Microbial Pathogenesis MMIC 7050

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Microbial PathogenesisMMIC 7050

• Course Coordinator Michelle Alfa
• Tel [phone]
• E-mail malfa_at_sbgh.mb.ca
• Website http//www.umanitoba.ca/faculties/medicin
  e/units/medical_microbiology/micropath2010_2011.ht
  ml

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Course Overview

• Selected current topics in Infectious Diseases
  Pathogenicity aspect
• Guided Self-study and Interactive learning
  experience (COME PREPARED!!)
• Each Block is 2 weeks (14 in total)-
  Overview lecture (1.5 2 hrs)- Student lecture
  (2 - 3/block, each 1 Hr)

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Learning Objectives

• Pathogenesis of Selected organisms
• Molecular basis of mechanisms
• Critique of models used
• Relate individual pathogens to block
  concept/theme
• Ultimately understanding of selected pathogens
  and common mechanisms of Host evasion used in
  disease process

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Grading System
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Process

• Approx 4 weeks before presentation, Presenters
  will be notified of topic by e-mail
• Key references provided on website
• Block lecturer overview prior to student
  presentations
• Student presentations powerpoint presentation
  and summary submitted by Monday noon? posted on
  website

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Student Presentation Guideline

• Oral presentation 40 minutes followed by 20
  minutes of discussion
• Written summary (6 pages max excluding figures
  and references)- provide summary of key info
• Grading scheme to be used by block lecturer (on
  website)

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POWERPOINT PRESENTATION
Student Topic Grading Scheme used by Block
Lecturer
POWERPOINT PRESENTATION
WRITTEN SUMMARY
TOTAL (100 marks maximum) ______________________
_____
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LECTURE SCHEDULE 2010-11
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(No Transcript)
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Plagiarism

• Ensure you know what is included in plagiarism -
  see U of M website- review Course outline
  material sent
• Reports Presentations- do not cut paste
  text from anywhere - do not use verbatim
  sentences from any reference source unless quoted
  using italics and reference source quoted.-
  acknowledge source for any pictures, figures,
  tables etc

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Class Input

• Ensure you notify me if you are going to a
  conference (I will try to ensure topic assignment
  does not clash)
• Volunteer Class Evaluations

• Select Topic sign name to a number on list to
  determine
• Topics for Presentation
• Topics for Take-home exam

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Natural Human Flora

• What organisms are part of normal flora
• Where do they colonize- microbial ecosystems
• How are they able to cause disease?- exposure-
  virulence factors

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Natural Flora Location
Log10 cfu/gm or cm2
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Sterile Body Sites
Central Nervous system (CNS)
Internal Abdominal Cavity all internal organs
Lungs
Bladder
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NORMAL FLORA
Mouth Upper Respiratory Tract
Streptococcus salivariusStreptococcus
mitisStaphylococcus epidermidisHaemophilus
speciesMoraxella speciesPeptostreptococcus
speciesFusobacterium speciesEikenella corrodens
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NORMAL FLORA
Mouth Upper Respiratory Tract
Enterobacteriaceae(E.coli, Proteus vulgaris,
Klebsiella pneumoniae, Enterobacter cloacae,
Serratia marcescens) Bacteroides fragilis,
etcClostridium perfringens, etcFusobacterium
speciesPeptostreptococcus speciesEnterococcus
species
Gastrointestinal Tract
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Human Gastrointestinal Tract

• Stomach pH 2.0, 102-103 cfu/ml
• Small Intestine pH 8.0, 104-108 cfhu/ml
• Colon pH 6-7, 1011 1012 cfu/ml

COLON- Anaerobes predominate - gt 500 bacterial
species - 75 of gut flora remain uncultured-
Firmicutes pylum (60 of gut flora) Gram
Positive with low GC content e.g.
Clostridium bartlettii, Ruminococcus spp,
Eubacterium spp,- Cytophaga-Flavobacterium-Bacter
oides (CFB) phylum ( 25 of gut flora)
Gram Negative
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Human Gut Microbiome

• Majority of bacteria in gut are uncharacterized
• Short Chain Fatty Acids (propionate, acetate,
  butyrate) from microbial fermentation supplies
  10 of host energy requirements)
• Imbalance in microbiome can lead to disease (e.g.
  C.difficile, Crohns, etc)
• Microbiome sequencing expanding our understanding

Duncan S, et al Cultivable bacterial diversity
from the human colon. Letters in Applied
Microbiology 200744343-350
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NORMAL FLORA
Mouth Upper Respiratory Tract
Lactobacillus speciesPrevotella
speciesPeptostreptococcus anaerobiusPorphyromona
s melaninogenicusYeast (e.g. Candida species)
Gastrointestinal Tract
Bacterial vaginosusimbalance in vaginal
microbiome
Genital Tract
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NORMAL FLORA
Mouth Upper Respiratory Tract
Staphylococcus epidermidisDiphtheroids
Corynebacterium speciesMicrococcus
speciesPropionibacterium species
Skin
Gastrointestinal Tract
Genital Tract
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Gram Stain Natural Flora

