微生物学美国IndianaUniversityPurdueUniversity授课02

BIOL 533
11
Lecture Two
Physical & Chemical Aspects
• Important for sex hormones and bile salts
– Excreted through bile in conjugated form as glucuronides or sulfate, but cannot be reabsorbed in this form
BIOL 533
15
Lecture Two
Ecology of Normal Flora
• Parts of body colonized
– Contain small numbers, many in transit:
• Rest of respiratory and digestive tracts • Bladder • Uterus
– Bacteriodes from intestine into deeper
tissues as a result of trauma (or surgery) – Staphylococci from skin and nose – Streptococci and Gram— cocci from throat
– Serve as defense mechanism even in low concentration
– Bacterial stimulation leads to production of IgA that is secreted through mucus membranes
• Probably interfere with colonization of deeper tissues
• Lupus erythematosus—production of Ab against host DNA
– Some evidence that Ag may be cross-reacting bacterial LPS
• May cross-react with pathogen (meer from diarrhea due to overgrowth of yeasts, and staphylococci
BIOL 533
– Administration of clindmycin-Clostridium difficile (minor
member of normal flora) causes pseudomembranous
BIOL 533
6
Lecture Two
Immune Stimulation
• Sometimes antibodies elicited by normal flora cross-react with normal tissue:
– Antibodies against ABO blood group substances:
– Example: about 10% of population have meningococcus or pneumococcus as normal flora
BIOL 533
3
Lecture Two
Importance
• Opportunistic infections: normal flora in unusual sites; for example:
– Most are bacteria, but some are viruses, fungi, and protozoa
• We do not carry all of them all of the time • Each person has individualized normal flora
BIOL 533
2
Lecture Two
Normal Flora
• Some are found only on body; others also found in environment
• Problem: some people have transient normal flora (pathogens)
Medical Microbiology
Microbial Pathogenesis and Host-Parasite Relationships
BIOL 533 Lecture 2
BIOL 533
1
Lecture Two
Normal Flora
• General aspects
– Remember definition: organisms frequently found on or within body of healthy individuals
– Pneumocystis carinii (common inhabitant
of lung) causes pneumonia and death in AIDS patients
BIOL 533
5
Lecture Two
Immune Stimulation
• Antigenic stimulation by normal flora— do not have high antibody titers
BIOL 533
14
Lecture Two
Ecology of Normal Flora
• Parts of body colonized
– Contain large numbers:
• Skin • Respiratory tract (nose and oropharynx) • Digestive tract (mouth and large intestine) • Urinary tract (anterior parts of urethra) • Genital system (vagina) • Most are strict anaerobes
• A - make B antibodies • B - make A antibodies • O - make antibodies against both
– Why? Bacteria from intestinal flora contain Ag
that cross-react with both A & B blood substances
• Importance of carcinogen production not clear
BIOL 533
13
Lecture Two
Ecology of Normal Flora
• Use of germ-free animals
– Immune systems not well developed – Have to be fed vitamins
definitely indicate disease
– Blood – Cerebrospinal fluid – Synovial fluid – Deep tissues
BIOL 533
17
Lecture Two
Medical Microbiology
Strategies for Studying Microbial Pathogenesis
Lecture Two
Physical & Chemical Aspects
• Source of carcinogens
– Large intestinal flora
• Many potential carcinogens are only active after being modified
– Members of intestinal bacterial flora make glucuronidases and sulfatases that can deconjugate these compounds
• Physiological role not known
BIOL 533
12
BIOL 533
8
Lecture Two
Physical & Chemical Aspects
• Keeps out invaders
– Mechanisms:
• Physical advantage of previous occupancy • Some produce bacteriocins or antibiotics
colitis
10
Lecture Two
Physical & Chemical Aspects
• Role in human nutrition and metabolism
– E. coli and Bacteriodes synthesize vitamin K
– Metabolism of key compounds involves excretion from liver into intestine and their return to the liver
– Both endogenous and exogenous organisms can cause disease
• Infecting dose of Salmonella decreases one
million-fold when mice given streptomycin
• Patients treated with some potent antibiotics:
– Relevance to lab work: E. coli K-12 cannot
compete with intestinal flora
BIOL 533
9
Lecture Two
Physical & Chemical Aspects
• Antibiotic effects: wipes out normal flora
and mouth
BIOL 533
4
Lecture Two
Importance
• Depends on pathogen and on defenses
of host:
– Candida (yeast) causes pneumonia in
people undergoing cancer chemotherapy
1 Bacterium found in all patients having disease and it or its products found in all body parts affected
2 The bacterium should be isolated and grown in pure culture
BIOL 533
7
Lecture Two
Immune Stimulation
• Cross-reactivity does not normally cause disease
– Possible for antibodies cross-reactive to microbial Ag to cause problem
– Finding pathogens at these sites is
suggestive of disease, but not proof
BIOL 533
16
Lecture Two
Ecology of Normal Flora
• Sterile sites—pathogens in these
– Some modifications are carried out by enzymes of intestinal bacteria; example: cyclamate converted to bladder carcinogen (cyclohexamine) by bacterial sulfatases
BIOL 533 Lecture 2
BIOL 533
18
Lecture Two
Identification of Pathogens
• Traditional:
associate disease with organism
BIOL 533
19
Lecture Two
Koch’s Postulates