Download medmicro1-intro normal flora

Medical Microbiology
SBM 2044
Assoc Prof Dr Othman Abd Samah
Tel
: 09-5716744
Email : [email protected]
Sr. Intan Azura Shahdan
Tel
: 09-5716400 ext 2816
Email : [email protected]
SBM 2044 LECTURE 1
INTRODUCTION TO MODULE
Value: 4 credit hours
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Methods of assessment
Module Aims & Objectives
Course structure, Reading, etc.
Introduction – Recall some foundations
from Principles of Microbiology SBM 2053
SBM 2044: Aims
To foster knowledge and understanding of certain
microbial pathogens, selected to illustrate:
• various kinds of host-pathogen interactions
• experimental approaches used to study
bacterial/viral pathogens
• molecular mechanisms in bacterial pathogenicity
• clinical diagnosis and treatment
Course Content
• Microbes – Man interactions
Week 1-3
• Medical Bacteriology
Week 4-6
• Medical Virology & Biological Agents of
Warfare
Week 7-10
• Medical Mycology
Week 11-12
• Emerging infectious diseases
Week 13
• Introduction to the diagnosis and treatment
of infection
Week 14
Microbes – Man interactions
Lecture 1:
• Why is this subject important?
• The normal human flora
• Factors influencing bacterial-host interactions
Lecture 2:
• Introduction to bacterial pathogenesis
Lecture 3:
• Weapons delivery and deployment
Today
1. How do we recognise pathogens?
Only a tiny proportion of all known microbes cause
disease
2. How do we identify a particular microbe as the
cause of a particular disease?
3. Which microbes cause disease?
4. How do they do it?
5. How do we stop them?
6. How do we identify a particular microbe as the cause of
a patient’s illness?
Deaths in children (0 – 4 years) in 1998
Injury
Various Noncommunicable
Perinatal
Nutritional
6% 3%
INFECTIOUS
DISEASE
8%
20%
63%
Data from WHO 1999
Vineeth, 7 months old
and identified as HIVpositive, cries at the
Community Health
Education Society
orphanage in Madras,
India.
The WHO
estimates 800,000
children were
infected with HIV in
2001 alone, almost
all through motherto-child
transmission.
Premature deaths (0 – 44 years) in 1998
Maternal
Perinatal
Nutritional
3% 2%
10%
INFECTIOUS
DISEASE
48%
18%
19%
Various noncommunicable
Injuries
Data from WHO 1999
Human priorities ?
Deaths 1945 – 1993
(in millions)
Spending 1995
(in billions $)
AIDS + Malaria + TB
War
15
23
150
AIDS + Malaria + TB
864
Military
Malaysian Facts
• Population: 24,821,286 (July 2007 est.)
• Death rate: 5.05 deaths/1,000 population
(2007 est.)
• HIV/AIDS (2003 est.) –
– adult prevalence rate:
0.4%
– people living with HIV/AIDS: 52,000
– HIV/AIDS - deaths:
2,000
• REFERENCE: www.cia.gov/library
How do we identify a particular microbe
as the cause of a particular disease?
• The Koch Henle postulates
1. Isolate the organism from every case
2. Propagate in pure culture in vitro
3. Reproduce disease by injecting the organism
into a suitable recipient
4. Re-isolate the organism
• OK for major acute diseases like plaque,
smallpox, typhoid..
• Pathogens vs. non-pathogens: the Normal
Flora
– Only a minute fraction of the organisms in the
environment cause disease.
• Isolation of an organism from a patient
does not imply disease.
– many different forms of association between
microbes and humans
– many yet unknown, non-culturable eg. In soil,
water, extreme environments
– Others colonise other living organisms,
virtually all multicellular organisms have their
own normal flora, organisms with which they
coexist.
