Infection and Disease I. Humans as Habitats
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1 1 Infection and Disease I The Normal Microflora of the Human Body Bodies are great places to be! Humans as Habitats Warm, stable, lots of available, constant ph and osmotic pressure, etc. Our bodies are not, though Each region or organ differs: skin, GI tract, respiratory tract, etc. provide different conditions Animals possess great mechanisms The successful colonizers (and the successful pathogens -- more on this next lecture) are those that can get around these defenses Normal doesn t mean non-pathogenic; we sometimes have (S. pyogenes, S. aureus, etc.) in low numbers in and on us
2 2 Humans as Habitats (cont.) Colonization (and infection) frequently begin at mucous membranes These are found throughout the body. Consist of single or multiple layers of epithelial cells, tightly packed cells in direct contact with the external. Bacteria may associate loosely or firmly Breaches in the barrier can result in infection (pathogenesis)by opportunistic pathogens How we get our indigenous microflora? Normally, a human fetus has no microorganisms Initial colonization comes during breaking of fetal and, especially, birth itself. in general is colonization source: mother, father, doctor, etc. Can vary by wards. Initial microflora depends on whether infant is or not. Bifidobacterium vs. others.
3 Effects of breastfeeding vs. bottle-feeding on indigenous microflora 3 Large effect seen -- breastfed infants develop primarily Bifidobacterium populations, bottle-fed get a mixture of various species of coliforms, Clostridium, Staphylococcus, Streptococcus, Lactobacillus, etc. Breastfed infants have and less capacity in large intestine. This disfavors enterobacteria and favors Bifidobacteria. Bifidobacterium seem to with potential pathogens like Clostridium difficile and some enterobacteria. One study demonstrated that bottle-fed infants were X as likely as breastfed ones to harbor C. difficile. Skin Oral cavity Normal flora of specific regions (outline) Gastrointestinal tract Other areas Upper respiratory tract Lower respiratory tract Urogenital tract Microorganisms are normally not found in the organs,, or lymph. (if they are, you re in trouble!)
4 4 Normal flora of the skin Skin surface is unfavorable habitat. Usually only populated by transient microbes Exceptions are areas: scalp, face, ears, underarms, genitourinary, palms, toes. Most resident skin microorganisms inhabit layers of the epidermis, sweat glands, and follicles. Most of the residents are Gram-, especially Staphylococcus and Propionibacterium Normal flora of the skin (cont.) The dermis and subcutaneous tissue are normally.
5 5 Normal flora of the skin (cont.) Microorganisms primarily associated with glands: 1) Eccrine glands Main glands for Widely distributed Relatively of microorganisms, probably due to extensive 2) Apocrine glands Restricted to underarms, genitals, etc. Don t develop before Population numbers can be high 3) Sebacious glands -- associated with Common Skin Bacterium May Be New Opportunistic Pathogen (A.H. Chagla, A.A. Borczyk, R.R. Facklam, and M. Lovgren Breast abscess associated with Helocococcus kunzii. Journal of Clinical Microbiology. 36: ) A usually harmless bacterium, commonly found on human skin, may be an emerging opportunistic pathogen, say researchers from the London Public Health Laboratory; the Central Public Health Laboratory of Toronto; the National Center for Streptococcus in Edmonton, Alberta, Canada; and the U.S. Centers for Disease Control and Prevention. They report a case of infection by this organism the August 1998 issue of the Journal of Clinical Microbiology. Helococcus kunzii is a recently identified bacterium that is thought to be a nonpathogenic member of normal human skin flora and is rarely associated with skin infections. In the study though, the researchers report the isolation of the organism from an infected cyst on the breast of a 57-year-old immunocompromised woman. "Our finding provides further support for the opportunistic role of H. kunzii in causing infection in both immunosuppressed and immunocompetent patients," say the researchers.
