Bacteria

SALMONELLA



Structure/ID:

 Gram (-) rods, encapsulated

 Motile (like a salmon) with flagella

 (-) Lactose fermentation (colorless on MacConkey)

 (+) H2S

 Ags: O (cell wall), Vi (capsule around O (= K Ag)), H (flagella) – variable to avoid Abs



Virulence factors:

 Vi (virulence) Ag in capsule – inhibits opsonization

 LPS (endotoxin released on lysis)

 Type III secretion organelle

 Can survive in MΦ’s (resistant to lysosomal enzymes)

 S. enteritidis – cholera-like toxin



Pathogenesis:

 Fecal-oral transmission from animals (via chicken, raw eggs, etc.)

 S. typhi:

1. Invades cells of distal ileum & colon by inducing ruffling/phagocytosis (type III secretion)

2. Crosses brush border → lymphatics/lymph nodes → blood (1º bacteremia) → liver, spleen

3. Survive & multiply within MΦ’s of liver & spleen (facultative intracellular parasite) → 2º

bacteremia/septicemia → enteric/typhoid fever, inflammation of Peyer’s patches (GI sx)

4. In some hosts (i.e. Typhoid Mary), hide out in gall bladder – asymptomatic but infectious

 S. enteriditis:

1. Invades mucosal cells of small intestine

2. Cholera-like toxin → watery diarrhea

3. Ileal inflammation → mucous/bloody diarrhea

 S. choleraesuis: bacteremia → brain, lungs, & bone (asplenic pts prone to osteomyelitis)



Clinical:

 Enteric (typhoid) fever (S. typhi):

 Sx (slow onset): fever, headache, abdominal pain, rash (rose spots) on abdomen

 Complications: splenic rupture, intestinal hemorrhage

 Dx: stool culture

 Rx (intracellular!): chloramphenicol (50S rRNA inhibitor), ceftriaxone (3rd gen. cephalosporins),

new floroquinolones, i.e. cipro (DNA gyrase inhibitor)

 Gastroenteritis (S. enteriditis):

 2-day incubation

 N/V/D (diarrhea may be watery or with mucous & blood)

 Dx: stool culture

 Rx: self-limiting (≤1 week); fluid & electrolyte replacement

 Hosts prone: asplenic (i.e. SCA pts.), ↓gastric acid production (Salmonella is acid-sensitive)





SHIGELLA



Structure/ID:

 Gram (-) rods, aerobic

 Non-motile (Shigella has no flagella)

 (-) Lactose fermentation (colorless on MacConkey)

 (-) H2S

 O Ag different between species: S. dysenteriae (A), S. flexneri (B), S. boydii (C), S. sonnei (D)

 S. dysentariae most often causes dysentery, but S. sonnei most common in industrialized world







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Virulence factors:

 Type III secretion organelle

 ICS-A protein → actin tail formation → movement from cell to cell (Listeria do this too!)

 σ factor of RNA polymerase: adapts to acidic environment

 Shiga toxin (like EHEC toxin) – AB toxin inhibits 60S rRNA → ↓protein synthesis → cell death



Pathogenesis:

1. Fecal-oral transmission (water, hand-to-hand)

2. Passes through stomach (thanks to σ factor), multiplies in small intestine

3. Invades intestinal epithelial cells by inducing ruffling/phagocytosis (type III secretion)

4. Multiplies in cytoplasm

5. Uses host proteins to form actin tails → form protrusions at membrane → engulfed by adjacent cell

6. Lysis of membrane → inflammatory cytokine response (so (+) fever)

7. Inflamed colon unable to reabsorb ions/fluid → diarrhea

8. Cell death from Shiga toxin & immune response → capillary thrombosis → bloody diarrhea



Clinical:

 Sx: fever, dysentery (bloody diarrhea with WBCs/pus), cramping abdominal pain

 Dx: stool culture

 Rx (intracellular!): 3rd generation cephalosporins (β-lactamase resistant), TMP/SMX (THF inhibitors),

floroquinolones (DNA gyrase inhibitors)





VIBRIO CHOLERA



Structure/ID:

 Gram (-) rod, aerobic/facultative

 Motile (single polar flagellum)

