Helicobacter pylori (Chapter 33, Murray) Gram negative Curved or spiral bacteria

1. Helicobacter pylori (Chapter 33, Murray) Gram negative Curved or spiral bacteria Microaerophilic (reduced oxygen) Gastric and duodenal ulcers “slow” pathogen (decades) widespread among humans 50% of world population infected 5-10% have clinical symptoms of disease Bacteria colonize gastric mucosa (mucous layer) Bacteria raise local pH (by producing urease) Spread likely person to person (fecal-oral / oral-oral) (found in dental plaque)

2. Diagnosis Urease test of endoscopic sample Histological sample/culturing of bacteria Treatment Antibiotics (amoxicillin, clarithromycin, metronidazole) Acid reduction therapy (H2 blockers/proton pump inhibitors)

3. Pseudomonas aeruginosa (Chapter 34, Murray) Gram-negative rods aerobic motile - polar flagella (vs. E. coli) P. aeruginosa live in soil and water (ubiquitous) get energy from oxidation of sugars (do not ferment) if no oxygen as final electron acceptor, can use NO3- O2 H2Ovs. NO3- NO2- NON2O N2 Pseudomonads have minimal nutrient requirements can grow on only acetate (C source) and ammonia (N source) indophenol oxidase positive use Entner-Doudoroff pathway and pentose phosphate pathway instead of glycolysis

4. Opportunistic pathogen - cause disease when host defenses are impaired Healthy persons - neutrophils destroy bacteria Pseudomonas bacteria are extracellular pathogens invasion of host cells not important in most tissue (except eye) Virulence factors Adhesins pili non pilus adhesins 2 are proteins, 1 is LPS (binds a chloride channel) LPS also plays a role in eliciting inflammation/fever Protein secretion system (type III) injects toxic proteins into host cell cytoplasm

5. ExoS and ExoT (exoenzymes) ADP ribosylation of G proteins (interfers with signalling) neutrophils ExoU - toxic for macrophages Exotoxin A (an A-B toxin) ADP ribosylation of EF-2 local inflammation and tissue destruction Elastolytic activity (destruction of elastin, 30% of lung protein) Elastase (protease) - 2 protein enzyme Alkaline protease Phospholipase

6. Alginate production polysaccharide capsule factor in biofilm formation in lungs of cystic fibrosis patients Phase variation turns alginate production on/off LPS phase variation - changes LPS structure Antibiotic resistance porin protein mutants (drugs cannot get in) b-lactamases

7. Diseases respiratory and urinary tract infections wound infections Burns Nosocomial infections cystic fibrosis - biofilm (mucoid strains) alginate polymers inhibits diffusion of antibiotics Treatment aminoglycosides quinolones (ciprofloxacin - DNA gyrase inhibitor) usually treated with 2 antibiotics because of drug resistance

8. Haemophilus influenzae(Chapter 35, Murray) Gram-negative rods aerobic 50% of childhood bacterial meningitis cases 30% of childhood middle ear infections (otitis media) Uncontrolled growth triggers inflammatory response local tissue damage, could lead to septic shock Virulence factors capsule IgGA1 protease Treatment Vaccine (Hib) (against capsule polysaccharide) 2nd generation cephalosporins (resistant to b-lactamase) ceftriaxone, ceftaxime

9. Bordetella pertussis (Chapter 36, Murray) gram-negative coccobacilli (rods that resemble cocci) strict aerobe exclusively human pathogen agent of whooping cough in infants milder symptoms in adults Transmission airborne (droplets) and direct contact Bacteria attach to the surface of ciliated epithelial cells bacteria remain on cell surface filamentous hemagglutinin (Fha) pertactin and pili damage to epithilial cells occurs

10. Bacteria produce pertussis toxin ADP ribosyl transferase - attaches ADP ribose to a G protein that regulates adenylate cyclase result is increased cAMP production by host cell cellular ion flow disrupted (increase mucous) also inhibits neutrophils pertussis toxin is an A-B toxin B subunit of pertussis toxin is composed of 5 proteins Invasive ACase Adenylate cyclase (in form of an A-B toxin)

