HYPNOZOITES: P. Vivax and P. Ovale: Some
sporozoites stay in hepatocytes and reside in a dormant
state.
 Sporozoites undergo asexual reproduction to make 2000 -
40,000 MEROZOITES.
 ERYTHROCYTIC PHASE: Formation of more Merozoites from
Merozoites.
 Merozoites (larvae) enter erythrocytes by receptor-
mediated endocytosis, where they mature to ring-shaped
TROPHOZOITES
 Erythrocytic Schizogony: The Trophozoite then
undergoes nuclear division to make multinucleated
SCHIZONT.
 Schizont then creates from 8 to 24 MEROZOITE daughter
cells.
 RBC's ruptures either 48 or 72 (P. Malariae) hours after infection,
releasing the merozoites to infect other cells, and effecting the
disease process.
 Some daughter cells will be transformed to gametocytes, where
they can be picked up by mosquitos.
• CLINICAL STAGES OF MALARIA:
o ACUTE: All organ systems can be involved. Hepatosplenomegaly, renal
failure, CNS vascular problems.
 P. Falciparum has the worst acute phase. P. Malaria has virtually
no acute phase.

27. o CHRONIC: Some immunity has been acquired, but there are still
organisms in the erythrocytic stage.
o RELAPSING: Re-activation of Hypnozoites of P. VIVAX and P. OVALE.
o RECRUDESCENT: Recurrent malaria due to immunodeficiency, such as
from corticosteroids, stress, or chemotherapy. This differs from relapsing
because the organisms did not come from the Hypnozoite stage, but rather
from an erythrocytic stage.
 Malaria is NOT a problem in AIDS.
PROTOZOA:
• GIARDIA LAMBLIA: FLAGELLATE INTESTINAL PROTOZOAN that lives
on the glycocalyx of intestinal enterocytes, causing Giardiasis.
o LIFE-CYCLE / MORPHOLOGY:
 Trophozoite form has two nuclei.
 Cyst form has four nuclei -- each cyst gives rise to two
trophozoites.
o INFECTION: Fecally contaminated food and water.
o PATHOPHYSIOLOGY:
 The creatures adhere to the enterocyte glycocalyx epithelium. This
leads to malabsorption and facilitates bacterial metabolism,
resulting in non-bloody diarrhea and immense foul-smelling
flatulence.
o TREATMENT: Flagyl (Metronidazole)
• CRYPTOSPORIDIUM PARVUM: FLAGELLATE INTESTINAL
PROTOZOAN which causes Cryptosporidiosis.
o INFECTION: Fecal-oral transmission.
o PATHOPHYSIOLOGY: It also affects the glycocalyx, living actually
intracellularly, between the apical plasma membrane and terminal web. It
never gets all the way into enterocytes though.
o CLINICAL: It leads to diarrhea. It is self-limiting in immunocompetent
people but is a problem in immunocompromised people.
• ENTAMOEBA HISTOLYTICA: RHIZOPOD that causes Amebiasis and is one
of the leading causes of DYSENTERY (bloody diarrhea).
o INFECTION / LIFE-CYCLE:
 Two stages -- Mobile stage, found in diarrheal stools, infects
humans, and non-mobile cyst stage that can be found in all stools.
 Cyst form has four nuclei.
 Can be transmitted as a cyst in food, or via anal / fecal - oral
transmission.
o PATHOPHYSIOLOGY:
 They initially invade in areas of fecal stasis (low peristalsis) -- the
cecum and recto-sigmoid colon. Trophozoites invade through the
intestinal epithelium where they can form flask-shaped ulcers in
the submucosa.

