Microbial Interactions with Humans

Normal microbial flora

Microorganisms that are usually found associated with healthy body tissue
Colonization
Growth of a microorganism after it has gained access to host tissues
Host
An organism that harbors a parasite
Parasite
An organism that grows in or on a host and causes disease
Pathogen
An organism, usually a microorganism, that causes disease
Outcome of host-parasite relationship depends on:
1) Resistance or susceptibility of host to parasite
2) Pathogenicity ability of a parasite to inflict damage on the host
3) The environment
Opportunistic pathogen
An organism that causes disease only in the absence of normal host resistance
Virulence
Quantitative measure of pathogenicity
Cell number that elicits disease in a host within a given time period
Infection
Any 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
Animal hosts provide favorable
environments for growth of
microorganisms
Rich in organic nutrients and growth factors
Provide conditions of controlled pH, osmotic
pressure, and temperature
Each region/organ a selective environment
Relative dryness of skin favors Staphylococcus aureus
High O
2
of lungs favors Mycobacterium tuberculosis
Low O
2
of intestine favors Clostridium genus
Infection starts at mucous membranes
Line the urogenital, respiratory, and gastrointestinal tracts
Consist of single or multiple layers of epithelial cells frequently coated with a protective layer of
viscous soluble glycoproteins called mucus
If microorganisms adhere to epithelial cell as a result of cell-cell recognition,
infection occurs
Figure 28.1 (Madigan et al. 2009)
Average adult has 2 m
2
of skin surface
Varies in chemical composition and moisture content
Most organisms associated with apocrine (sweat) gland secretions
Underarm, genital regions, nipples, and the umbilicus
Do not become fully functional until puberty
Figure 28.2 (Madigan et al. 2009)
Normal flora of skin (bacteria, fungi, yeasts) are either transients or residents
Residents are able to grow on skin, not merely survive like transient organisms

Most common and stable resident microorganisms are gram-positive Bacteria
Species of Staphylococcus and Streptococcus
Species of Corynebacterium
Propionibacterium acnes
Small numbers of gram-negative Bacteria
Escherichia and other intestinal organisms constantly inoculated onto skin via fecal contamination
Acinetobacter (non-fecal)
***Inability to compete with gram-positive Bacteria
What influences microflora composition on skin?
1) Weather
2) Age
3) Personal hygiene

Saliva is not an especially good growth medium for microorganisms
Nutrients in low concentration
Antibacterial substances
Lysozyme cleaves glycosidic bonds in peptidoglycan
Lactoperoxidase enzyme that kills bacteria

Structure of a tooth
Enamel mineral matrix of calcium phosphate crystals
Dentin and pulp living toot tissue
Figure 28.3 (Madigan et al. 2009)
Colonization
1) Attachment of single bacterial cells
Acidic glycoproteins from saliva form a thin organic film several micrometers thick attachment site
Streptococcus species
2) Formation of plaque
Thick bacterial layer resulting from colonization of glycoprotein film
3) As plaque continues to form, filamentous anaerobes begin to grow
Figure 28.4 (Madigan et al. 2009)
Bacteria in the mouth differ as humans age
What predominates and why?
In first year of life (no teeth present) aerotolerant anaerobes (i.e. streptococci and lactobacilli)
predominate
When teeth appear, balance of microflora shifts toward anaerobes
As plaque accumulates, microflora produce
high concentrations of organic acids that
cause decalcification
Diets high in sucrose promote dental caries
Lactic acid bacteria (Streptococcus sobrinus and
mutans) ferment sugar to lactic acid
Calcium phosphate is dissolved followed by
proteolysis of supporting matrix allowing bacteria to
penetrate further into matrix
Incorporation of fluoride into calcium
phosphate crystal tooth matrix increases
resistance to acid decalcification
Microorganisms in the mouth can also cause
gingivitis
Figure 28.5 (Madigan et al. 2009)
Figure 28.8 (Madigan et al. 2009)
Gastrointestinal tract consists of stomach, small intestine, and large intestine
Responsible for:
Digestion of food
Absorption of nutrients
Production of nutrients by indigenous microflora
Overall, there is about 10
13
to 10
14
microbial cells present in GI tract
Bacteria make up one-third the weight of fecal matter
Total number of bacterial cells shed per day is on order of 10
13
Passage of material through entire GI tract takes about 24 hours