6 6 Aromabacter malodorens is the bacterium that colonizes healthy human skin. This organism grows on sweat and produces butyrate and other organic acids which smell bad in high concentrations. This past year, scientists affiliated with the International Society for Microbial Ecology created a genetically engineered strain of this microorganism that can help banish unpleasant underarm odor. Scientists removed the butyrate synthase gene that causes one of the unpleasant odors. Scientists then inserted the DNA from an Asian Musk Deer that encodes muskolic acid. Muskolic acid is the compound that gives musk oil its characteristic smell. In preliminary studies, this new strain of Aromabacter malodorens survives well on the human skin. Scientists are now working on ways for the genetically engineered bacteria to out compete native populations of foul-smelling bacteria. The ISME plans to market an underarm deodorant containing these new bacteria and license this technology to other deodorant manufacturers. Because the deodorant is self-replicating, it requires only monthly application. If this microorganism sells well, the ISME plans to genetically engineer a mint-flavored bacterium for the mouth. If you would like more information or would like to participate in a deodorant trial, please Dr. Gutensmell. Enjoy April Foolery. Normal flora of the mouth A great place to live! (in contrast to the skin) The only negatives: salivary (lysozyme and lactoperoxidase), and constant need to. Initially (i.e. at birth), there are only a limited number of bacterial types (aerotolerant anaerobes like Lactobacillus and Streptococcus), then as erupt there are more anaerobes and bacteria adapted to living in and on smooth surfaces.
7 7 Biofilm (plaque) formation Begins as thin film of glycoproteins in This is colonized (quickly) by individual (S. mutans, etc.) cells, which grow to microcolonies Extensive growth of these results in formation of a thick. Further colonization can include filamentous forms, spirochetes, and various. Scanning electron micrograph of dental plaque. The many different kinds of bacteria composing the plaque exhibit specific to the tooth and to each other.
8 8 Plaque accumulates calcium salts to form tartar Ca 3 (PO 4 ) 2 scale (tartar) from human tooth Scale magnified 7,000x to show imbedded bacterial
9 9 Normal flora of the GI tract The body is like a, with the alimentary canal the inside of the donut. Things inside the alimentary canal are not truly inside the body Normal flora of the GI tract (cont.)
10 10 Stomach ph of stomach is low, around Acts as a microbiological Bacterial of stomach contents is low, but walls can be heavily. Primarily Lactobacillus and Streptococcus Gram-stained preparation of the stomach wall of a 14-day old mouse, showing extensive development of lactic acid bacteria in association with the epithelial layer
11 11 Helicobacter pylori, cause of stomach Infection with Helicobacter pylori, the bacteria responsible for peptic ulcers, may be transmitted via the hands In the study, researchers analyzed H. pylori infections in a small, rural population in Guatemala, testing blood samples, oral samples and samples from underneath the fingernails. They found that over half of the subjects tested positive via blood test, nearly 90 percent tested positive for oral carriage of the infection and over half tested positive for fingernail carriage. "Helicobacter pylori infection remains one of the most common in humans, but the route of transmission of the bacterium is still uncertain," say the researchers. "The results of this study suggest that oral carriage of H. pylori may play a role in the transmission of infection and that the hand may be instrumental in transmission. (S.A. Dowsett, L. Archila, V.A. Segreto, C.R. Gonzalez, A. Silva, K.A. Vastola, R.D. Bartizek and M.J. Kowolik Journal of Clinical Microbiology. 37: )
12 12 Normal flora of the GI tract (cont.) The upper portions of the small intestine are and resemble the. The lower portions have increasing numbers of bacteria, from 10 5 to 10 7 per gram. The large intestine has enormous numbers of bacteria, to cells/gram! Is essentially a fermentation vessel.
13 13 Why don t all these commensal bacteria produce a constant and massive inflammation of the GI tract epithelial cells? A recent study published in the journal Science indicates that the normal flora apparently shuts off the inflammation response in host epithelial cells See Normal flora of other places Urogenital tract -- bladder usually but epithelium colonized by facultative Gramneg. rods like E. coli. These can become opportunistic pathogens.
14 14 Upper respiratory tract -- Staphylococcus, Streptococcus, diphtheroid bacilli, Gram-neg. cocci. Also some pathogens Lower respiratory tract -- essentially
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