Exploring Microbes and Diseases: Streptococci, Corynebacterium, Mycobacterium, and Pathogenic Gram-Negative Bacteria

1. Microbes and diseases: what to study-1 • 1. Causative microbe: name, morphology (shape, size, Gram stain, etc.), physiology (aerobe, anaerobe, etc) and some info on classification (what's it related to?) • 2. Pathogenesis and clinical disease:  what disease does it cause (signs and symptoms) and how does it do it (capsule, toxins..)? • 3. Transmission and epidemiology: how do you get the disease?

2. Microbes and diseases: what to study-2 • 4. Diagnosis: How does the lab usually identify the causative agent? • 5. Treatment: antibiotics prescribed (or not- no cell wall, no penicillin) or other treatment (oral rehydration therapy for cholera). • 6. Prevention and control (stop the spread; condoms, kill urban rats..)

3. Significant diseases of past • Scarlet fever • Diphtheria • Leprosy • Plague • Typhus • Smallpox • Polio

4. Streptococci: G+ cocci • Genera: Streptococcus and Enterococcus • Aerotolerant anaerobes, catalase negative • Grow in chains, pairs • Strep: Lancefield groups, viridans, S. pneumoniae • Group A strep: S. pyogenes • Pharyngitis, scarlet fever, pyoderma, erysipelas, TSS, necrotizing fasciitis • Sequelae: rheumatic fever and glomerulonephritis • Group B strep: S. agalactiae • Infects newborns during birth, major neonatal dis.

5. Characteristics of Streptococcal infections http://euclid.dne.wvfibernet.net/~jvg/Bio208/resp_pix/scarlet-fever.jpg http://textbookofbacteriology.net/vvpath.jpeg

6. Virulence factors, etc. • S. pyogenes (“pus-producing”) • M protein and capsule: avoids phagocytosis • Streptokinase, streptolysins for escape & attack • Pyrogenic erythrotoxins (SPEs) • at least 3 different types • Cause scarlet fever: fever, rash; toxic shock • Beta hemolytic on blood agar

7. Corynebacterium: G+ rod • Found on humans, animals, plants • Normal microbiota, opportunists,& pathogens • C. diphtheriae: cause of disease diphtheria • Colonizes the throat, inflammation, fever, and pseudomembrane, release of toxin • Pseudomembrane can block throat • Toxin inhibits protein synthesis, kills cells locally • Toxin diffuses, kills heart and nerve cells • Antitoxin, antibiotic treatment • Vaccination (DPT); humans are only host.

8. Mycobacterium: G+ rods • Many non-pathogenic species, most disease: M. tuberculosis and M. leprae • M. avium-intracellulare: environmental source of lung disease (like TB) in AIDS patients • Mycolic acids as part of complex cell wall • Protects against desiccation • Protects against destruction by phagocytes • Requires acid-fast staining • Generally grow very slowly (chronic illnesses) • Can grow intracellularly

9. Acid Fast stain of Mycobacteria http://www.md.huji.ac.il/mirror/webpath/AIDS071.jpg

10. M. leprae • Cause of Hansen’s disease, aka leprosy • Slow growing, likes it cool; armadillos as model • Grows in peripheral nerve and skin cells • Numbness is characteristic of disease • Tuberculoid vs. lepromatous leprosy • Mild, severe, respectively, depending on cell mediated immune response. • Numbness vs tissue destruction • Spread mostly by direct contact • Treatable with antibiotics, but long term

11. Gram negative rods and cocci • Endotoxin: Lipid A, the superantigen • Part of LPS of the Gram negative outer membrane • Causes an over-stimulation of macrophages with production of various cytokines • Fever, vasodilation, inflammation, shock, and disseminated intravascular coagulation • While Gram negative pathogens can have other virulence factors (capsules, fimbriae, exotoxins), all have endotoxin and are thus dangerous. • http://www.textbookofbacteriology.net/endotoxin.html

12. Truly pathogenic enterics-3 • Yersinia: Y pestis is cause of plague, other species cause food-borne infections • Plague: 3 cycles: sylvan, urban, and human • endemic in sylvan cycle; mixing of woodland and urban rodents brings urban cycle, fleas jump from dying rats to humans. • Infection leads to large swollen lymph nodes: buboes • Bubonic plague, with high fever. • Septicemic plague: with DIC, bruising (black death) • Raises mortality from75% to near 100% • Pneumonic: coughed out and spread human to human • 100% mortality

13. The S.F. earthquake and plague http://library.thinkquest.org/03oct/00904/images/sanf.jpg http://www.cdc.gov/ncidod/dvbid/plague/plagwest.htm

14. Rickettsiae • Gram negative, very small, obligate parasites • Leaky membranes? • Most diseases spread by vectors • Rickettsiae infect endothelial cells lining blood vessels, avoid digestion in lysozome • Have LPS, generate fever • Damage to capillaries produces spots, rashes • Damage to vessels deprives organs of oxygen

15. Rickettsial diseases • R. rickettsii: Rocky mountain spotted fever • Spread by tick bite; rodents are the reservoir • Most common through southeast, mid-south • R. prowazekii: epidemic typhus • Humans primary host; vector is the louse • Disease spread in crowded, unhygienic conditions • R. typhi: murine/endemic typhus • present in rodent population, vector is the flea

16. Gallery of Rickettsial vectors Rickettsia rickettsiae: tick R. prowazekii: human louse R. typhi: flea http://www.doktordoom.com/images/Tick.jpg http://www.msmosquito.com/louse.gif http://www.shoarns.com/Flea%2040X.jpg

17. Smallpox • Variola major and minor, large DNA virus • Mortality rate 20-60% for major, also blindness • Systemic infection, produced rash • In 20th Century, WHO conquered disease • No animal reservoirs, only human • Effective vaccine • Recognizable signs and symptoms • US vaccination discontinued in 1972 • Declared gone in world in 1979

18. Smallpox visuals http://en.wikipedia.org/wiki/Smallpox

19. Polio • Picornavirus • Small RNA virus • Enterovirus: spread by fecal-oral route • Attacks GI tract • In small percentage, attacks motor neurons • Leads to paralysis of different muscles, sometimes diaphragm • Children in iron lungs to help them breath • Lack of muscle function produces skeletal defects

20. Polio continued • Epidemics peaked in mid 20th century • Salk and Sabin raced to produce vaccines • Hailed as heroes • On WHO’s list to eliminate