Current Diseases

1. Current Diseases • Staphylococcus • Clostridia • Food-borne bacteria • Malaria • Influenza • Common cold • HIV • HPV

2. Staphylococcus: G+ coccus • S. aureus and S. epidermidis (and 21 others). • S. aureus much worse, S. epi an opportunist. • Sturdy, salt tolerant, fac anaerobes; clusters • S. epidermidis common on skin, S. aureus less. • Diseases of S. aureus • Invasive: skin diseases (rashes, abscesses) • systemic diseases (bacteremia, organ and bone infections) • Toxin: toxic shock syndrome, scalded skin syndrome, food poisoning • Diseases spread by fomites and direct contact.

3. Characteristics of S. aureus infections tray.dermatology.uiowa.edu/ DIB/SSSS-002.htmwww.omv.lu.se/.../ rorelse/popup/01d1x.htm

4. S. aureus virulence factors & Rx • Capsules, hyaluronidase, staphylokinase, beta-lactamases (destroy penicillins), leukocidins • Toxins: various, including TSS toxin, exfoliatin, and enterotoxins (heat stable) • 95% resistant to penicillin, but now many resistant to methicillin, oxacillin. Treatment usually clindamycin (oral) or vancomycin (IV). • S.aureus carried by 30-40% • Well adapted to life with humans • http://www.textbookofbacteriology.net/staph.html

5. Clostridium: G+ rods • Strict anaerobes! Endospore formers. Toxigenic • Common in soil, sewage animal GI tracts • Produce neurotoxins, enterotoxins, histolytic toxins • Four important species: C. perfringens, C. botulinum, C. tetani, and C. difficile. • C. perfringens • Food poisoning: cramps and diarrhea • From injury: myonecrosis to gas gangrene • Fermentation in tissues, killing of tissues and spread of cells into anaerobic areas. • Oxygen treatment, debridement, amputation

6. More clostridia • C. difficile: normal GI microbiota • Cause of pseudomembranous colitis, resulting from overgrowth following broad spectrum antibiotics • Damage to GI wall can lead to serious illness • Nosocomial infection, easily transmitted • C.botulinum: cause of botulism • Usually acquired by ingestion: intoxication • Food borne, infant (no honey), wound • Produces neurotoxin, inhibits acetylcholine release • Flaccid paralysis; Botox: deadly poison / beauty • Mouse bioassay; administer antitoxin

7. Opposing muscle groups When biceps contracts, triceps relaxes. When triceps contracts, biceps relaxes. Excitatory neurons send signal to contract, inhibitory neurons send signal to NOT contract. http://upload.wikimedia.org/wikipedia/sv/thumb/d/dd/185px-Muscles_biceps_triceps.jpg

8. Function of nerves http://upload.wikimedia.org/wikipedia/fr/thumb/e/e4/200px-Synapse.png http://www.people.virginia.edu/~dp5m/phys_304/figures/motor_unit.jpg

9. More clostridia-2 • C. tetani: cause of tetanus • Growth in anaerobic wounds, makes tetanus toxin • Toxin prevents action of inhibitory neurons • Opposing muscle pairs both contract • Spastic paralysis, leading to death. • Recommendation is booster shot every 10 years • Toxoid vaccine, with diphtheria toxoid • No natural immunity: you would die first.

10. Gram negative rods • Enteric bacteria • Gram negative, rod shaped, facultative anaerobes, non-spore forming, oxidase negative; Proteobacteria • Possess endotoxin • Medically significant but taxonomically similar • Distinguished with biochemical tests and serological tests. • Serological tests: using specific antibodies (as found in serum) to distinguish small differences in surface molecules of bacteria.

11. http://www.ratsteachmicro.com/Assets/Enterobacteriaceae/Enterobact_diagram2.gifhttp://www.ratsteachmicro.com/Assets/Enterobacteriaceae/Enterobact_diagram2.gif

12. E. coli: friend or foe? • E. coli: cause of 90% of urinary tract infections • Most strains common to GI tract, not harmful there. • Strains have fimbriae needed for attachment • Proanthocyanidins in cranberry juice interfere • E. coli: common cause of diarrhea • Many strains possess genes (some on plasmids) that code for additional virulence factors like exotoxins which cause disease • E. coli O157:H7: possesses shiga toxin; strain causes hemolytic uremia syndrome, damages kidneys. • E coli strains classified as EHEC, EIEC, EPEC, etc. • Enterohemorrhagic, enteroinvasive, etc.

13. Truly pathogenic enterics • Salmonella: species so closely related that they are really all S. enterica. But medically, species epithets still used: S. typhi and others. Divided serologically. • Present in eggs, poultry, on animals such as reptiles • Large dose results in food poisoning; diarrhea, fever, etc. • Cells phagocytized by intestinal lining cells, kill cells causing symptoms, may pass through into blood. • S. typhi: typhoid fever. Spread through body • Gall bladder as reservoir; Typhoid Mary • http://www.pbs.org/wgbh/nova/typhoid/ • Importance of clean water and sewage treatment.

14. Truly pathogenic enterics-2 • Shigella: especially S. sonnei (most common) and S. dysenteriae (most serious); cause shigellosis. • Food, flies, fingers, feces, fomites: very small infectious dose, personal hygiene important in prevention. • Infection of intestinal lining damaged, cells pass directly from cell to cell; cramps, diarrhea, bloody stools. • S. dysenteriae produces shiga toxin which inhibits protein synthesis, increases damage. • Most serious problem with diarrheal diseases in general is dehydration.

