MICROBES HUMANS

1. 27.1 Overview of Human–Microbial
Interactions
• Most microorganisms are benign
– Few contribute to health and fewer pose direct
threats to health
• Normal microbial flora
– Microorganisms usually found associated with
human body tissue
• Humans are colonized by microorganisms at birth
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2. 27.1 Overview of Human–Microbial
Interactions
• Pathogens
– Microbial parasites
• Pathogenicity
– The ability of a parasite to inflict damage on
the host
• Virulence
– Measure of pathogenicity
• Opportunistic pathogen
– Causes disease only in the absence of normal
host resistance
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3. 27.1 Overview of Human–Microbial
Interactions
• Infection
– Situation in which a microorganism is established
and growing in a host, whether or not the host is
harmed
• Disease
– Damage or injury to the host that impairs host
function
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4. 27.2 Normal Microflora of the Skin
• The skin is generally a dry, acid environment
that does not support the growth of most
microorganisms (Figure 27.2)
• Moist areas (e.g., sweat glands) are readily
colonized by gram-positive bacteria and other
normal flora of the skin
– Composition is influenced by
• Environmental factors (e.g., weather)
• Host factors (e.g., age, personal hygiene)
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5. 27.3 Normal Microflora of the Oral Cavity
• The oral cavity is a complex, heterogeneous
microbial habitat
• Saliva contains antimicrobial enzymes
– But high concentrations of nutrients near
surfaces in the mouth promote localized
microbial growth
• The tooth consists of a mineral matrix (enamel)
surrounding living tissue (dentin and pulp;
Figure 27.4)
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6. Figure 27.4
Enamel
Dentin
Gingival crevice
Pulp
Gingiva
Alveolar bone
Periodontal
membrane
Bone
marrow
Crown
Root
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7. Figure 27.5
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8. 27.3 Normal Microflora of the Oral Cavity
• Extensive growth of oral microorganisms,
especially streptococci, results in a thick
bacterial layer (dental plaque)
• As plaque continues to develop, anaerobic
bacterial species begin to grow
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9. Figure 27.6
Day 1 1436 mm2
Day 10 22,522 mm2
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10. Figure 27.7
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11. 27.3 Normal Microflora of the Oral Cavity
• As dental plaque accumulates, the
microorganisms produce high concentrations
of acid that results in decalcification of the
tooth enamel (dental caries)
• The lactic acid bacteria Streptococcus
sobrinus and Streptococcus mutans are
common agents in dental caries (Figure 27.8)
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12. 27.4 Normal Microflora of the
Gastrointestinal Tract
• The human gastrointestinal (GI) tract
– Consists of stomach, small intestine, and large
intestine
– Responsible for digestion of food, absorption of
nutrients, and production of nutrients by the
indigenous microbial flora
– Contains 1013 to 1014 microbial cells
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13. Figure 27.9
Major bacteria present Organ
Esophagus
Stomach
Small
intestine
Large
intestine
pH 2
Secretion of acid (HCl)
Digestion of macromolecules
pH 4–5
Continued digestion
Absorption of monosaccharides,
amino acids, fatty acids, water
pH 7
Absorption of bile acids,
vitamin B12
Duodenum
Jejunum
Ileum
Colon
Anus
Esophagus
Lactobacilli
Enterococci
Prevotella
Streptococcus
Veillonella
Helicobacter
Proteobacteria
Bacteroidetes
Actinobacteria
Fusobacteria
Bacteroides
Bifidobacterium
Clostridium
Enterobacteria
Enterococcus
Escherichia
Eubacterium
Klebsiella
Lactobacillus
Methanobrevibacter
(Archaea)
Peptococcus
Peptostreptococcus
Proteus
Ruminococcus
Staphylococcus
Streptococcus
Major physiological
processes
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14. 27.4 Normal Microflora of the
Gastrointestinal Tract
• Functions and Products of Intestinal Flora
– Intestinal microorganisms carry out a variety of
essential metabolic reactions that produce
various compounds
• The type and amount produced is influenced by
the composition of the intestinal flora and the diet
