1. Medical Microbiology SBM 2044 Assoc Prof Dr Othman Abd Samah Tel : 09-5716744 Email : oas@iiu.edu.myoas@iiu.edu.my Sr. Intan Azura Shahdan Tel : 09-5716400 ext 2816 Email : intan_azura@iiu.edu.myintan_azura@iiu.edu.my

2. 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

3. 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

4. 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

5. 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

6. 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?

7. Nutritional Injury Perinatal Various Non- communicable INFECTIOUS DISEASE Deaths in children (0 – 4 years) in 1998 Data from WHO 1999

8. 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.

10. Nutritional Maternal Various non- communicable Injuries Perinatal INFECTIOUS DISEASE 48% 19% 18% 10% 3% 2% Premature deaths (0 – 44 years) in 1998 Data from WHO 1999

11. Deaths 1945 – 1993 (in millions) War AIDS + Malaria + TB Spending 1995 (in billions $) Military AIDS + Malaria + TB Human priorities ? 23 150 15 864

12. 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

13. 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..

14. 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.

15. 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 -18 M  Pathogens All heterotrophic (need organic C source) Many fastidious

16. Factors 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

17. Factors 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

18. Factors controlling growth 3. Competition – from normal flora Approx. number % Total Human Bacteria 10 14 10 13  Cells occupying your space 10% 90%

19. NORMAL 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)

20. NORMAL HUMAN FLORA Sitenumbers of bacteria Skin10 12 Mouth10 10 Intestines10 14  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

21. NORMAL 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

22. 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.,

23. 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

24. reciprocal benefit unilateral benefit Commensalism Harmless Parasitism Mutualism Different types of symbiotic associations

25. Factors 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

26. Overwhelm defenses rapidly kills host No capacity to survive in/on host Completely avirulent Extremely virulentVirulence H B B H  Quantitative – extent of ability to cause disease

27. Compromised defences Disease Normal defences No disease Completely avirulent Extremely virulent H B B H Opportunistic pathogens

28. 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

29. 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.

30. Homework Read about the Roles of Normal Flora – Brooks chapter 11 OR – Schaechter chapter 2