11. Dermonecrotic toxin (pertussis heat-labile toxin) skin lesions (in animal studies) vasoconstriction Tracheal cytotoxin peptidoglycan fragment released into extracellular fluid kills ciliated epithelial cells LPS 2 types activate alternative complement pathway stimulate cytokines

12. Diagnosis culture, but not always detected early stages indistinguishable from common cold Treatment erythromycin, ampicillin treatment does not lessen duration of symptoms but lessens infectivity (spread) vaccine DTP (DTaP) Diphtheria toxoid Tetanus toxoid Pertussis toxoid + Fha adhesin

13. Legionella (Chapter 38, Murray) • Gram negative • Aerobic • Rods (bacilli) • Legionella pneumophila • Opportunistic infections (water-borne) • Acquired by inhalation (of water aerosol) • Bacteria are ingested by alveolar macrophages • But they grow inside of macrophages • Bacteria prevent fusion of phagosome with lysosome • (result is specialized endosomes) • macrophage ruptures/dies as bacteria grow inside • cell-mediate immune response limits bacterial growth in macrophages (-interferon)(decreased iron available in macroph.)

14. most people do not get infection if exposed to Legionella risk factors: smoking, pulmonary disease, old age Diagnosis Treatment Antibiotic treatment (cell-penetrating) Erythromycin Tetracycline

15. Bartonella(Chapter 39, Murray) Gram-negative bacilli Bartonella henselae Agent of cat scratch disease (scratch or bite; maybe fleas or lice) 20,000 cases annually in U.S. small skin papule at site of inoculation bacterial spread to regional lymph nodes multiply in lymph nodes host immune response generated/usually limits infection Bacteria secrete substances that promote blood vessel formation bacillary angiomatosis – tumorlike proliferation of blood vessels in skin and visceral organs

16. clinical manifestations • swollen lymph nodes, malaise, and fever • usually self-limited disease • AIDS patients - host reponse insufficient • Systemic infection with large numbers of bacteria • Get sepsis and localized infections (skin, liver, etc.)

17. Bartonella quintana • Trench fever in World War I (febrile bacteremia) • vector = human body louse • Also causes bacillary angiomatosis • Bartonella bacilliformis • South America; bacteria acquired by bite of sandfly • Oroya fever • bacteria enter RBC's and multiply • RBC's destroyed by immune reponse (phagocytosis) • Result is severe anemia • Bacillary angiomatosis

18. Diagnosis • Clinical history of cat scratch, signs and symptoms, and PCR • Culture of blood or skin lesions • Immunoassays • Treatment • Cat scratch disease – no effective treatment, but disease not • serious • Angiomatosis treatment – erythromycin, doxycyline, • azithromycin

19. Clostridia(Chapter 40, Murray) Gram positive Anaerobic Rods (bacilli) Spore-forming 30 species infect humans (at least 14 produce protein toxins associated with disease) 50+ other species in soil and animal wastes Clostridium difficile Diarrheal disease Pseudomembranous colitis – ulcerating disease of the large intestine Pseudomembrane – plaques of fibrin + cellular components Overlays ulcerations of mucosa Infection is linked to antibiotic treatment low numbers of C. difficile present in large intestine spores resistant to antibiotics (competitors killed)

20. Bacteria do not invade tissue • Cytotoxins cause damage to epithelium • Cytotoxin-a type of toxin that causes direct damage to cells • Toxin A and toxin B • Diagnosis • Presence of toxins in stool samples • Treatment • Metronidazole (antibiotic)