• Compounds produced include:
– Vitamins
– Gas, organic acids, and odor
– Enzymes
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15. 27.5 Normal Microflora of Other Body
Regions
• A restricted group of organisms colonizes the
upper respiratory tract
– Examples: staphylococci, streptococci,
diphtheroid bacilli, and gram-negative cocci
• The lower respiratory tract lacks microflora in
healthy individuals
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16. Figure 27.11
Sinuses
Nasopharynx
Pharynx
Oral cavity
Larynx
Trachea
Bronchi
Lungs
Upper
respiratory
tract
Lower
respiratory
tract
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17. 27.5 Normal Microflora of Other Body
Regions
• Urogenital Tract
– The bladder is typically sterile in both males and
females
– Altered conditions (such as change in pH) can
cause potential pathogens in the urethra (such
as Escherichia coli and Proteus mirabilis) to
multiply and become pathogenic
• E. coli and P. mirabilis frequently cause urinary
tract infections in women
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18. 27.5 Normal Microflora of Other Body
Regions
• The vagina of the adult female is weakly acidic
and contains significant amounts of glycogen
– Lactobacillus acidophilus, a resident organism in
the vagina, ferments the glycogen, producing
lactic acid
– Lactic acid maintains a local acidic environment
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19. 27.6 Measuring Virulence
• Pathogens use various strategies to establish
virulence (Figure 27.13)
• Virulence is the relative ability of a pathogen to
cause disease
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20. 27.6 Measuring Virulence
• Measuring Virulence
– Virulence can be estimated from experimental
studies of the LD50 (lethal dose50)
• The amount of an agent that kills 50% of the
animals in a test group
– Highly virulent pathogens show little
difference in the number of cells required to
kill 100% of the population as compared to
50% of the population
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21. Figure 27.14
Number of cells injected per mouse
101 102 103 104 105 106 107
100
80
60
40
20
Percentage
of
mice
killed
Highly virulent
organism
(Streptococcus
pneumoniae)
Moderately virulent
organism
(Salmonella enterica
serovar Typhimurium)
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22. 27.6 Measuring Virulence
• Attenuation
– The decrease or loss of virulence
• Toxicity
– Organism causes disease by means of a
toxin that inhibits host cell function or kills
host cells
• Toxins can travel to sites within host not
inhabited by pathogen
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23. Figure 27.13
EXPOSURE
to pathogens
ADHERENCE
to skin or mucosa
INVASION
through epithelium
COLONIZATION
and
GROWTH
Production of
virulence factors
TOXICITY:
toxin effects are
local or systemic
INVASIVENESS:
further growth at
original and distant sites
TISSUE
DAMAGE,
DISEASE
Further exposure
Further exposure at local sites
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24. 27.7 Entry of the Pathogen into the
Host – Adherence
• Specific Adherence
– A pathogen must usually gain access to host
tissues and multiply before damage can be done
– Bacteria and viruses that initiate infection often
adhere specifically to epithelial cells through
macromolecular interactions on the surfaces of
the pathogen and the host cell (Figure 27.15)
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25. Figure 27.15
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26. 27.7 Entry of the Pathogen into the
Host – Adherence
• Bacterial adherence can be facilitated by
– Extracellular macromolecules that are not
covalently attached to the bacterial cell surface
• Examples: slime layer, capsule
– Fimbriae and pili
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27. Figure 27.16
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28. Figure 27.18
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29. 27.6 Measuring Virulence
• Invasiveness
– Ability of a pathogen to grow in host tissue at
densities that inhibit host function
• Can cause damage without producing a toxin
• Many pathogens use a combination of toxins,
invasiveness, and other virulence factors to
enhance pathogenicity
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30. 27.7 Entry of the Pathogen into the
Host – Adherence
