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Medical Microbiology SBM 2044

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Medical Microbiology SBM 2044 Assoc Prof Dr Othman Abd Samah Tel : 09-5716744 Email : oas_at_iiu.edu.my Sr. Intan Azura Shahdan Tel : 09-5716400 ext 2816 – PowerPoint PPT presentation

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Title: Medical Microbiology SBM 2044


1
Medical MicrobiologySBM 2044
  • Assoc Prof Dr Othman Abd Samah
  • Tel 09-5716744
  • Email oas_at_iiu.edu.my
  • Sr. Intan Azura Shahdan
  • Tel 09-5716400 ext 2816
  • Email intan_azura_at_iiu.edu.my

2
SBM 2044 LECTURE 1 INTRODUCTION TO MODULE
Value 4 credit hours
  • Methods of assessment
  • Module Aims Objectives
  • Course structure, Reading, etc.
  • Introduction Recall some foundations from
    Principles of Microbiology SBM 2053

3
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

4
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

5
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

6
Today
  1. How do we recognise pathogens?
  2. Only a tiny proportion of all known microbes
    cause disease
  3. How do we identify a particular microbe as the
    cause of a particular disease?
  4. Which microbes cause disease?
  5. How do they do it?
  6. How do we stop them?
  7. How do we identify a particular microbe as the
    cause of a patients illness?

7
Deaths in children (0 4 years) in 1998
Data from WHO 1999
8
(No Transcript)
9
Premature deaths (0 44 years) in 1998
Nutritional
Maternal
Perinatal
2
3
10
INFECTIOUS DISEASE
18
48
19
Various non- communicable
Injuries
Data from WHO 1999
10
Human priorities ?
Spending 1995 (in billions )
Deaths 1945 1993 (in millions)
AIDS Malaria TB
War
15
23
150
864
AIDS Malaria TB
Military
11
How do we identify a particular microbe as the
cause of a particular disease?
  • The Koch Henle postulates
  • Isolate the organism from every case
  • Propagate in pure culture in vitro
  • Reproduce disease by injecting the organism into
    a suitable recipient
  • Re-isolate the organism
  • OK for major acute diseases like plaque,
    smallpox, typhoid..

12
  • 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.

13
Factors controlling growth
1. Nutrient availability
  • Essential elements
  • Major C, O, H, N, S, P, K, Mg, Ca, Fe, Na, Cl
  • Minor Zn, Mn, Mo, Se, Co, Cu, Ni, W
  • 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

14
Factors controlling growth
2. Physical environment
  • Water activity (aw) - not limiting in vivo
  • Osmotic pressure (p) - moderate/high
  • Too high for some bacteria
  • Oxygen availability depends on location in
    vivo
  • Anaerobic
  • Aerobic
  • Microaerophilic

15
Factors controlling growth
2. Physical environment contd.
  • Temperature 37ºC little variation
  • pH Mostly ca. pH 7.0 in vivo, but can vary
  • Skin pH 5.5
  • Stomach pH 2.0 5.0

16
Factors controlling growth
3. Competition from normal flora
  • Cells occupying your space

Approx. number
Total
10
1013
Human
90
1014
Bacteria
17
  • Humans are born sterile - adults can have up to
    1014 bacteria
  • These are found in
  • Skin digestive tract urinary tract
  • Respiratory tract genital system
  • Other sites are normally sterile, and the
    presence of bacteria suggests an infection
  • Blood (septicaemia)
  • Cerebrospinal fluid (meningitis)
  • Deep tissues (abscesses)

18
  • The normal flora varies markedly at different
    sites of the body, and is made of resident
    organisms which are stable and a transient flora
    of organisms from the environment.
  • Most of us carry an overcoat of staphylococci
    on the skin.
  • The digestive tract contains large numbers of
    organisms up to 1/3 of faeces can be bacteria
    some anaerobes are actually oxygen-sensitive

19
  • The upper respiratory passages contain a mixture
    of Gram-positive and negative organisms.
  • 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
    subastances (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.

