1. Infection and disease Lecture 3 Bacterial toxins Portals of exit Common bacterial diseases

2. (7) Bacterial toxins Toxins - Poisonous substances produced by microorganisms – Toxigenicity - The ability to produce toxins. – Toxemia refers to the presence of toxins in the blood.

3. (a) exotoxins Mostly produced by gram positive bacteria Soluble in body fluids Transported throughout blood / lymph Disease is often not due to the bacteria per se, but due to the exotoxins Most exotoxins are called AB toxins - 2 components: Active and Binding

4. Examples of exotoxins: Diptheria toxin Diphtheria; nasopharyx is affected Toxin A inhibits protein synthesis in the host cell – leads to host cell death

5. Examples of exotoxins: Cholera toxin Vibrio cholera – diarrhoea Toxin A – increased cAMP – which controls the efflux of H 2 O ions from cells Increased secretion of water and ions into the intestine Diarrhoea

6. (b) Endotoxin Gram negative bacterial cellwall have lipid A (lipopolysaccharide - LPS) – endotoxin Important for pathogenesis

7. How are endotoxins released ? Complement-mediated lysis mediated of bacteria Phagocytic digestion of bacterial cells Antibiotics usage

8. What does an endotoxin do ? ENDOTOXIN Inflammation Secretion of Cytokines Fever BBB

9. Endotoxin are pyrogens Killing of bacteria by some sterilization methods may to necessarily eliminate endotoxins Endotoxins are heat stable

10. (8) Bacterial spores Formed by some bacteria under stress / nutrient depletion Most spore forming bacteria are Gram positive bacteria Can become a vegetative cell (what we normally refer to as bacteria) under favourable conditions

11. Bacterial spores Unfavourable condition Favourable condition

12. Bacterial spores Spores are highly resistant – to heat, cold, antibiotics Spores survive for centuries under harsh conditions Spores are dormant – no reproduction High levels of calcium dipicolinate – heat resistance / DNA protection High levels of sulphur

13. Portals of exit Respiratory tract – Coughing, sneezing Gastrointestinal tract – Feces, saliva Genitourinary tract – Urine, vaginal secretions Skin Blood – Biting arthropods, needles/syringes

14. Examples of bacterial diseases

15. Tetanus Exotoxin from Clostridium tetani Neurotoxin – causes muscle spasms Starts with pain in the jaw – inability to open jaw Spreads to all the muscles throughout the body 10% untreated – die due to the toxin Vaccine preventable (DPT /TT)

16. Disease causing organismsymptomsReservoirMode of transmission Clostridium tetaniSevere spasms, rigidity of muscles, lockjaw SoilPuncture wounds contaminated by bacterial spores Source: Royal College of Surgeons of Edinburgh, Scotland Tetanus

17. Anthrax Bacillus anthracis – spore forming Spores are present in soil Common disease of grazing animals Human infection: Pulmonary anthrax – inhalation of spores Gastrointestinal anthrax – eating of infected animal meat Cutaneous anthrax – hide porter’s disease (cuts in skin) Disease is linked to exotoxin

18. Anthrax Cutaneous anthrax Anthrax – potential use in bioterrorism; Spores - inhalation

19. Plague Yersinia pestis Major outbreak in the 14 th century – 200 million deaths Many minor outbreaks Transmitted through infected rat fleas (rodents are reservoirs)

20. Plague: the disease “Black death”

21. Plague: pathogenesis Resist digestion by macrophages Spread via lymphnodes /blood / shed from lungs Human-to-human transmission – cough /aerosol Acute inflammatory response Clogs capillaries Reduced blood supply – tissue death by necrosis

22. Cholera Vibrio cholera Transmitted by contaminated food /water Severe diarrhea (exotoxin) Dehydration / can be fatal in young children if untreated

23. Cholera Oral /IV rehydration / antibiotics

24. Typhoid fever Salmonella typhi Usually transmitted by contaminated food Can affect multiple organs – including brain, lungs, heart Small proportion (<5%) – asymptomatic carriers bacteria replicates Able to spread disease

25. Typhoid Mary Asymptomatic carrier – cook; several families were infected, changed jobs. Quarantined for 3 decades

26. TB Mycobacterium tuberculosis Inhalation (long-term contact) ~90% - latent infection (No replication) ~10%- progression to pulmonary TB (immune system not able to control replication) Fever > 3 weeks, fatigue, cough, night sweat..

27. TB Extrapulmonary TB – brain, bone, joint Slow grower (~18 hours to double) Requires special antibiotics Requires long-term treatment

28. Food poisoning Symptoms due to bacteria take > 2 days to manifest Pre-formed exotoxins

29. Food poisoning Vomitting, abdominal pain Eg. Staphylococcus aureus Eg. Salmonella species Antibiotics may not prevent disease

30. Can normal flora cause disease ? Yes ! Eg. E.coli (normally in the intestine) – can cause urinary tract infection