• Gram Positive cocci- Staphylococcus aureus -
  Staphylococcus epidermidis- Streptococcus
  pneumoniae
• Gram Positive bacilli- Corynebacterium
  species- Clostridium perfringens
• Gram Negative bacilli- Escherichia coli-
  Bacteroides fragilis
• Gram Negative cocci- Neisseria lactamica-
  Moraxella catarrhalis

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Microbes Human Disease A Dynamic Continuum

• Wicked Presence indicative of disease(e.g.
  M.tuberculosis, C.trachomatis, HIV)
• Waffler Dose Host affected(e.g.
  S.pneumoniae, N.meningitidis)
• Woosy Rarely harmful(e.g. Lactobacillus,
  Bacillus)

WICKEDWAFFLER.WOOSY
?NATURAL MICROBIAL FLORA?
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Global Causes of Death 1997
Principles and Practice of Infectious Diseases
5th ed 2000, Mandell (ed)
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Disease Burden in Humans
Principles Practice of Infectious Diseases 5th
Ed 2000, Mandell (ed)
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North America vs World!

• Canada- Malaria, TB, parasites, HIV rare-
  Pneumonia, UTI, wounds common
• Nigeria- Malaria, TB, parasites, HIV common-
  Pneumonia, UTI, wounds common

Geographic variation in infectious diseases-
climate vectors, - sanitation, - poverty-
healthcare support (e.g. availability of
vaccines, therapy etc),
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Reportable Organisms
Encephalitis Food poisoning Gonorrhea Hantavirus H
.influenza B invasive disease E.coli
O157H7 Hepatitis A,B,C,other Legionellosis Lepros
y Listeriosis Lyme Disease Measles Meningitis
(bacterial) N.meningitidis (invasive) WEE
AIDS/HIV Antrax Bacillus cereus Botulism Brucellos
is Campylobacter Chancroid Chlamydia Cholera C.per
fringens C.difficile Rubella (congenital) CJD Den
gue fever Diphtheria Viral hemorrhagic fever
Shigella MRSA Vanc R-S.aureus S.pyogenes
(invasive disease) Syphilis Tetanus Toxoplasmosis
Tuberculosis Tularemia Typhus Vibrio
parahemolyticus Yellow fever Yersinia
Parasites-various
Mumps Parapertussis S.pneumoniae Pen
Resistant Pertussis Plague Polio Psittacosis Q
fever Rabies Relapsing fever Rickettsial
disease Rocky Mountain Spotted fever Rubella Salmo
nella
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Bacterial Pathogens Isolates/year Diagnostic Lab

• Escherichia coli
  1637
• Staphylococcus aureus 1643
• Pseudomonas aeruginosa 716
• Staphylococcus epidermidis 690
• Klebsiella pneumoniae 414
• Enterococcus faecalis 833
• Haemophilus influenzae 156
• Bacteroides fragilis
  50
• Streptococcus pneumoniae 57

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Friend or Foe??!!
Throat Swab
Stool
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Studying Pathogenesis

• Human volunteers(Tuskegee experiment 1930s
  1940s)(H.ducreyi human arm model 1990s)
• Animal models(ID50, LD50 ), Molecular basis of
  damage
• In vitro models(tissue/organ culture, reactor
  vessels)- Molecular mechanisms

Relate Molecular Mechanisms back to Human
disease!!
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Disease Prevention??

• Host risk factors (avoidance)- travelers (boil
  it, peel it, uncap it)- unprotected Sex
• Treatment- antimicrobic- pro/pre biotics
• Vaccines

Normal Flora
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Summary

• Where do Natural Flora exist
• What organisms are considered Natural Flora
  (Gram stain and NameGenus species)
• Gut Microbiome role in health of host
• Natural Flora role in infection
• Issues related to prevention/treatment of
  infections due to Natural Flora

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MCQ

• Which one of the following bacteria is considered
  part of the Natural Flora in the Bladder?-
  Escherichia coli- Enterococcus faecalis-
  Bacteroides fragilis- None of the above

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MCQ

• Which one of the following bacteria is a Gram
  positive bacilli?- Escherichia coli-
  Cornebacterium species- Streptococcus
  pneumoniae- Staphylococcus aureus

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MCQ

• What one of the following is the phylum that
  represents the largest number of microbes in the
  colon?- Lactobacillus phylum-
  Cytophaga-Flavobacterium-Bacteroides (CFB)
  phylum- Firmicutes phylum- Enterobacteriaceae
  phylum

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Take Home Exam

• Questions will be derived from the student
  presentations