21. Clostridium botulinum Agent of botulism – contaminated canned foods (esp. home-made) Spores germinate in anaerobic environment and produce toxins Bacteria do not invade tissue Neurotoxins 8 different toxins produced by C. botulinum A and B toxins (sometimes E) account for most of disease cases Toxins alone can cause symptoms of disease Toxins are heat-labile 1ug can kill a large family toxin prevents release of neurotransmitter acetylcholine symptoms start 12-36 hr post infection flaccid paralysis of muscle face first location (double/blurred vision) throat (difficulty swallowing) eventually respiratory failure

22. Diagnosis Treatment treat with antitoxin (anti-A, -B, + -E = trivalent antitoxin) illness lasts ~ 1week individual muscles can be paralyzed for months/permanently 25% mortality with rapid care infant botulism age 3-20 weeks colonize large intestine paralysis but slow onset/ favorable outcome wound botulism wound contaminated with spores severe disease (like food-borne disease)

23. Clostridium tetani Agent of tetanus Part of normal gut flora and also in soil Spores get into deep wound (anaerobic environment) Germinate and produce toxins But no tissue invasion Tetanospasmin toxin Major toxin – account for all symptoms 2 proteins (AB toxin) toxin attaches to peripheral nerves near wound and transmitted to cranial nerve nuclei toxin prevents release of several neurotransmitters, including GABA (-aminobutyric acid) and inhibitory input (reflex spasms)

24. causes spastic paralysis (vs. flaccid) begins with lockjaw progresses to neck/shoulders generalized spasm death due to respiratory failure (paralysis of chest muscles) Diagnosis Treatment antitoxin – need to use very early after infection antibiotic treatment – kill bacteria that may continue producing toxin penicillin G cleaning of wounds (make aerobic) immunization is best protection T of DPT or DTaP Tetanus booster every 10 years

25. Clostridium perfringens • Tissue invasion • Gas gangrene (necrotizing of muscle tissue) • Cellulitis • Spores get into deep wound (anaerobic) • Germinate and produce toxins • 12 different types of toxins • lecithinase (cytotoxin)- damages cell membranes/kill cells • bacteria invade tissue by destroying cells • gas in produced by bacteria as they grow • Diagnosis • Treatment • removal of involved muscle – tissue resection/amputation • antitoxin not effective • antibiotic treatment (penicillin); clean wound (make aerobic) • oxygen treatment (hyperbaric oxygen)

26. Bacteroides (Chapter 42, Murray) gram-negative rods (bacilli) strict anaerobes members of the normal gut and oral flora Bacteroides fragilis the most oxygen-resistantBacteroides superoxide dismutase - detoxifies oxygen radicals catalase - breaks down hydrogen peroxide Virulence factors 1. Polysaccharide capsule 2. Neuraminidase - cleaves sialic acid from host carbohydrates bacteria then use sialic acid as energy source 3. Lipases - cleave host lipids 4. Proteases- cleave host proteins

27. Disease caused when bacteria are introduced into deep tissues peritonitis - rupture of infected appendix/diverticulum pulmonary abscess - aspiration of oropharyngeal bacteria Bacteroides fragilis is one component in these diseases polymicrobial diseases biphasic - start with acute inflammation progress to formation of localized abscesses bacterial composition changes as disease progresses 100’s of different species in inoculum few species in abscess due to response of the host and features of individual bacterial species

28. Abscess = local collection of pus Development involves both bacteria and host factors Early: acute inflammatory response (neutrophils) Some neutrophils lysed by bacteria (neutrophil contents damaging) Host surrounds area with thick-walled fibrin capsule Blood supply is cut off Center of abscess necrotic Dead neutrophils, dead and live bacteria Edema fluid Problems if abscess located in a vital area of the body.

29. Course of disease perforation of intestine/spillage of intestinal fluid neutrophils mobilized surviving bacteria resistant to phagocytosis B. fragilis has a capsule oxygen-sensitive bacteria are killed peritoneal cavity well-oxygenated facultative anaerobes grow first (E. coli) some strict anaerobes survive site becomes anaerobic surviving strict anaerobes become predominant

30. Treatment drainage antibiotics (based on identification of bacteria) target is seldom a single species