Medical microbiology

• humans and other mammals are sterile in utero, and are inoculated with microbes during passage through the birth canal
• Germ-free 'gnotobiotic' animals have defects in the intestinal epithelia and the immune system.
• isolator is the machine used to raise the germ free animals.
• human neonates are colonised primarily with facultative anaerobes.
• In the intestine at weaning obligate anaerobes emerge as key colonisers. At this time the intestinal epithelium dvelops an extensive capillary network, ensuring abundant blood supply. (correlation between bacteriode colonisation and intestinal blood vessel development.)
• By adulthood obligate anaerobes mainly bacteriodes predominate.
• inoculation of germ free mice with bacteriodes stimulates blood vessel development
• Immune system defects exhibited by gnotobiotic mice:

  • Higher susceptibility to infections
  • diminished cytokine levels
  • Reduced levels of innate immune cells
  • Reduced serum immunoglobulin levels
  • Reduced levels of CD4 t-cells
• Compared to conventionally raised mice, gnotobiotic mice have lower levels of splenic CD4 T cells
• colonisation of gnotobiotic mice with bacteirodes restores normal levels of CD4 t cells.
• Expansion of splenic CD4 T cells is caused by a bacterial capsular polysaccharide antigen termed PSA.
• CD4 t-cells activate macrophages and antibody producing B cells.
• Why are bacteriodes interaction mutualism?

  - for us it stimulates development of CD4 T cells

  -for them a host with a healthy immune system will be able to fight of infectious disease. Meaning longer host life longer life for the bacteriode community.
• compared to lean Obese individuals tend to have a higher proportion of firmicutes in their intestine.
• when obese people lose weight due to caloric restriction their proportion of bacteriodetes increased and firmicutes decreased
• bacteriodetes is the phylum containing the genus bacteriodes
• conventionally reared mice have a higher fat content than gnotobiotic mice.

  transplantation of the microbial community from conventional mice into gnotobiotic mice increased fat content.
• compared to lean mice, animals genetically predisposed to obesity have a decreased proportion of bacteriodetes and an increased proportion of firmicutes.
• innoculation of gnotobiotic mice with bacteria from obese donor mice results in greater fat content compared to with bacteria from lean mice.
• How might the microbial compostition of the intestine contribute to obesity?

  HYPO: The bacterial community in obese individuals may be more effecient in converting otherwise indigestible dietary polysaccharides into monosaccharides.
• Hepatic lipogenisis is the process that allows monosaccharides to be converted into fatty acids. this helps obese people get more energy from a meal.
• niches exclusion by commensals can protect against disease caused by pathogens
• Principle of niche exclusion: if two organisms are competing for the same resources, then one of those organisms will predominate. the other will dimish in number, and eventually disappear from that niche.
• Antibiotic-associated colitis is caused by anaerobic bacterium clostridium difficile.
• Antibiotic-associated colitis results when individuals is treated with antibiotics, (clindamycin, cephalosporins, or ampicillin. ) this is because AB treatment results in exptensive proliferation of C.difficile in the host's colon, resulting in production of bacterial toxins, and subsequent damage to the colonic mucosa. Causes diarrhea and a yellowish 'psuedomembrane' forms from dead host tissue.
• C.diff is an occasional coloniser of the gastrointestinal tract of healthy individuals,(2-5%) numbers to low to cause disease. IN hospitals up to 50% of patinets can be colonsied by C.diff in there intestine.
• Antibiotic treatment eliminates commensals.
• C.diff is thought to be resistant or poorly susceptible to killing by clindamycin, cephalosporins or ampicillin. other intestine colonisers are sensitive to these antibiotics.
• Vancomycin and metronidazole often resolve C.diff infections
• disease: injury that impairs host function
• pathogen: a disease-causing microorganism
• virulence (pathogenicity): the ability of a pathogen to cause disease
• Infection: growth of a pathogen in the host
• colonisation: multiplication of a microbe on or within host tissue or other surfaces
• koch's postulates

  1. the suspected pathogenic organism should be present in all cases of the disease and absent from healthy animals.
  2. The suspected organism should be grown in pure culture
  3. Cells from a pure culture of the suspected organism should cause disease in a healthy animal.
  4. the organism should be reisolated and shown to be the same as the original
• a possible 5th hypothesis?

  conditions that eliminates the pathogen from a patient or that decrease the infection rate in the general population should cure the disease or reduce its incidence.
• if all 4/5 postulates are satisfied, then this constitutes convincing proof that a disease is caused by a particular pathogen.
• Kochs postulates should not be considered an absolute prerequisite to providing evidence that a suspected pathogen causes disease. (technical limitations may preclude all postulates from being satisfied.)
• A limitation of kochs postulates is some pathogens cannot be purified this violate the second and fourth postulates.
• A limitation of kochs postulates is some diseases do not have an appropriate animal model this violates the third postulate.