 (-) Lactose fermentation (colorless on MacConkey)

 (+) Oxidase



Virulence factors:

 Choleragen (cholera toxin) – AB toxin → ↑Gs → ↑AC → ↑cAMP → ↓ Na+/Cl- reabsorption, ↑Cl- &

HCO3- secretion (does not cause cell damage or invade) – similar to ETEC’s LT toxin

 Adhesins on pili/fimbriae (toxin coregulated pilus (TcpA))



Pathogenesis:

1. Fecal-oral transmission (water, food, seafood)

2. Release cholera toxin → ↑TcpA adhesions → binds to brush border of small intestine → multiplication

3. Cholera toxin → ↑cAMP → ↓ Na+/Cl- reabsorption, ↑Cl- & HCO3- secretion → watery diarrhea



Clinical:

 Sx: high-output watery (“rice water”) diarrhea → severe dehydration may → death; NO fever

 Dx: stool culture, serology

 Rx: oral rehydration solution, doxycycline (inhibits 30S rRNA) may shorten duration





ESCHRECHIA COLI



Structure/ID:

 Gram (-) rod, aerobic

 Motile (flagella)

 (+) Lactose fermentation (85-95%) – pink on MacConkey, metallic green on EMB agar

 Ags: O (cell wall) – highly variable, K (capsule around O (= Vi Ag)), H (flagella)

 > 4 pathogenic strains (different virulence factors): ETEC, EHEC (O157:H7), EIEC, EPEC





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Virulence factors:

 LPS (endotoxin released on lysis)

 Adhesins on pili

 ETEC: LT (like cholera toxin)/ST – AB toxins → ↑Gs → ↑AC(LT)/GC(ST) → ↑cAMP/cGMP →

↓Na+/Cl- reabsorption, ↑Cl- & HCO3- secretion (does not cause cell damage or invade)

 EHEC: Shiga-like toxins (Stx1/Stx2) – AB toxins inhibit 60S rRNA → ↓protein synthesis → cell death

 EIEC: type III secretion organelle, maybe a little Stx

 EPEC: intimin & other proteins → non-intimate attachment & effacement



Pathogenesis:

 Fecal-oral transmission

 Nonpathogenic E. coli (normal flora) + virulence factors = pathogenic E. coli

 ETEC:

1. Pili adhesins bind intestinal epithelial cells

2. Releases LT/ST → ↑AC(LT)/GC(ST) → ↑cAMP/cGMP → ↓Na +/Cl- reabsorption, ↑Cl- & HCO3-

secretion → watery diarrhea (like cholera)

 EHEC (O157:H7):

1. Pili adhesins bind intestinal epithelial cells

2. Release Stx1/Stx2 → inhibit 60S rRNA → ↓ protein synthesis → cell death → capillary

thrombosis → hemorrhagic colitis, renal endothelial damage (hemolytic-uremic syndrome)

 EIEC:

1. Invades intestinal epithelial cells by inducing ruffling/phagocytosis (type III secretion)

2. Stimulates inflammatory response → bloody diarrhea with WBCs (like Shigella)

3. May secrete a little Stx → cell death

 EPEC:

 Complex mechanism (alters cytoskeletal proteins) to form localized attaching & effacing lesions

in small intestine → watery diarrhea (mostly in infants)



Clinical:

 ETEC:

 1-2 day incubation; 3 day – several week duration

 Traveler’s diarrhea – “rice water”, no fever (no invasion)

 Dx: stool culture

 Rx: oral rehydration

 EHEC:

 3-4 day incubation; 1 week duration

 Hemorrhagic colitis – bloody diarrhea, abdominal cramping, NO fever

 Hemolytic-uremic syndrome (8-11%, usually children) – hemolytic anemia, thrombocytopenia,

thrombosis of glomerular capillaries → renal endothelial damage → acute renal failure may →

death

 Dx: stool culture

 Rx: fluids, dialysis if needed, supportive (antibiotics may ↑LPS release → ↑HUS)

 EIEC:

 <24 hour incubation

 Sx: blood and pus in stool, fever (like Shigella)

 Dx: stool culture

 Rx: ??

