Medical MicrobiologySBM 2044

Assoc Prof Dr Othman Abd SamahTel : 09-5716744

Email : oas@iiu.edu.my

Sr. Intan Azura ShahdanTel : 09-5716400 ext 2816

Email : intan_azura@iiu.edu.my

SBM 2044 LECTURE 1

INTRODUCTION TO MODULE

• Methods of assessment

• Module Aims & Objectives

• Course structure, Reading, etc.

• Introduction – Recall some foundations from Principles of Microbiology SBM 2053

Value: 4 credit hours

SBM 2044: Aims

To foster knowledge and understanding of certainmicrobial 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

• Introduction to bacterial pathogenesis

• Factors influencing bacterial-host interactions

Lecture 2:

Lecture 3:

• Weapons delivery and deployment

Today1. 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?

3%6%

8%

20% 63%

NutritionalInjury

Perinatal

Various Non-communicable

INFECTIOUSDISEASE

Deaths in children (0 – 4 years) in 1998

Data from WHO 1999

Vineeth, 7 months old and identified as HIV-positive, 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 mother-to-child transmission.

NutritionalMaternal

Various non-communicable Injuries

Perinatal

INFECTIOUSDISEASE

48%19%

18%

10%3% 2%

Premature deaths (0 – 44 years) in 1998

Data from WHO 1999

Deaths 1945 – 1993 (in millions)

War

AIDS + Malaria + TB

Spending 1995(in billions $)

Military

AIDS + Malaria + TB

Human priorities ?

23

150

15

864

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 postulates1. 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 growthFactors 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 growthFactors controlling growth

2. Physical environment

Water activity (aw) - not limiting in vivo

Osmotic pressure (π) - moderate/high

Oxygen – availability depends on location in vivo

• Anaerobic Facultative or Obligate• Aerobic

• Microaerophilic

• Too high for some bacteria

Factors controlling growthFactors controlling growth

2. Physical environment – contd.

Temperature: 37ºC – little variation

pH: Mostly ca. pH 7.0 in vivo, but can vary

pathogens mesophiles

• Skin: pH 5.5

• Stomach: pH 2.0 – 5.0

Factors controlling growthFactors controlling growth

3. Competition – from normal flora

Approx. number % Total

Human

Bacteria 1014

1013

Cells occupying your space

10%

90%

NORMAL HUMAN FLORANORMAL HUMAN FLORA

Internal organs/tissues normally sterile

External surfaces & accessible ‘internal’ niches colonised by certain bacterial species – include:

• Skin

• Oral cavity

• Upper respiratory tract

• Gastroinsteinal tract

• Urogenital tract

- Nares (nostrils) & nasopharynx

• Conjunctiva (eye surface)

NORMAL HUMAN FLORANORMAL HUMAN FLORA

Site numbers of bacteria

Skin 1012

Mouth 1010

Intestines 1014

Numbers & composition varies depending on location

• 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 FLORANORMAL HUMAN FLORA

Skin – dominated by:• Staphylococcus epidermidis

• 20 – 30% individuals: Staphylococcus aureus

Conjunctiva

• Numbers usually low

• Mostly S. epidermidis & certain coryneforms

• Micrococcus sp. • Coryneforms (e.g. Propionibacterium acnes)

• Occasionally S. aureus, some streptococci, Neisseria sp., Haemophilus sp

NORMAL HUMAN FLORANORMAL 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 streptococciother Streps., Neisseria sp.,

NORMAL HUMAN FLORANORMAL 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

reciprocalbenefit

unilateral benefit

Commensalism

Harmless

Parasitism

Mutualism

Different types of symbiotic associations

Factors controlling growthFactors controlling growth

4. Host defences – Innate and specific

Dynamic, interactions with bacteria – outcome depends on the balance

H B

Host defences

Multiple factors

Bacterial virulence

Multiple factors

Normal flora - balance in a particular host niche, but not necessarily at other sites

Pathogenicity usually a multifactorial process

Overwhelm defensesrapidly kills host

No capacityto survive in/on host

Completelyavirulent

Extremelyvirulent

VirulenceVirulence

H

B

B

H

Quantitative – extent of ability to cause disease

Compromised defencesDisease

Normal defencesNo disease

Completelyavirulent

Extremelyvirulent

H

B

B

H

Opportunistic pathogens

• 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