28.  The intestinal ulcers result in dysentery, or bloody diarrhea. If they
ulcerate all the way through, complications are Amebic Peritonitis
or Bacterial Peritonitis.
 Amoeba like to eat red cells. They get into the blood and go
through portal circulation to liver, where they form Liver
Abscesses that looks like anchovy paste.
o DIAGNOSIS: Take a fresh stool sample and look for motile trophozoites
in the stool. This finding is intermittent, and you should check at least
three times before ruling out amebiasis.
• TRICHOMONAS VAGINALIS: Pear-shaped, flagellate organism causes
Trichomoniasis, a sexually transmitted disease.
o LIFE-CYCLE: It exists only as a trophozoite -- no spore form.
o PATHOPHYSIOLOGY: Inhabits vagina or prostate.
o EPIDEMIOLOGY: Very common parasite, most common in sexually
active women in 30's.
o DIAGNOSIS: Women will have foul-smelling foamy discharge, itching,
and burning. Men are usually asymptomatic. Diagnose by wet-mount of
vaginal secretions.
o TREATMENT: metronidazole (Flagyl).
• TOXOPLASMA GONDII: The cause of Toxoplasmosis.
o INFECTION: Ingest cysts from undercooked meat or from contact with
cats. Person-to-person (horizontal) transmission does not occur, but
mother-fetus (vertical) transmission does occur.
 Tachyzoites: Organisms that rapidly multiply within
macrophages, to lyse the cell and infect other cells.
 Bradyzoites: In immunocompetent hosts, these are organisms that
slowly multiply within cysts, usually in the brain.
o DISEASE: The disease is usually asymptomatic in immunocompetent
host. Cell-mediated immunity is required to keep the disease
asymptomatic.
 Congenital Toxoplasmosis (TORCH): Occurs only when mother
is initially infected during pregnancy. If she was previously
infected, the disease won't reactivate.
 Infected newborns are symptomatic only 10% of the time.
Symptoms include encephalitis, chorioretinitis,
hepatosplenomegaly.
• TRYPANOSOMA:
o TRYPANOSOMA CRUZI: The cause of Chagas Disease (American
Trypanosomiasis)
 INFECTION: Vector is reduviid bug. Mammalian animals and
humans are both hosts.
 DISEASE: Organisms infects cardiac cells (cardiomyopathy), and
it causes neuronal damage leading to megacolon and
megaesophagus.
 Symptoms: Facial edema, and a nodule called chagoma,
fever, lymphadenopathy, hepato-splenomegaly.

29.  Death usually from cardiac failure or arrhythmias.
o TRYPANOSOMA BRUCEI (GAMBIENSE, RHODIENSE): The causes
of African Sleeping Sickness (African Trypanosomiasis).
 INFECTION: Tsetse fly is the vector. T. Gambiense infects
humans as host, while T. Rhodiense infects domestic animals and
humans.
 DISEASE: High antigenic variation in organisms leads to cyclic,
spiking fevers. Progressive demyelinating encephalitis, coma, and
death.
 Will see trypanosomal chancre at initial site of bite.
 T. GAMBIENSE is acute progress of disease (a few
months).
 T. RHODIENSE is chronic progress of disease (two years).
• LEISHMANIA:
o LEISHMANIA DONOVANI: Cause of Kala-Azar (Visceral
Leishmaniasis)
 INFECTION: Dayfly is the vector.
 DISEASE: Massive splenomegaly is characteristic finding, from
both proliferation of macrophages and sequestration of RBC's.
o LEISHMANIA BRAZILIENSIS: Cause of Mucocutaneous
Leishmaniasis.
 INFECTION: Vector = sandfly.
 DISEASE: Cutaneous lesion at site of bite with granulomatous
response.
NEMATODES (ROUNDWORMS):
• INTESTINAL NEMATODES can be remembered by the mnemonic AHEATS
o (A) ASCARIS LUMBRICOIDES: They are the largest intestinal
nematodes.
 INFECTION: Eating food contaminated with the eggs.
 LIFE-CYCLE: They subsist on ingested food and lay thousands of
eggs which pass through feces back to the soil.
 PATHOGENESIS / CLINICAL:
 Larval Migration is principle cause of disease -- they goto
lungs, inciting an Eosinophilic exudate in lungs. This can
lead to pulmonary ascariasis
 Intestinal ascariasis may be asymptomatic or may cause
pain or obstruction.
 DIAGNOSIS: Look for eggs in the feces.
 LOCATION: Worldwide, in USA found in the south.
o (H) HOOKWORMS -- ANCYLOSTOMA, NECATOR
 INFECTION: SKIN PENETRATION from filariform larvae in
moist soil. They then migrate to lungs, are coughed up, and then
are swallowed.
 PATHOGENESIS / CLINICAL:

30.  They develop into adults in small intestine and attach to
intestinal wall via hooking structures.
 Necator have cutting plates.
 Ancylostoma have teeth.
 Biggest clinical problem is BLOOD-LOSS -- Microcytic
Hypochromic Anemia, an iron-deficiency (not hemolytic)
anemia. The hookworms suck blood in small intestine.
 DIAGNOSIS: Look for eggs in the feces.
 LIFE-CYCLE: Fecal eggs yield Rhabditiform larvae which feed
but are not infectious to humans. They then mature into Filariform
Larvae which can penetrate human skin.
 LOCATION: Worldwide, in USA found in the south.
o (E) ENTEROBIUS VERMICULARIS -- PINWORM
 LIFE CYCLE: Strictly confined to humans.
 Male and female worms both live in colon.
 At night, female migrates to anus and lays eggs on the anus.
Reinfection of the eggs can then occur if the patient
scratches anus and then brings fingers near mouth (no wash
hands ick).
 The eggs form an allergenic goo, which is itchy, so
the patient scratches.
 INFECTION: Ingestion of eggs.
 CLINICAL: Perianal itching (pruritus) is most common
symptom.
 DIAGNOSIS:
 SCOTCH TAPE on the ass at night can recover eggs.
 The eggs are not found in stools. They are only found in
perianal region.
 Most commonly affects children.
o (A) ANISAKIS
 INFECTION: Raw saltwater seafood (sushi -- red snapper,
salmon), and dolphins and seals, leads to Anisakiasis.
 PATHOGENESIS: They penetrate gastric mucosa and dwell in
submucosa in stomach and intestine.
 SYMPTOMS: Gastroenteritis, eosinophilias, occult blood in stool.
o (T) TRICHURIS TRICHIURA -- WHIPWORM
 INFECTION: Eat food contaminated with the eggs.
 LIFE-CYCLE:
 Worms mate in colon, and thousands of eggs are created
daily.
 Embryos are formed only in warm, moist soil, after
defecation.
 CLINICAL: Most infections are asymptomatic. It may cause
diarrhea.
 TENESMUS is anal dry heaves. It can occur with
Whipworm and can lead to rectal prolapse.

31. o (S) STRONGYLOIDES STERCORALIS -- THREADWORM
 INFECTION / LIFE-CYCLE: Strongyloidiasis = Penetration of
skin by filariform larvae. They go to lungs, are coughed up and
then are swallowed.
 Larvae mature in small intestine, enter the mucosa, and lay
eggs.
 Eggs hatch within mucosa, forming Rhabditiform Larvae
 AMPLIFICATION CYCLE: Eggs can also form
more filariform larvae which can go back to the
lungs to repeat the cycle. This occurs particularly in
immunocompromised (AIDS) patients. It can be
fatal.
 CLINICAL: Can be asymptomatic, depending on worm-burden.
 Watery diarrhea
 Pneumonitis can occur in lung
 DIAGNOSIS: Identify larva in stool sample.
• TRICHINELLA is also a Nematode and causes Trichonosis which we get from
undercooked pork.
o PATHOGENESIS: Eggs develop in striated muscle cells.
o SYMPTOMS: Fever, muscle pain, eosinophilia, periorbital edema.
• TISSUE NEMATODES
o WUCHERERIA: Cause of Filariasis.
 INFECTION / LIFE-CYCLE: Female mosquito bites.
 Microfilariae are formed in the blood. They circulate in
the blood only at night, thus blood tests for the worm
should be taken at night.
 Microfilariae produce infective larvae which can be picked
up by another mosquito bite.
 CLINICAL: ELEPHANTIASIS, from lymph channel obstruction.
Gross enlargement of legs and genitals.
 Lymphangitis, cellulitis.
 DIAGNOSIS: Nighttime blood-smear for the microfilariae is
diagnostic.
o ONCHOCERCA: Cause of Onchocerciasis.
 INFECTION: Female blackfly bite. Microfilariae burrow in
subcutaneous tissue.
 CLINICAL: Subcutaneous pruritic papules and nodules that
ultimately migrate to eyes.
 Major cause of River Blindness
o LOA
o DRACUNCULUS
PLATYHELMINTHES CESTODES (TAPEWORMS): Has a scolex (head),
proglottids (segments), and suckers.
• TAENIA SAGINATA (BEEF TAPEWORM): Cause of Taeniasis.