Factors controlling growth
1. Nutrient availability
 Essential elements:
• Major: C, O, H, N, S, P, K, Mg, Ca, Fe, Na, Cl
• Minor: Zn, Mn, Co, Cu
 All present in vivo, but all not readily available
to infecting bacteria – e.g. Fe
• Concentration in plasma ca. 20µM
• Freely available: 10-18M
 Pathogens
• All heterotrophic (need organic C source)
• Many fastidious
Factors controlling growth
2. Physical environment
 Water activity (aw) - not limiting in vivo
 Osmotic pressure (π) - moderate/high
• Too high for some bacteria
 Oxygen – availability depends on location in vivo
• Anaerobic
• Aerobic
Facultative or Obligate
• Microaerophilic
Factors controlling growth
2. Physical environment – contd.
 Temperature: 37ºC – little variation
pathogens mesophiles
 pH: Mostly ca. pH 7.0 in vivo, but can vary
• Skin: pH 5.5
• Stomach: pH 2.0 – 5.0
Factors controlling growth
3. Competition – from normal flora
 Cells occupying your space
Approx.
number
% Total
Human
1013
10%
Bacteria
1014
90%
NORMAL HUMAN FLORA
 Internal organs/tissues normally sterile
 External surfaces & accessible ‘internal’ niches
colonised by certain bacterial species – include:
• Skin
• Conjunctiva (eye surface)
• Oral cavity
• Upper respiratory tract
- Nares (nostrils) & nasopharynx
• Gastroinsteinal tract
• Urogenital tract
NORMAL HUMAN FLORA
 Numbers & composition varies depending on location
Site
numbers of bacteria
Mouth
1010
Skin
1012
Intestines
1014
• May also vary at different sites on same tissue
e.g. skin - approx 2 square meters
- moist areas more densely populated
 Complex flora : > 200 species
NORMAL HUMAN FLORA
 Skin – dominated by:
• Staphylococcus epidermidis
• Micrococcus sp.
• Coryneforms (e.g. Propionibacterium acnes)
• 20 – 30% individuals: Staphylococcus aureus
 Conjunctiva
• Numbers usually low
• Mostly S. epidermidis & certain coryneforms
• Occasionally S. aureus, some streptococci,
Neisseria sp., Haemophilus sp
NORMAL HUMAN FLORA
 Oral cavity – multiple sp., including:
• Oral streptococci (α – haemolytic)
- S. salivarius, S. mutans, S. sanguis
• Lactobacillus sp, Staphylococcus sp.
• Corynebacterium sp.
• Many anaerobes – esp. Bacteroides sp.
 Upper respiratory tract
• Nares: S. epidermidis, Corynebacteria,
S. aureus (20 – 30% individuals)
• Nasopharynx: Mostly α-haemolytic streptococci
other Streps., Neisseria sp.,
NORMAL HUMAN FLORA
 GI Tract – multiple sp., including for example:
• Escherichia coli & other Enterobactericeae
• Clostridium perfringens
• Enterococcus faecalis
• Bacteroides sp.
 Urogenital tract:
• Antherior urethra: S. epidermidis, enteric bacteria
• Vagina: various sp., including:
Lactobacillus acidophilus
Different types of symbiotic associations
Commensalism
Mutualism
Harmless
reciprocal
benefit
Parasitism
unilateral benefit
Factors controlling growth
4. Host defences – Innate and specific
Dynamic, interactions with bacteria – outcome
depends on the balance
Host defences
Bacterial virulence
H
Multiple factors
B
Multiple factors
 Pathogenicity usually a multifactorial process
 Normal flora - balance in a particular host niche,
but not necessarily at other sites
Virulence
 Quantitative – extent of ability to cause disease
Completely
avirulent
Extremely
virulent
B
H
No capacity
to survive in/on host
H
B
Overwhelm defenses
rapidly kills host
Opportunistic pathogens
Completely
avirulent
Extremely
virulent
B
H
Normal defences
No disease
H
B
Compromised defences
Disease
• Other sites are normally sterile, and the
presence of bacteria suggests an
infection:
– Blood (septicaemia)s
– Cerebrospinal fluid (meningitis)
– Deep tissues (abscesses)
• The digestive tract contains large numbers
of organisms – up to 1/3 of faeces can be
bacteria: some anaerobes are actually
oxygen-sensitive
• The vast majority of normal flora organism do
not cause disease, but coexist with the host commensals
• Much of the normal flora is actually beneficial to
the host – they can exclude pathogen, by
producing antibiotics, or other bactericidal
substances (bacteriocins)
• Removal of the normal flora by e.g. antibiotics
can make the host much more susceptible to
pathogenic organisms which would otherwise
not cause disease because the normal flora will
prevent them from colonising the host.
Homework
• Read about the Roles of Normal Flora
– Brooks chapter 11
OR
– Schaechter chapter 2