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
1
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
2
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- & HCO3secretion → 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
3


 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
4
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
5
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
6
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 (FitzHugh-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
7
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 crossreactivity 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
8


 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)
9