32. o MORPHOLOGY: Scolex with four suckers.
 It has No Rostellum.
 Uterus proglottid has around 20 branches on each side.
o INFECTION: Ingestion of cysticerci in undercooked beef. Humans are
definitive host and cattle intermediate host.
o CLINICAL: Unlike pork tapeworm, findings are largely asymptomatic.
Proglottids may be found in stool.
• TAENIA SOLIUM (PORK TAPEWORM): Cause of Cysticercosis. It is called
cysticercosis because the larvae are pathogenic -- not the worm itself.
o INFECTION / LIFE-CYCLE: Undercooked pork. In pigs, they reside in
skeletal muscle (pig-meat).
 Normally, people ingest the larvae, or Cysticerci.
 REFLUX, as in vomiting, can expose proglottids to acid which
causes them to release tremendous numbers of eggs. Not good! A
far more dangerous, disseminated infection occurs once eggs are
released.
o MORPHOLOGY: It has 4 suckers a circle of hooks. Eggs look the same
as T. Saginata.
 It does have a Rostellum, hooks, coming out of scolex.
 Uterus proglottid has far fewer branches (5-10) on each side than
T. Saginata.
o PATHOGENESIS: Ingested larvae take 3 months to grow, and worms can
be up to 5m long.
 Intestinal tapeworm does little damage.
 The Cysticerci larvae cause the damage! They can go to brain
where they occupy space (non-inflammatory). Once they die,
inflammation can ensue.
 Neurocysticercosis is the leading cause of Epilepsy in Mexico,
where they eat undercooked pork.
• DIPHYLLOBOTHRIUM LATUM (FISH TAPEWORM): Cause of
Diphyllobothriasis.
o MORPHOLOGY: Worm has a sucking groove, and is the longest of
tapeworms, up to 13m.
o LIFE-CYCLE: Human are definitive hosts
 Copepod Crustacea are first intermediate host.
 Freshwater fish are second intermediate host.
o PATHOGENESIS: Largely asymptomatic.
 The worm likes to eat Vit B-12, thus Pernicious (Megaloblastic)
Anemia can result from infection.
 Abdominal discomfort and diarrhea may occur.
• ECHINOCOCCUS GRANULOSUS (DOG TAPEWORM): Cause of
Unilocular Hydatid Cyst Disease.
o LIFE-CYCLE: Dogs are definitive hosts, and so are sheep. Humans are a
dead-end intermediate host.
o EPIDEMIOLOGY: The disease is seen in big-game hunters and in
shepherds. Very large at-risk population.

33. o PATHOGENESIS: It more often infects sheep than humans.
 It forms one fluid-filled cyst that is just jam-packed with scoleces
from the parasite. Embedded daughter cysts can form within the
main cyst, etc.
 Cyst must be surgically removed. Parasite is antigenic, and if not
careful, removal of cyst and exposure to antigen can result in
anaphylaxis.
o SYMPTOMS: Often asymptomatic, but liver cysts, brain cysts can result.
Cyst rupture can cause fatal anaphylactic shock.
PLATYHELMINTHES TREMATODES (FLUKES):
• MORPHOLOGY: They possess sucking disks that provide them motion.
• ENTERIC FLUKES: Restricted to the orient and we will rarely see them.
o FASCIOLOPSIS BUSKI: Large enteric fluke -- very large, about size of
microscope slide.
 SYMPTOM: May cause intestinal obstruction. It will ruin the
brush border anywhere it sucks onto in the intestine.
o METAGONIMUS YOKOWSKI: Small enteric fluke.
• BILIARY (LIVER) FLUKES: They obstruct bile ducts and lay eggs within them,
leading to cholelithiasis (Gall stones).
o FASCIOLA HEPATICA: Relatively common large fluke.
 SYMPTOMS:
 Gallstones -- the eggs can be seeds for gallstones.
 Biliary obstruction can occur because the flukes are so
large. (High blood bilirubin glucuronide), biliary cirrhosis
if untreated.
 LIFE-CYCLE:
 Eggs are excreted in feces of infected host.
 Egg hatches and forms a miracidium in water. It penetrates
a SNAIL host.
 In snail, free-swimming cercariae are released. They
collect on watercress plants.
 Metacercariae are ingested by humans.
o FASCIOLA GIGANTICA: Relatively rare gigantic fluke.
o CLONORCHIS SINENSIS: Oriental SMALL BILIARY FLUKE,
causing Clonorchiasis.
 INFECTION: eating raw or undercooked freshwater fish.
 LIFE-CYCLE:
 Snails are first intermediate host.
 Eggs leave snail as free-swimming cercariae.
 Cercariae burrow in fresh-water fish, the second
intermediate host.
 EPIDEMIOLOGY: China, Japan, and Vietnam
 PATHOGENESIS: They get into the small bile ducts but don't
cause biliary obstruction except with a huge worm burden.

