HTHSCI 2HH3 - Microbiology of Pathogenic Factors

normal flora

do not produce disease under normal conditions as long as it stays where it belongs, resident microbiota permanently colonize host, transient microbiota temporarily colonize the host

factors that determine distribution and compositions

nutrients, physical and chemical factors, mechanical factors, other “host” factors

nutrients

Secretory and excretory products of cells, bodily fluids, food in GI tract

physical and chemical factors

Temperature, pH, O2, CO2, salt, sunlight

mechanical factors

chewing, flow of saliva and peristalis of GI tract, mucous and ciliary action of respiratory system

other “host” factors

age, nutritional status, disability, stress, hygiene, lifestyle, geography, occupation

where are microbiota located?

upper respiratory tract, upper digestive tract, lower digestive tract, male and female urinary and reproductive systems, eyes and skin

microbial antagonism

normal flora benefits the host by preventing growth of pathogenic microbes as it competes with the pathogen for nutrients, produces substances harmful to the pathogen, and manipulates the host environment (increase or decrease pH and O2 levels)

microbial antagonism - E. coli in the gut

E. coli produces bacteriocins which are proteins that inhibit the growth of closely related species of bacteria like salmonella and shigella

How can infection/disease result?

when the balance between normal flora and a pathogenic microbe is altered (microbial antagonism fails). For example, large exposure to a pathogen

Factors that disrupt microbial balance

age, antibiotic use, changes in hygiene, nutritional status

microbial antagonism - C. diff

C. diff causes a range of GI symptoms from mild diarrhea to severe, or even fatal colitis, presence of normal flora in the large intestine inhibits the growth of C. diff (remains in endospore form). Antibiotic-mediated destruction of the GI normal flora creates an environment conducive to C. diff growth, resulting in disease

When do opportunistic infections occur

1. Microbes from the host normal flora move from their normal habitat, causing

disease

• Escherichia coli gains access to other body sites such as the urinary tract causing urinary tract infections

2. The host’s immune system is weakened/compromised - Pneumocystis jirovecii causes pneumonia in the immunocompromised patient, but has no effect on healthy individuals

3. Changes occur in the composition of the host normal flora

• Shift in the relative abundance of microbes (due to antibiotic therapy) creates opportunity for one species to thrive and cause disease

microbial mechanisms of pathogenesis (how pathogenic microorganisms cause disease)

contact/exposure, adherence, evasion of host defenses and penetration, damage of host cells, transmission

portals of entry

1. Mucous membranes

• Conjunctiva

• Upper respiratory (nose and mouth), gastrointestinal, and genitourinary tracts (placenta)

2. Skin

• When unbroken, the skin serves as an almost impenetrable barrier, however some bacteria can gain access to the body via natural openings in the skin (e.g., follicles, sweat gland ducts)

3. Direct deposition beneath mucous membranes or skin

• Trauma (punctures, wounds, cuts), surgery, invasive procedures, IV lines, broken skin, insect bites

what is the most common portal of entry?

upper respiratory tract from touching face and nose

adherence

• Means by which a pathogen attaches itself to host tissues at portal of entry

• Accomplished by cell surface molecules located on the pathogen called “adhesins” binding specifically to surface “receptors” located on the cells of host tissues

• Adhesins are host specific and tissue specific - there must be adhesin, Rc match

• Mechanisms of adhesion also contribute to the evasion of host defenses

• Use bacterial structures, adherence proteins, and glycocalyx

bacterial structures

• Adhesins are present on the fimbriae and flagella of many pathogenic bacteria

• P-fimbriae on pyelonephritogenic E. coli (kidney infection) adhere to a specific galactose dissaccharide found on the surface of uroepithelial cells, responsible for 90% of all urinary tract infections (UTIs)

adherence proteins

M proteins produced by Streptococcus pyogenes (GAS); appear as hair-like projections from the cell surface - mediates attachment of bacteria to epithelial cells of the host - many subtypes, some more strongly associated with specific diseases than others

glycocalyx

• If well organized and firmly attached to cell wall, referred to as a “capsule”

  • K1 capsule associated with strains of Neisseria meningitidis type B (most common circulating strain as vaccine is not widely administered and not covered under OHIP)

  • Binds to epithelial cells of the ventricles and vascular endothelium of the brain, causing meningitis

• If unorganized and only loosely attached to the cell wall, referred to as a “slime layer”

  • Facilitates the formation of biofilms

biofilms

• Colony of bacteria that adheres to surfaces (living and non-living) via a slime layer (glycocalyx)

  • Teeth, medical catheters, heart valves, hip replacement components, contact lenses, industrial food equipment, etc.

• May involve multiple bacterial species and consist of many layers antibiotics

• Contribute to chronic infections

• Shelters microorganisms from host defences; highly resistant to disinfectants and antibiotics - antibiotics can only kill most superficial layer therefore bacteria can continue causing infection

• Few treatments available, surgical intervention often required

If a pathogenic bacteria loses their ability to make adhesins they become …

avirulent

capsule

impairs phagocytosis, preventing phagocytic cell from adhering to the microbe, thereby increasing the virulence of the pathogen. With time, the host will produce antibodies against the capsule

bacterial species that possess a capsule are … virulent than those without

more; bacteria without a capsule can be easily dealt with most of the time

cell wall

• M proteins increase virulence by helping bacteria resist phagocytosis by WBC e.g., Streptococcus pyogenes

• Mycolic acid present in the cell wall of Mycobacterium tuberculosis increases virulence by helping the microbe resist digestion by phagocytes

• Streptococcus pneumoniae avoid destruction by host immune system by producing a capsule, which makes undetectable by the host immune system

coagulase

• Coagulate fibrinogen in the blood to form fibrin

• Fibrin clot protects the bacteria from phagocytosis, and isolates the microbe from other defenses of the host - clot made of own host material making it undetectable

• Produced by some Staphylococci spp. (coagulase + or - staph)

kinase

• Degrades fibrin, and thus digest clots formed by the body to isolate the wound and clots created by the bacteria as protection from phagocytosis (to get deeper into host tissues and wound)

• Streptokinase produced by Streptococcus pyogenes

• Staphylokinase produced by Staphylococcus aureus

How do coagulase and kinase faciliate a microbes’s ability to evade host defenses?

1. bacteria produce coagulase

2. clot forms protecting bacteria

3. bacteria later produce kinase, dissolving clot and releasing bacteria as well as facilitating microbe entry into host tissues

How are facultative intracellular bacteria able to survive in immune cells?

1. Escaping phagosomes before fusing with host cell lysosomes

2. Preventing phagosomes-lysosome fusion

3. Reducing effectiveness of toxic

   compounds within lysosome

4. Producing cell walls resistant to lysosomal proteases

disseminated infection

bacteria is able to leave portal of entry and travel elsewhere in the body

hyaluronidase

Degrades hyaluronic acid, a polysaccharide that holds host cells together, allows bacteria to penetrate deeper into host tissues

collagenase

Degrades collagen fibers at the base of superficial tissues and allows bacteria to move deeper into the host

How do hyaluronidase and collagenase help with penetration of host tissues?

1. invasive bacteria reach epithelial surface

2. bacteria produce hyaluronidase and collagenase

3. bacteria invade deeper tissues