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Infection and Disease I

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The Normal Microflora of the Human Body Humans as Habitats Bodies are great places to be! Warm, stable, lots of nutrients available, constant pH and osmotic pressure ... – PowerPoint PPT presentation

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Title: Infection and Disease I


1
Infection and Disease I
  • The Normal Microflora of the Human Body

2
Humans as Habitats
  • Bodies are great places to be!
  • Warm, stable, lots of nutrients available,
    constant pH and osmotic pressure, etc.
  • Our bodies are not uniform environments, though
  • Each region or organ differs skin, GI tract,
    respiratory tract, etc. provide different
    conditions
  • Animals possess great defense mechanisms
  • The successful colonizers (and the successful
    pathogens -- more on this next lecture) are those
    that can get around these defenses
  • Normal doesnt mean non-pathogenic we
    sometimes have pathogens (S. pyogenes, S. aureus,
    etc.) in low numbers in and on us

3
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 environment.

Bacteria may associate loosely or firmly Breaches
in the mucosal barrier can result in infection
(pathogenesis)by opportunistic pathogens
4
How we get our indigenous microflora?
  • Normally, a human fetus has no resident
    microorganisms
  • Initial colonization comes during breaking of
    fetal membranes and, especially, birth itself.
  • Environment in general is colonization source
    mother, father, doctor, etc. Can vary by wards.
  • Initial microflora depends on whether infant is
    breastfed or not. Bifidobacterium vs. others.

5
Effects of breastfeeding vs. bottle-feeding on
indigenous microflora
  • 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 lower pH and less
    buffering capacity in large intestine. This
    disfavors enterobacteria and favors
    Bifidobacteria.
  • Bifidobacterium seem to compete with potential
    pathogens like Clostridium difficile and some
    enterobacteria
  • One study demonstrated that bottle-fed infants
    were 4X as likely as breastfed ones to harbor C.
    difficile.

6
Normal flora of specific regions
  • Skin
  • Oral cavity
  • Gastrointestinal tract
  • Other areas
  • Upper respiratory tract
  • Lower respiratory tract
  • Urogenital tract
  • Microorganisms are normally not found in the
    organs, blood, or lymph. (if they are, youre in
    trouble!)

7
Normal flora of the skin
  • Skin surface is unfavorable habitat.
  • Usually only populated by transient microbes
  • Exceptions are moister areas scalp, face, ears,
    underarms, genitourinary, palms, toes.
  • Most resident skin microorganisms inhabit deeper
    layers of the epidermis, sweat glands, and
    follicles.
  • Most of the residents are Gram-positives,
    especially Staphylococcus and Propionibacterium

8
Normal flora of the skin (cont.)
  • The dermis and subcutaneous tissue are normally
    sterile

9
Normal flora of the skin (cont.)
  • Microorganisms are primarily associated with
    glands
  • 1) Eccrine glands
  • Widely distributed
  • Main glands for perspiration secrete a hypotonic
    saline solution with a variety of organic and
    inorganic substances
  • Relatively devoid of microorganisms, probably due
    to salinity and low pH
  • 2) Apocrine glands
  • Restricted to underarms, genitals, etc.
  • Dont develop before puberty
  • Apocrine sweat has higher pH than eccrine sweat
  • Population numbers can be high
  • 3) Sebacious glands -- associated with hair
    follicles
  • Produce sebum, chief component of skin lipids
  • These lipids have antibacterial activity, esp.
    against Gram-positive cocci.

10
  • Common Skin Bacterium May Be New Opportunistic
    Pathogen
  • (A.H. Chagla, A.A. Borczyk, R.R. Facklam, and M.
    Lovgren. 1998. Breast abscess associated with
    Helocococcus kunzii. Journal of Clinical
    Microbiology. 362377-2379.)
  • 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.

11
  • 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 email
    Dr. Gutensmell. Enjoy April Foolery.

12
Normal flora of the mouth
  • A great place to live! (in contrast to the skin)
  • The only negatives salivary enzymes (lysozyme
    and lactoperoxidase), and constant need to
    re-attach
  • Initially (i.e. at birth), there are only a
    limited number of bacterial types (aerotolerant
    anaerobes like Lactobacillus and Streptococcus),
    then as teeth erupt there are more anaerobes and
    bacteria adapted to living in crevices and on
    smooth surfaces.

13
Biofilm (plaque) formation
  • Begins as thin film of glycoproteins in saliva
  • This is colonized (quickly) by individual
    Streptococcus (S. mutans, etc.) cells, which grow
    to microcolonies
  • Extensive growth of these results in formation of
    a thick biofilm. Further colonization can include
    filamentous forms, spirochetes, and various
    anaerobes.

14
  • Scanning electron micrograph of dental plaque.
    The many different kinds of bacteria composing
    the plaque exhibit specific attachments to the
    tooth and to each other

15
  • Plaque accumulates calcium salts to form tartar

16
  • Scale magnified 7,000x to show imbedded
  • bacterial biofilm

http//www.buckman.com/eng/biofilm3.htm
17
Normal flora of the GI tract
  • The body is like a donut, with the alimentary
    canal the inside of the donut. Things inside
    the alimentary canal are not truly inside the
    body

18
Normal flora of the GI tract (cont.)
19
Stomach
  • pH of stomach is low, around 2
  • Acts as a microbiological barrier
  • Bacterial count of stomach contents is low, but
    walls can be heavily colonized.
  • Primarily Lactobacillus and Streptococcus

20
  • 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

21
Helicobacter pylori, cause of stomach ulcers
22
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. 1999. Journal of Clinical
Microbiology. 37 2456-2460.)
23
Normal flora of the GI tract (cont.)
  • The upper portions of the small intestine are
    acidic and resemble the stomach. The lower
    portions have increasing numbers of bacteria,
    from 105 to 107 per gram.
  • The large intestine has enormous numbers of
    bacteria, 1010 to 1011 cells/gram! Is essentially
    a fermentation vessel.

24
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25
Why dont 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 http//www.sciencemag.org/cgi/content/full/289
    /5484/1483

26
Normal flora of other places
  • Urogenital tract -- bladder usually sterile but
    urethra epithelium colonized by facultative
    Gram-neg. rods like E. coli. These can become
    opportunistic pathogens.

27
  • Upper respiratory tract -- Staphylococcus,
    Streptococcus, diphtheroid bacilli, Gram-neg.
    cocci. Also some pathogens
  • Lower respiratory tract -- essentially sterile
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