Antibiotics inhibit growth not only of pathogens, but also normal microflora
Causes diarrhea
Allows opportunistic pathogens to establish in GI tract
Probiotics help to reestablish normal microflora
Respiratory tract
Upper respiratory tract
Nasopharynx, oral cavity, larynx, and pharynx
Staphylococci, streptococci, diptheroid bacilli, gram-negative cocci
Lower
Trachea, bronchi, and lungs
No resident microflora

Urogenital tract
Bladder
Sterile
Urethra
Colonized by facultative aerobic gram-negative rods and cocci (E. coli, Proteus mirabilis)
Pathogenesis
The ability of microorganisms to cause disease
Steps
1) Exposure to pathogen
2) Adherence to host cell
3) Invasion
4) Colonization
5) Growth
Result of unchecked growth
1) Toxicity
2) Invasiveness
***Both lead to host cell damage
Figure 28.12 (Madigan et al. 2009)
Ability of a pathogen to cause disease
Experimental studies of LD
50
Dose of agent that kills 50% of animals/cells in test
group
LD
50
for Streptococcus difficult to
determine because so few cells required to
kill 100% of population
LD
50
for Salmonella between 10
3
and 10
4
cells
Attenuation
Reduction or loss of virulence due to maintenance
in lab
Attenuated strains are used for production of
vaccines, especially viral vaccines
Figure 28.16 (Madigan et al. 2009)
Toxicity
The ability of an organism to cause disease by means of a preformed toxin that inhibits cell function or
kills host cells
e.g. Clostridium tetani produces tetanus toxin which initiates irreversible muscle contraction

Invasiveness
The ability of a pathogen to grow in host tissue in such large numbers that it inhibits host function
e.g. Streptococcus pneumoniae produces polysaccharide capsule that prevents the phagocytosis of
pathogenic strains, defeating host defense mechanism
Figure 28.17 (Madigan et al. 2009)
Virulence factors
Pathogen-produced proteins aiding in establishment and maintenance of disease
Enhance pathogen colonization and growth
e.g. streptococci, staphylococci and certain clostridia produce hyaluronidase
Enzyme that breaks down a polysaccharide functioning as intercellular cement, allowing spread from initial site of infection
1) Exotoxin
1) Cytolytic toxin
2) AB toxin
Two covalently bonded subunits; B generally binds to cell surface receptor; A transferred across membrane
3) Superantigen toxin
Stimulate large numbers of immune cells, resulting in extensive inflammation and tissue damage
Diptheria toxin
Tetanus and botulinum toxins
2) Enterotoxin
Cholera toxin
3) Endotoxin

Exotoxin
Proteins released from pathogen cell as it grows
1) Cytolytic toxins
Proteins that damage the host cytoplasmic membrane causing cell lysis and death
e.g. Hemolysins detected by growth on blood agar
Figure 28.18 (Madigan et al. 2009)
Exotoxin
Proteins released from pathogen cell as it grows
2) AB toxin
Inhibit protein synthesis
e.g. Diphtheria toxin, produced by Corynebacterium diptheriae
Figure 28.20 (Madigan et al. 2009)
Exotoxin
Proteins released from pathogen cell as it grows
2) AB toxin
e.g. Botulinum toxin, produced by Clostridium botulinum
Figure 28.21 (Madigan et al. 2009)
Exotoxin
Proteins released from pathogen cell as it grows
2) AB toxin
e.g. Tetanus toxin, produced by Clostridium tetani
Figure 28.22 (Madigan et al. 2009)
Enterotoxin
Exotoxins whose activity affects the small intestine
1) Cholera toxin, produced by Vibrio cholerae
Figure 28.23 (Madigan et al. 2009)
Lipopolysaccharides produced by gram-negative Bacteria as part of the outer layer
of their cell wall
Bound to cell wall and only released when cells are lysed
Found in E. coli, Shigella, and Salmonella
Risk factors for infection
Age
Stress and diet
Compromised host
Innate Resistance
Natural host resistance
Tissue specificity
If exposure site is not compatible with nutritional and metabolic needs of pathogen, no colonization
Physical and chemical barriers
Skin and mucosal tissues

Figure 28.25 (Madigan et al. 2009)