 EPEC:

 1-3 day duration

 Sx: watery diarrhea

 Rx: oral rehydration

 UTI (#1 cause)

 Sx: dysuria, frequency, fullness/urge

 Compications: cystitis, pyelonephritis





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 Rx: TMP/SMX (inhibit THF)

 Meningitis in neonates (2nd to group B strep)

 Rx: ampicillin (cell wall) + cefotaxime (3rd generation cephalosporin – β-lactamase resistant)

 Nosocomial infections:

 Pneumonia

 Septic shock (from LPS endotoxin) – Rx: aminoglycoside (30S rRNA) + 3rd gen. cephalosporin





ANTHRAX (BACILLUS ANTHRACIS):



Structure/ID:

 Gram (+) rod, encapsulated (only bacterium with amino acid capsule), forms chains

 Spore-forming, aerobic



Virulence factors:

 Glutamic acid capsule (encoded on plasmid PXO2) – prevents phagocytosis of vegetative form

 Spore – resistant to drying, heat, UV light, disinfectants; can survive many years in soil

 Anthrax toxin (3 proteins encoded on plasmid PXO1):

 Edema factor (EF) – like AC → ↑cAMP → ↓ PMN function, ↑edema

 Protective antigen (PA) - ↑ entry of EF & LF into phagocytic cells (like B subunit)

 Lethal factor (LF) - ↑MΦ → TNF-α, IL-1, IL-6 → inflammatory response → death



Pathogenesis:

 Cutaneous:

1. Skin contact with spore in soil (or terrorist letter)

2. Spores germinate on skin abrasions; activated at 37ºC to express PXO1 & PXO2 virulence factors

3. Rapidly multiplies and releases exotoxin → necrotic ulcer

4. May spread to bloodstream (bacteremia)

 GI (rare but deadly):

1. Ingestion (from contaminated meat)

2. Multiplies and releases exotoxin in mouth/esophagus or terminal ileum/cecum → necrotic ulcer

 Inhalational:

1. Inhaled from animal hides (or terrorist letter)

2. Spores taken up by MΦ’s in lungs → hilar & mediastinal lymph nodes (germinate there)

3. Release exotoxin → hemorrhage, pleural effusion



Clinical:

 Cutaneous (malignant pustule):

 Painless necrotic (black) ulcer with edema 3-10 days s/p exposure

 20% progress to bacteremia

 Dx: lab ID

 Rx: cipro (inhibit DNA gyrase) or doxycycline (inhibit 30S rRNA)

 GI:

 Sx: abdominal pain, vomiting, bloody diarrhea

 Rx: penicillin, doxycycline, cipro/levofloxacin

 Inhalational (Woolsorters disease):

 Fever, chills, sweats, fatigue, chest pain, cough (no purulent sputum) 1-7 days s/p exposure

 Progresses to: hemorrhagic meningitis, mediastinal hemorrhage (see widening on CXR), pleural

effusions, respiratory failure, shock

 Dx: clinical findings, lab ID

 Rx: 60 days cipro or doxycycline IV; clindamycin (inhibits 50S rRNA) to ↓ toxin production if

widened mediastinum or bacteremia/shock; add drugs for meningitis (rifampin, vancomycin, etc.);

note: lots of bugs → β-lactamase production → penicillin resistance

 Anthrax Vaccine Adsorbed (AVA): PA protein from toxin – immunogenic







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TUBERCULOSIS (MYCOBACTERIUM TUBERCULOSIS):



Structure/ID:

 Acid-fast rods – show up red on blue background, due to lipids (mycolic acids) in cell wall

 Obligate anaerobe

 Grows slowly on culture media, (+) niacin test

 Cell wall lipids: mycolic acid, mycosides (FA + carbohydrate), cord factor, sulfatides, wax D



Virulence factors:

 Cell wall lipids – survival inside MΦ’s (facultative intracellular), granuloma formation

 Cord factor → ↑TNF-α → cachexia

 Sulfatides – inhibit phagosome/lysosome fusion → survival in MΦ’s

 Wax D – adjuvant

 σ-factors – induce expression of genes involved in survival within granulomas

 Drug resistance plasmids!