20
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

21
NORMAL HUMAN FLORA
  • Numbers composition varies depending on
    location

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 gt 200 species

22
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

23
NORMAL HUMAN FLORA
  • Oral cavity multiple sp., including
  • Oral streptococci (a 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 a-haemolytic streptococci
  • other Streps., Neisseria sp.,

24
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

25
Different types of symbiotic associations
Mutualism
Commensalism
reciprocal benefit
Harmless
Parasitism
unilateral benefit
26
Factors controlling growth
4. Host defences Innate and specific
  • Dynamic, interactions with bacteria outcome
  • depends on the balance

Host defences
Bacterial virulence
Multiple factors
Multiple factors
  • Pathogenicity usually a multifactorial process
  • Normal flora - balance in a particular host
    niche,
  • but not necessarily at other sites

27
Virulence
  • Quantitative extent of ability to cause
    disease

Completely avirulent
Extremely virulent
Overwhelm defenses rapidly kills host
No capacity to survive in/on host
28
Opportunistic pathogens
Completely avirulent
Extremely virulent
B
H
H
B
Normal defences No disease
Compromised defences Disease
29
Pathogens and Infections
  • Pathogens are closely related to commensals, but
    differ in that they can cause DAMAGE.
  • A pathogen is therefore an organism which can
    damage the host.
  • The capacity of an organism to cause disease is
    referred to as PATHOGENICITY, or sometimes
    VIRULENCE. Organisms which are very capable of
    causing disease are called highly virulent.

30
COURSE STRUCTURE
  • Introduction
  • Common themes - Cell surfaces (reminder)
  • - Weapons deployment
  • - Experimental approaches

31
Overview of Bacterial Pathogenesis
Encounter
Sources Transmission
Entry
First-line
Adhesion to a surface and/or Invasion of tissues
non-specific host defences
Inflammation
Multiply spread
specific host defences
Cell tissue damage
Exit
32
Overview of interactions with host surfaces
Transient step, leading to
Transient step, leading to
Colonization of surface
Complex biofilms
Invasion
33
Mechanisms of cell tissue damage
Hypersensitivity Autoimmunity
Inflammation
INDIRECT DAMAGE
BACTERIAL PATHOGENS
Growth in host cells
Harmful metabolites
DIRECT DAMAGE
S. mutans lactic acid tooth decay
Degradative enzymes
TOXINS
34
Bacterial interactions with host
Key bacterial factors
  • Cell-surface components
  • Secreted products
  • Regulation of their expression

35
Bacterial cell surface
Gram-positive
Gram-negative
Cytoplasmic membrane
Outer membrane
Peptidoglycan
36
Gram-negative bacteria
Gram-positive bacteria
OM
IM
Peptidoglycan
ca. 40 layers
ca. 1 or 2 layers
37
Weapons Delivery
  • Bacteria must
  • distinguish proteins destined for secretion from
  • cytoplasmic proteins
  • translocate secreted proteins across hydrophobic
  • membranes

38
General Secretion Pathway (GSP)
Most secreted bacterial proteins expressed as
larger precursors with an N-terminal secretion
signal-peptide
recognized by
membrane-associated secretory apparatus (Sec) -
includes a signal peptidase that removes
signal peptide during translocation thro membrane
Sec complex, includes signal-peptidase
Signal-sequence
39
SECRETION SIGNAL PEPTIDES
N-terminus of secreted protein
1 - 3 charged
about 15 -20 mainly hydrophobic residues
A x B
N
A x B Leu Gly
Ala Ala Ile any Gly Val Ser
Ser
Consensus cleavage site about 6
residues downstream from hydrophobic domain
40
General Secretion Pathway (GSP)
SecB chaperon maintains protein in
secretion-competent state by
preventing premature folding in cytoplasm
41
GSP Sec-dependant secretion
Gram-positive bacteria
Gram-negative bacteria
Sufficient to get protein out of the cell
Proteins reach periplasm, but OM is additional
barrier - need other mechansims to get protein
thro OM.
OM
IM
sec
sec
Signal-peptide
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