Title: Infection and Disease I
1Infection and Disease I
- The Normal Microflora of the Human Body
2Humans 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
3Humans 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
4How 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.
5Effects 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.
6Normal 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!)
7Normal 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
8Normal flora of the skin (cont.)
- The dermis and subcutaneous tissue are normally
sterile
9Normal 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.
12Normal 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.
13Biofilm (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
17Normal 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
18Normal flora of the GI tract (cont.)
19Stomach
- 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
21Helicobacter pylori, cause of stomach ulcers
22Infection 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.)
23Normal 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.
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25Why 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
26Normal 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