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. Crown Root Enamel Dentin Gingival crevice Pulp Gingiva Alveolar bone
Figure 27.4
Enamel
Dentin
Crown
Gingival crevice
Pulp
Gingiva
Alveolar bone
Periodontal membrane
Root
Figure 27.4 Section through a tooth.
Bone marrow
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7. Figure 27.5 Figure 27.5 Microcolonies of bacteria.
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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 mm2
Day ,522 mm2
Figure 27.6 Distribution of dental plaque.
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10. Figure 27.7
Figure 27.7 Dental plaque.
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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. Major bacteria present Organ Major physiological processes
Figure 27.9
Esophagus
Major bacteria present
Organ
Major physiological processes
Prevotella
Esophagus
Streptococcus
Veillonella
Helicobacter
pH 2
Secretion of acid (HCl) Digestion of macromolecules
Stomach
Proteobacteria
Bacteroidetes
Actinobacteria
Fusobacteria
Duodenum
Enterococci
pH 4–5
Continued digestion Absorption of monosaccharides, amino acids, fatty acids, water
Lactobacilli
Small intestine
Jejunum
Bacteroides
Bifidobacterium
Clostridium
Ileum
Enterobacteria
Enterococcus
Escherichia
Figure 27.9 The human gastrointestinal tract.
Eubacterium
Large intestine
pH 7
Absorption of bile acids, vitamin B12
Klebsiella
Colon
Lactobacillus
Methanobrevibacter (Archaea)
Peptococcus
Peptostreptococcus
Proteus
Ruminococcus
Anus
Staphylococcus
Streptococcus
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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. Upper respiratory tract
Figure 27.11
Sinuses
Nasopharynx
Upper respiratory tract
Pharynx
Oral cavity
Larynx
Trachea
Lower respiratory tract
Figure The respiratory tract.
Bronchi
Lungs
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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. Highly virulent organism (Streptococcus pneumoniae)
Figure 27.14
Highly virulent organism (Streptococcus pneumoniae)
Moderately virulent organism (Salmonella enterica serovar Typhimurium)
100 80
Percentage of mice killed 60 40
Figure Microbial virulence. 20
101
102
103
104
105
106
107
Number of cells injected per mouse
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22. 27.6 Measuring Virulence Attenuation Toxicity
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 TOXICITY: toxin effects are local or systemic
Further exposure at local sites
TOXICITY: toxin effects are local or systemic
COLONIZATION and
GROWTH Production of virulence factors
TISSUE DAMAGE, DISEASE
EXPOSURE to pathogens
ADHERENCE to skin or mucosa
INVASION through epithelium
INVASIVENESS: further growth at original and distant sites
Further exposure
Figure Microorganisms and mechanisms of pathogenesis.
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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 Figure 27.15 Adherence of pathogens to animal tissues.
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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 Figure 27.16 Bacillus anthracis capsules.
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28. Figure 27.18
Figure Fimbriae.
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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
Figure Hemolysis.
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36. Out In Efflux of cytoplasmic components Cytoplasmic membrane
Figure 27.20
Efflux of cytoplasmic components
Cytoplasmic membrane
Out In
-Toxin pore
Influx of extracellular components
Figure Staphylococcal -toxin.
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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
Animation: Diphtheria and Cholera Toxins
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38. Normal protein synthesis Protein synthesis stops
Figure 27.21
Diphtheria toxin
Cytoplasmic membrane
Out In
Receptor protein
Diphtheria toxin
Amino acid
Figure The action of diphtheria toxin from Corynebacterium diphtheriae.
Ribosome
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. Normal Acetylcholine (A) induces contraction of muscle fibers
Figure 27.22
Excitation signals from the central nervous system
Muscle
Figure The action of botulinum toxin from Clostridium botulinum.
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
Tetanus toxin
Excitation signals from the central nervous system
Muscle
Normal Glycine (G) release from inhibitory interneurons stops acetylcholine (A) release and allows relaxation of muscle
Figure The action of tetanus toxin from Clostridium tetani.
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 Figure 27.24 The action of cholera enterotoxin.
Normal ion movement, Na from lumen to blood, no net Cl movement
Blood
Intestinal epithelial cells
Lumen of small intestine
GM1
Colonization and toxin production by V. cholerae
Cholera toxin AB form
GM1
Vibrio cholerae cell
Activation of epithelial adenylate cyclase by cholera toxin
A subunits
Cholera toxin B subunit
Adenylate cyclase
ATP
Cyclic AMP
Na movement blocked, net Cl movement to lumen
Figure The action of cholera enterotoxin.
Massive water movement to the lumen; cholera symptoms
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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 Figure 27.25 Limulus amoebocytes.
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