• Pathogen Invasion
– Starts at the site of adherence
– May spread throughout the host via the
circulatory or lymphatic systems
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31. 27.8 Colonization and Infection
• The availability of nutrients is most important in
affecting pathogen growth
• Pathogens may grow locally at the site of
invasion or may spread throughout the body
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32. 27.9 Invasion
• Pathogens produce enzymes that
– Enhance virulence by breaking down or altering
host tissue to provide access to nutrients
• Example: hyaluronidase
– Protect the pathogen by interfering with normal
host defense mechanisms
• Example: coagulase
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33. 27.10 Exotoxins
• Exotoxins
– Proteins released from the pathogen cell as it
grows
– Three categories:
• Cytolytic toxins
• AB toxins
• Superantigen toxins
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34. 27.10 Exotoxins
• Cytolytic toxins
– Work by degrading cytoplasmic membrane
integrity, causing cell lysis and death
• Toxins that lyse red blood cells are called
hemolysins (Figure 27.19)
• Staphylococcal a-toxin kills nucleated cells and
lyses erythrocytes (Figure 27.20)
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35. Figure 27.19
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36. Figure 27.20
Cytoplasmic
membrane
a-Toxin pore
Out
In
Influx of
extracellular
components
Efflux of
cytoplasmic
components
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37. 27.10 Exotoxins
• AB toxins
– Consist of two subunits, A and B
– Work by binding to host cell receptor (B subunit)
and transferring damaging agent (A subunit)
across the cell membrane (Figure 27.21)
• Examples: diphtheria toxin, tetanus toxin,
botulinum toxin
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Animation: Diphtheria and Cholera Toxins

38. Figure 27.21
Cytoplasmic
membrane
Diphtheria toxin
Amino acid
Ribosome
Diphtheria
toxin
Receptor
protein
Out
In
Normal protein synthesis Protein synthesis stops
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39. 27.10 Exotoxins
• Clostridium tetani and Clostridium botulinum
produce potent AB exotoxins that affect
nervous tissue
• Botulinum toxin consists of several related AB
toxins that are the most potent biological
toxins known (Figure 27.22); tetanus toxin is
also an AB protein neurotoxin (Figure 27.23)
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40. Figure 27.22
Excitation signals
from the central
nervous system
Muscle
Normal
Acetylcholine (A) induces
contraction of muscle fibers
Botulism
Botulinum toxin, , blocks
release of A, inhibiting contraction
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41. Figure 27.23
Inhibitory
interneuron
Inhibition
Excitation signals
from the central
nervous system
Tetanus
toxin
Muscle
Normal
Glycine (G) release from inhibitory
interneurons stops acetylcholine
(A) release and allows relaxation
of muscle
Tetanus
Tetanus toxin binds to inhibitory
interneurons, preventing release
of glycine (G) and relaxation
of muscle
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42. 27.10 Exotoxins
• Enterotoxins
– Exotoxins whose activity affects the small
intestine
– Generally cause massive secretion of fluid into
the intestinal lumen, resulting in vomiting and
diarrhea
• Example: cholera toxin (Figure 27.24)
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43. Figure 27.24
Blood Intestinal
epithelial
cells
GM1
Lumen of
small intestine
Normal ion movement, Na from lumen to blood,
no net Cl movement
Colonization and toxin production by V. cholerae
Activation of epithelial adenylate cyclase by cholera toxin
Na movement blocked, net Cl movement to lumen
Massive water movement to the lumen; cholera symptoms
Cholera
toxin
AB form
Vibrio
cholerae
cell
GM1
A subunits
Adenylate cyclase
ATP Cyclic
AMP
Cholera
toxin B
subunit
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44. 27.11 Endotoxins
• Endotoxin
– The lipopolysaccharide portion of the cell
envelope of certain gram-negative Bacteria,
which is a toxin when solubilized
– Generally less toxic than exotoxins
– The presence of endotoxin can be detected by
the Limulus amoebocyte lysate (LAL) assay
(Figure 27.25)
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45. Figure 27.25
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