lec 12: Host microbe interactions and mechanisms of pathogenesis

Resident flora

fixed number and type of organisms

Transient Flora

inhibit organism for days/weeks/months. Do not establish permanent residence

Normal Flora roles

Aid in microbial antagonism. Disease prevention, and make compounds for host.

Streptococci entry into bloodstream

Endocarditis if valve artificial or defective

Bacteroides intestine rupture

released to peritoneal cavity and causes sepsis

E. coli outside of GI tract

UTI

Staphylococci entry into bloodstream

Serious problems with prosthetic implants

Bacteria on Skin

(S. epidermidis, S. aureus), (B. subtilis), (S. salivarius), (M. smegmatis), yeast and fungi in skin folds.

Bacteria in mouth and URI

Anaerobic staphylococci, gm(-) diplococci, diphtheroids and lactobacilli

Mouth and URI infections

Usually anaerobic bacteria. Periodontal infections, abscesses, sinusitis, and mastoiditis caused by Prevotella malaninogencia, fusobacterium, and peptostreptococci

Role of normal flora in dental cavities

S. sobrinus and S. mutans produce biofilm(plaque). They deteriorate enamel and proteases degrade dentin

Normal flora of Intestinal Tract

Not many bacteria are able to inhabit the acidic environment. Majority are obligate anaerobes 96-99%.

Normal flora of Genitourinary Tracts

Not many bacteria. Lactobacilli colonize birth canal soon after birth. group B hemolytic streptococci, prevotella, clostridia, listeria, and mobiluncus

Normal flora of the Eye

Not many bacteria. Small number of diphtheroids and some organisms native to the skin

Stages of Pathogenesis

Colonization→Evasion of immune system→Damage to Host

PATHOGEN

presence of organism abnormal, always causes disease (Yersinia pestis,
Mycobacterium tuberculosis)

Opportunistic Pathogen (2 classes)

Normally present in host can cause disease under unusual circumstances. Not normally present in host, only cause disease if immunocompromized.

Nonpathogen

Bacteria incapable of causing disease in specific host

Reservoir

Needed for pathogens to persist in the environment without a host. Sometimes living and either symptomatic or asymptomatic. Sometimes environmental such as bodies of water or in soil.

Vector

Vehicle of transmission for pathogens. Can be living(mosquitos) or Fomite(inanimate).

Infectious Process

First, the bacteria colonizes the host. They move to a tissue/organ suitable for multiplication. This site of proliferation varies between pathogens.

Clonal Nature of Bacterial Pathogens

Often traceable to a single organism or clone, but rare. Useful to determine the origin of an outbreak.

Regulation of Expression of Virulence Factors

They have mechanisms to regulate expression of virulence determinants. Several induce expression in host. Iron limitation, temperature shift, pH shift, Calcium limitation.

Virulence Factors - Adhesins

Assist in attachment. Some produce fimbriae that attach to surface carbohydrates on target cell. Some produce pili and they overcome the electrostatic repulsion.

Virulence Factors - Invasion

May invade phagocytic cell (Mɸ). Bacteria is engulfed and acidified by phagosome. Bacteria may survive. Fusion with lysosome destroyed most organisms. The bacteria can prevent this fusion and proliferate in the macrophage. Bacteria that cannot survive acidification will lyse the phagosome and escape before the fusion with a lysosome.

Invasion of non-phagocytic cells

Attachment→Type3 secretion. Secretion induces actin polymerization at site. Cell is forced to generate pseudopods and consume the organism. Escape through vacuole following invasion. Proliferation in cytoplasm of host.

Virulence determinants: Anti-phagocytic factors

Resistance to phagocytosis by PMNs and Mɸ. Expression of IgG Fc binding proteins on surface prevents opsonization. Some produce polysaccharide capsules which prevent phagocytic cell from attaching. Adhesins allow avid attachment to surfaces and prevent phagocytosis.

Virulence determinants: Enzymes

Hyaluronidase degrades hyaluronic acid which is a mahor component of connective tissue, allows penetration into tissues. Collagenase degrades collagen and allows deeper penetration into tissues. Streptokinase degrades fibrin clots. Coagulase promotes formation of fibrin clots. Hemolysin lyses RBC. Leukocidins lyse WBC.

Virulence determinants: Exotoxins

Two subunits A(active) and B(binding). B binds to receptor, A activates endocytosis. Aqueous channel created by B.

Diphtheria Toxin:

A gets into cytosol and catalyzes ADP ribosylation of Elongation factor 2.

Tetanus Toxin:

Affects nerve cells. Infects motor neurons then travels to brain stem. Inhibits signal to stop muscle contraction, induces rigid paralysis.

C. botulinum

produces botutoxin that targets motor neurons and induces flaccid paralysis. 10ng lethal dose. Most potent toxic known to man.

S. aureus

Toxic shock syndrome. Super antigen that stimulate production of cytokines. (IL-1 and TNFalpha). Rapid onset of system wide inflammatory response.

V. cholera

Initiates production of cAMP in epithelial cells of intestine. Flow of large amount of water and electrolytes into intestinal lumen. Fatal dehydration (23-30L water per day)

Virulence determinants: Endotoxins

Major component of Gm(-) cell wall. Not found in Gm(+). Found in the outer membrane. Endotoxin binds to receptors on macrophages and induces IL-1 TNFalpha and IL-6 production.

Iron Acquisition

Pathogens produce siderophores and bind iron with high affinity. Some use iron in RBC. Some use intracellular stores of iron within cells. Iron limitation increases expression of Virulence determinants and increases Ld50.