Pathogenesis:

 1º infection:

1. Aerosol; inhaled (transmission by respiratory droplet)

2. Droplet → middle & lower lobes of lung (highest air flow)

3. Pneumonitis with PMNs & edema → alveolar MΦ response → phagocytosis

4. Bugs multiply in MΦ’s → bloodstream → lymph nodes → organs (especially liver & spleen)

5. Immune response:

 (+) CMI → DTH response → small caseous granuloma formation → asymptomatic

 (-) CMI (kids, elderly, immunocompromised) → large granulomas → progressive disease or

miliary TB (disseminated disease)

 Latency: bugs hanging out within caseous granulomas; reactivated when ↓CMI

 2º infection (5-10% lifetime risk for normal hosts; 8-10% annual risk for HIV (+) hosts): form

granulomas in lungs (upper lobe – ↑O2 tension) & other organs



Clinical:

 Dx of old 1º infection:

 PPD (TB → DTH response) – note: HIV+ pts may not have DTH, so test Candida or mumps too

 CXR: see calcified tubercle (Ghon focus) in lower lung, calcified granulmoa (Ghon/Ranke

complex) in hilar lymph node, or scarring in upper lobe

 Dx of active infection:

 CXR: see cavitary lesions with air fluid levels in lung

 (+) Sputum culture, acid-fast stain

 Clinical picture of active infection:

 Pulmonary TB – apical areas (↑O2 tension); sx: productive cough/hemoptysis, chronic low-grade

fever, night sweats, weight loss/cachexia → death in 50% if untreated

 Pleural/pericardial infection

 Lymph node TB = scrofula

 Kidney (“sterile pyuria”) – see RBCs/WBCs in urine, but no bacteria (slow growing)

 Skeletal/joints – destruction of T- and L-spine intervertebral discs (Pott’s disease); arthritis

 CNS – subacute meningitis, granulomas in brain

 Miliary TB – disseminated (may see millet-seed pattern in lung on CXR)

 Immunocompromised hosts more likely to develop extrapulmonary TB

 Rx: isoniazid (INH), rifampin, pyrazinamide in combo – all are hepatotoxic and may → hepatitis

 MDR TB is a huge problem, especially in HIV+ pts









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PNEUMOCOCCUS (STREP PNEUMONIAE):



Structure/ID:

 Gram (+) diplococcus (lancet-shaped), encapsulated

 α-hemolytic, (+) optochin-sensitivity

 (+) Quelling reaction (antiserum causes capsule to swell)

 Normal flora of nasopharynx; causes problems in cavities/tubes (but does not invade cells)

 84 capsular serotypes (reinfection possible)



Virulence factors:

 Polysaccharide capsule – inhibits phagocytosis & complement

 IgA protease – inhibits mucosal immunity

 C-substance – targeted by C-reactive protein → acute phase response



Pathogenesis (pulmonary disease):

1. Transmitted via respiratory droplets (inhaled)

2. Proliferate in alveoli

3. Activate compliment & cytokines

4. Alveoli fill with bugs & inflammatory cells



Clinical:

 Pneumonia (#1 cause in adults)

 Sx: sudden onset of high fevers, shaking chills (rigors), chest pain on respiration, dyspnea, cough

productive of yellow-green sputum

 Dx: may see lobar infiltrate (middle R, lower L) on CXR, clinical picture, sputum culture

 Rx: some resistance to penicillin, erythromycin, chloramphenicol, TMP/SMX; try high-dose

penicillin or cephalosporins (β-lactamase resistant); vancomycin if highly resistant

 Meningitis (#1 cause in adults)

 Otitis media/sinusitis (#1 cause in kids)

 Vaccine (pneumovax) – 25 most common capsular Ags for immunocompromised pts; new 7-Ag

vaccine for kids (100% effective in preventing invasive infections)





GONOCOCCUS (NEISSERIA GONORRHEAE):



Structure/ID:

 Gram (-) diplococci (kidney bean shaped), encapsulated

 Aerobic, oxidase (+), ferments glucose

 Grow best on Thayer-Martin VCN medium (chocolate agar with abx) & in CO2-enriched environment



Virulence factors:

 Polysaccharide capsule

 Pili & outer membrane proteins – attach to reproductive epithelium, prevent phagocytosis by staying

close to host cells

 Antigenic variation of pili & OMPs to evade Abs

 LPS endotoxin

 IgA protease



Pathogenesis:

1. Transmitted by sexual contact or during childbirth

2. Infects columnar epithelium of cervix (♀) or mucous membranes of urethra (♂)

3. Phagocytized by professional APC in submucosa, presented to CD 4+ T-cells

4. Inflammatory response initiated → symptoms









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Clinical:

 Gonorrhea in ♂:

 Urethritis → painful urination, purulent urethral discharge

 Complications: epdidymitis, prostatitis

 Gonorrhea in ♀:

 Urethritis → painful/burning urination, purulent urethral discharge – or asymptomatic

 Cervicitis → lower abdominal discomfort, dyspareunia, purulent vaginal discharge

 Complications: PID – endometritis, salpingitis and/or oophoritis – (sx: fever, lower abdominal

pain, bleeding, CMT) → sterility, ectopic pregnancy, abscesses, peritonitis, peri-hepatitis (Fitz-

Hugh-Curtis syndrome)

 Dx: culture of infected area – see Gram (-) diplococci within WBCs

 Rx: cipro or ceftriaxone (resistance to others); treat for chlamydia too (doxycycline/azithromycin)

 Complications of both:

 Bacteremia (sx: fever, joint pains, skin lesions on extremities) → peri/endocarditis, meningitis

 Septic arthritis (1 or 2 joints at first → progressive); dx: culture of synovial fluid

 Infants: ophthalmia neonatorum → damages cornea → blindness; give erythromycin eyedrops





ENTEROCOCCUS



Structure/ID:

 Gram (+) cocci

 (+) growth in 6.5% NaCl, (+) growth in 40% bile (bile esculin hydrolysis)



Virulence factors:

 Part of normal intestinal flora – only when they get out do they cause a problem

 Most infections are nosocomial



Clinical:

 UTIs

 Biliary tract infections

 Subacute bacterial endocarditis (SBE)

 Wound infections

 Bacteremia

 Rx: Ampicillin + aminoglycoside – but now many resistant; use vancomycin – but VRE now (cell wall

dAla-dAla → dAla-lactate – eliminates vancomycin target); try older abx or new pristinomycins





STREP PYOGENES



Structure/ID:

 Gram (+) streptococci, encapsulated

 Group A Lancefield Ag, β-hemolytic

 (-) Catalase, (+) bacitricin susceptibility

 Normal flora of skin and mucous membranes (especially oropharynx)



Virulence factors:

 Streptolysin O – hemolysin (→ β-hemolysis); anti-streptolysin O Abs measured by ASO titer

 M protein (80 types) – inhibits phagocytosis and complement activation (but B-cells make Ab to it)

 Hyaluronic capsule – inhibits attachment of phagocytes

 Erythrogenic/pyrogenic exotoxins (especially A) → scarlet fever, TSS

 Streptokinase – catalyzes plasminogin → plasmin → degrades fibrin → tissue degredation

 Protein F and lipoteichoic acid (LTA) – binds fibronectin on respiratory epithelial cells









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Pathogenesis:

1. Transmitted by respiratory droplets or contact with skin/fomites (sometimes in food)

2. Binds fibronectin on epithelial cells via protein F & LTA

3. Spread/multiplication:

 Impetigo – localized in skin

 Pharyngeal infection – localized, may → bacteremia

 Necrotizing fasciitis – moves rapidly through fascia (thanks to streptokinase & M proteins)

4. Exotoxin release:

 Erythrogenic/pyrogenic exotoxins (superAgs) → ↑ TNF-α, IL-1 → scarlet fever, TSS

5. Complications (acute rheumatic fever, acute glomerulonephritis) may be due to autoimmune cross-

reactivity and/or immune complexes



Clinical:

 Pharyngitis:

 Sx: beefy red tonsils with exudates, fever, NO cough, lymphadenopathy

 Dx: throat culture (note: rapid strep test has poor sensitivity – false (-)’s)

 Rx: penicillin (within 10 days to prevent rheumatic fever)

 Scarlet fever:

 Sx: fever, rash on trunk/neck → extremities (NOT on face); skin may scale during healing

 Rx: penicillin

 Skin infections:

 Impetigo (vesicular blister → crusty; often around mouth), cellulites, folliculitis

 Rx: could be caused by staph, so use dicloxacillin (penicillinase-resistant)

 Necrotizing fasciitis:

 Sx: inflammation moving away from initial site; then skin color changes from red → purple →

blue; large blisters (bullae) form; later – skin necrosis, myositis

 Rx: rapid penicillin G (IV) + clindamycin (↓ toxin production)

 TSS:

 Sx: fever, diffuse erythematous rash, N/V/D, septic shock

 Rx: penicillin G (IV) + clindamycin (↓ toxin production)

 Acute rheumatic fever (ARF):

 Complication of untreated strep pharyngitis (but not skin infection)

 Sx: fever, myocarditis, joint swelling, chorea, subcutaneous nodules, erythema marginatum (red

margin) rash

 Valvular disease develops later

 Rx: prophylactic penicillin; if (+) valvular disease – amoxicillin for dental work

 Acute glomerulonephritis (AGN):

 Complication of strep pharyngitis or skin infection (penicillin may not prevent it)

 Caused by only a few nephritogenic M-types

 Sx: smokey or tea-colored urine (hematuria), puffy face, ↑BP





STAPH AUREUS



Structure/ID:

 Gram (+) cocci in clusters

 β-hemolytic, (+) catalase, (+) coagulase

 Non-spore forming, but fairly resistant to heat & drying

 Normal flora on skin & in nares



Virulence factors:

 Factors that screw up our defenses:

 Protein A – binds IgG Fc → ↓ complement activation

 Coagulase – prevents phagocytosis





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 Hemolysis & leokocidins – destroy RBCs & WBCs

 Penicillinase & novel PBP – penicillin resistance

 Factors that tunnel through tissues:

 Hyaluronidase – hydrolizes CT (works with exfoliative toxin)

 Staphylokinase – lysis fibrin → tissue degredation

 Lipase & protease – do just what it sounds like

 Toxins:

 α-toxin – cellular destruction/abscess formation

 Exfoliative toxin – splits epidermis at stratum granulosum (works with hyaluronidase)

 TSS toxin → ↑IL-1, IL-2

 Enterotoxins – resistant to heat & gastric acid



Pathogenesis:

 Transmission: contact with skin or fomites, ingestion of exotoxin

 Usually remains localized → inflammatory response at site

 May release exotoxin → gastroenteritis, TSS, scalded skin syndrome

 May → blood (bacteremia) → sepsis

 May invade other organs (lungs, meninges, bones, etc.)



Clinical:

 Skin infections (contained):

 Impetigo, cellulitis, local abscesses, furuncles (subcutaneous), carbuncles (when furuncles join)

 Wound infections (especially post-surgical) → abscess/cellulitis; must reopen

 Rx: dicloxacillin (penicillinase-resistant) – covers Strep too

 Exotoxin release diseases:

 Gastroenteritis – ingested enterotoxin→ ↑peristalsis → N/V/D, abdominal pain, fever? (12-24 hrs)

 TSS – fever, diffuse erythematous rash, N/V/D, septic shock; must clean infected area

 Scalded skin syndrome – exfoliative toxin → cleavage of middle epidermis, skin peeling – usually

in kids (especially neonates s/p severed umbilicus)

 Rx: abx may help with TSS, but mostly supportive therapy

 Bacteremia: often from catheter (IV) → sepsis, endocarditis

 Organ invasion diseases:

 Lobar pneumonia – nosocomial, usually follows viral flu → cavitations, effusions, empyema (pus)

 Meningitis/cerebritis/brain abscess – fever, CNS sx

 Osteomyelitis – usually in boys <12 y/o; inflammation over bone, fever

 Acute endocarditis – high fever, chills, myalgias; cause valvular destruction & embolism of

vegetations → brain (L side valve) or lung (R side valve – often IV drug users)

 Septic arthritis (#1 cause) – inflamed joint, septic synovial fluid with ↑PMNs

 Rx: methicillin, nafcillin (penicillinase-resistant)

 MRSA:

 Resistance via plasmid (most encode altered PBPs)

 Nosocomial – transferred from pt to pt by us

 Use vancomycin for critical infections only (due to emergence of VRE)









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