15. Gram negative curved rods • Vibrio: comma shaped • Like enteric but oxidase positive; polar flagella • Halotolerant to halophilic, grow in estuarine and marine environments • V. cholerae: cause of cholera • Toxin-mediated severe diarrhea • Salt, fluid leave intestinal cells, patient dies of dehydration. • Oral rehydration therapy (ORT): water, salts, and glucose, now saving lives. • Causes pandemics that spread around the world • Lack of adequate sewage treatment

16. Campylobacter • Campylobacter jejuni: number one cause of bacterial gastroenteritis; zoonotic • More common than Salmonella and Shigella combined for food borne disease. • Most retail chickens are contaminated; improperly cooked chicken and contaminated milk typical vehicles. • Low infectious dose http://www.shef.ac.uk/staff/newsletter/vol23no10/images/campylobacter.gif

17. Helicobacter pylori • Cause of ulcers and gastritis • 2005 Nobel Prize for Medicine or physiology to Barry Marshall and J Robin Warren • Unusual because it can live in stomach • Produces urease enzyme • Released ammonia neutralizes stomach acid, irritates stomach lining. • Basis for radioactive urease test. • Correlated with stomach cancer. http://s99.middlebury.edu/BI330A/STUDENTS/KASSIS/images/pylori1b.jpg

18. Rogue’s gallery-4 • Sporozoans • Plasmodium: the cause of malaria, several species • Involves mosquito, liver, red blood cells in a complex life cycle. • Features a synchronous bursting of RBCs with fever, delerium, followed by rest and recovery, then cycle • Number one cause of global mortality and morbidity Yearly: 300-500 million new cases; 1 million deaths. Intracellular plasmodia www.sirinet.net/ ~jgjohnso/plasmodium.html

19. Life cycle of Plasmodium www.sirinet.net/ ~jgjohnso/plasmodium.html

20. In the poorest parts of the world, where effective window screens are lacking, insecticide-treated bed nets are arguably the most cost-effective way to prevent malaria transmission. One bed net costs just $10 to buy and deliver to individuals in need. One bed net can safely last a family for about four years, thanks to a long-lasting insecticide woven into the net fabric.

21. Orthomyxovirus • Influenza: a serious respiratory disease • Virus has a segmented genome • 8 different RNA molecules • Spikes: Hemagglutinin and Neuraminidase • Major antigens recognized by immune system • Antigenic drift and shift • Drift: small mutations, making host susceptible • Requires new vaccine each year • Shift: major mixing of RNAs, whole new virus.

22. View of flu http://www.astrosurf.org/lombry/Bio/virus-influenza.jpg http://www-micro.msb.le.ac.uk/3035/3035pics/flusection.jpg

23. Nature of influenza • Attack on respiratory tract • Kills ciliated epithelial cells, allows bacterial infections. • Release of interferon from cells causes symptoms • H antigen (hemagglutinin) for attachment • That it agglutinates RBCs is an artifact • N antigen: neuraminidase • Cuts of the sugar on the glycoprotein receptor • Allows new virions to escape from cell without getting stuck

24. Role of H and N spikes and host cell polysaccharide

25. influenza • Changes in H and N (antigenic shift) • Mixing of viruses that infect birds, pigs, produce new strains able to jump to humans. • New antigenic type leaves population unprotected • Numerous epidemics throughout history • Flu of 1918-1919 killed 20 million • Asia watched very carefully: bird flu? • Flu vaccines made from deactivated viruses • Slow process (vaccine made in eggs), so every year correct strains are “guessed”. • Cell culture would be quicker but more $

26. The Common cold • Rhinoviruses have many serotypes • Variants, caused by easy mutation of RNA • Immune system can’t recognize all differences, but some protection with age. • Multiplies in narrow temperature range, nose/sinus cooler than body temperature • Other cold viruses • Coronavirus (best known cousin causes SARS) • Adenovirus (DNA virus), some serotypes cause GI infections

27. HIV: Human Immunodeficiency Virus • Host range • Main types of cells infected: T helper cells and dendritic cells (including macrophages, microglia) • Have CD4 and CCR5 glycoproteins on surface • Infection process • RNA is copied into cDNA by reverse transcriptase • cDNA inserts into host chromosome • New RNA made • Protein precursor made, then processed; assembly occurs • Virions bud through cell membrane

28. Disease process • Chronic infection • T cells continually made, continually destroyed • Eventually, host loses • AIDS diagnosis: • Acquired Immuno Deficiency Syndrome • CD4 cell count below 200/µl; • opportunistic infections • Examples of opportunistic “infections” • Pneumocystis carinii pneumonia (PCP pneumonia) • Kaposi’s sarcoma; Tuberculosis; several others

29. Prevention and Treatment • Prevention is easy • Practice monogamous sex, avoid shared needles • HIV cannot be spread by casual contact, skeeters • Drug treatment • Nucleoside analogs such as AZT • Protease inhibitors prevent processing of viral proteins Nifty animation at: http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__hiv_replication.html

30. HPV • Papilloma virus • Cause of warts, in this case, genital warts • Virus tricks cell into preparing for cell division • Protein E7 binds to pRB • Leads to greater susceptibility to cancer, particularly cervical cancer (and penile and anal cancer) • Especially those viral strains that aren’t good at causing actual warts • CDC researchers: estimated 20 million people in the US have human papillomavirus type16 (HPV-16) infections (50% of all cervical cancers)

31. Gardasil • New vaccine • Protects against HPV types 16, 18, 6, and 11 • These biotypes account for 70% of cases of cervical cancer and 90% of cases of genital warts. • Vaccine: a recombinant vaccine w/ capsid proteins • Estimate: 3,700 to die of cervical cancer in 2006 • Controversy: should it be mandatory? • Religious right, big Pharmaceutical lobby, etc.