34.  They can lead to adenomatous hyperplasia, which
increases the risk for cholangiocarcinoma (carcinoma of
bile ductal epithelia).
o OPISTHORCHIS FELINEUS: SMALL BILIARY FLUKE, causing
Opisthorchiasis.
 CLINICAL: Very similar to Clonorchis infection.
 Infection can lay dormant for several years before
presenting clinically.
• BLOOD FLUKES: SCHISTOSOMA, which cause SCHISTOSOMIASIS
o LIFE-CYCLE / INFECTION: Snails are the intermediate host.
 Cercariae penetrate skin of human host, and are known as a
Schistosomula once inside.
 They immediately travel to liver, where they lay eggs. Male and
female mate in portal blood in liver.
 Female travels, against the flow of blood, to final destination (see
below) where it lays eggs.
 Eggs then reach fresh water again through feces, urine.
o Species Differentiation:
 SCHISTOSOMA MANSONI:
 Egg has a large lateral spine.
 Infects colon and resides in Inferior Mesenteric Venules.
 A cause of Hepatosplenic Schistosomiasis.
 SCHISTOSOMA JAPONICA:
 Egg has a small lateral spine.
 Infect small / large intestine and resides in Superior and
Inferior Mesenteric Venules.
 A cause of Hepatosplenic Schistosomiasis.
 SCHISTOSOMA HAEMATOBIUM:
 Egg has a terminal spine.
 Cause of Urinary Schistosomiasis.
 Reside in Vesicular Venous Plexus.
o PATHOLOGY: All pathological findings are due to the presence of the
eggs -- not the worms!
CLINICAL PRESENTATION of SCHISTOSOMIASIS
HEPATOSPLENIC URINARY
SCHISTOSOMIASIS SCHISTOSOMIASIS
Species Schistosoma Mancini Schistosoma Haematobium
Schistosoma Japonica
Pathogenesis Inflammatory granulomatous Inflammatory granulomatous
response to allergens from eggs response to allergens from eggs

35. in the colon in the bladder and lower
ureters.
ACUTE Eosinophilia Eosinophilia
SCHISTOSOMIASIS Granulomatous Polyps in Colon Hematuria
Fever, anorexia, weight loss, Terminal Dysuria (pain,
anemia difficulty at end of micturition)
Portal Hypertension
Secondary Sites of Eggs go back through portal Eggs go back through systemic
Infection circulation to liver, causing circulation (iliacs) to Lungs,
granulomatous inflammation in causing granulomatous
liver: Hepatomegaly, Liver inflammation in lungs.
tenderness
Sequelae Portal Hypertension leads to Obstructed urine flow results in
Splenomegaly, esophageal Hydroureter and
CHRONIC varices, and ascites. Malnutrition Hydronephrosis
SCHISTOSOMIASIS or concurrent GI infections can
result in death.
ACTIVE -vs- INACTIVE URINARY SCHISTOSOMIASIS: Inactive Schistosomiasis
refers to the remaining constriction and fibrosis of ureters that persists after infection has
subsided. It has similar symptoms to active Schisto, but it is not contagious.
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