StreptococciStreptococciClassification of StreptococciClassification of StreptococciPhylogenetic analysis 16S RNAGroup A StreptococcusTransmission / EpidemiologyClinical manifestationsLocal infectionsLocal infectionsLocal infectionsInvasive diseaseInvasive diseasePost-infectious sequelaeStreptococcal virulence factorsM protein and M-like proteinsStreptococcal virulence factorsStreptococcal virulence factorsStreptococcal virulence factorsRegulation of virulence genesDiagnosis / Treatment / PreventionStreptococcus pneumoniaeTransmission / EpidemiologyClinical manifestationsPneumoniaMax - Pediatric respiratory tract infectionsAcute otitis mediaPneumococcal diseaseSteps in pathogenesisPneumococcal virulence factorsSlide 31DiagnosisTreatmentPreventionClassification of StreptococciGroup B StreptococcusEnterococcus (Group D strep)Enterococcus (Group D strep)Treatment/PreventionViridans StreptococcusViridans streptococciS. mutans biofilm formationStreptococcal endocarditisStreptococciStreptococciMIC 301, Feb 8, 2013Anders Hakansson, Ph. D.StreptococciStreptococci•Streptococci are ★Gram-positive★Cocci (spherical or ovoid) occurring in pairs and chains. ★Catalase-negative (which differentiate them from Staphylococci).★Facultative anaerobes = primarily fermenters that can tolerate oxygen•Primarily uses lactic acid fermentation - anaerobic pathway(pyruvate + NADH -> lactic acid + NAD+)★Some bacteria produce only lactic acid (homolactic fermenters)★Other bacteria produce other products as well; ethanol, acetate, formate, butanediol (heterolactic fermenters).Classification of StreptococciClassification of Streptococci*usually non-hemolytic, but may be alpha or beta hemolyticHemolytic pattern(Group D)*Classification of StreptococciClassification of StreptococciLancefield group Representative species InfectionsA S. pyogenesPharyngitisSkin/soft tissue infectionB S. agalactiaeNeonatal pneumoniaSepsisCS. equi, equisimilisURIDEnterococcus faecalis, faeciumS. bovis, equinusUTIEndocarditisFS. anginosus AbscessesGS. canisCellulitisViridans group(no antigen)S. mutans, mitis, salivarius, thermophilus, sanguinisCariesEndocarditisNo antigen S. pneumoniae Pneumonia, meningitisOtitis media, sepsisPhylogenetic analysis 16S RNAPhylogenetic analysis 16S RNA(A, B, C)(F)(viridans)(viridans)(viridans)(D)Group A StreptococcusGroup A Streptococcus•Gram-positive, beta-hemolytic coccus that grows in chains•Expresses the group A carbohydrate (N-acetyl--D-glucosamine linked to poly-rhamnose)•Given the name Streptococcus pyogenes, based on its purulent infections in 1884 by Dr. Rosenbach.http://www.life.umd.edu/classroom/bsci424/Images/PathogenImages/StreptococcusSEM.jpgScanning EM Gram stainingTransmission / EpidemiologyTransmission / Epidemiology•Asymptomatic colonization is common★Oropharynx★Respiratory tract★Skin•Mostly affects children 1-15 years of age•Transmission via droplets, facilitated by many people in a shared environment (day cares, schools etc)•“Strep throat” often recurring even after antibiotic treatmentClinical manifestationsClinical manifestations•Asymptomatic carriage / Colonization•Localized infection★Pharyngitis (“Strep throat”)★Scarlet fever (rash)★Impetigo (superficial skin infection)★Cellulitis / erysipelas (deeper skin infection)•Invasive infection★Bacteremia★Streptococcal toxic shock syndrome (rash, fever, edema)★Necrotizing fasciitis (“flesh-eating infections”)•Post-infectious sequalae★Acute rheumatic fever (arthritis and endocarditis)★GlomerulonephritisJim Henson died from GAS infectionLocal infectionsLocal infections•Pharyngitis (“Strep throat”)★GAS are the most common bacterial cause of pharyngitis in children 1-15 years of age.★Strains that cause pharyngitis tend not to cause skin infections and vice versa.★M types 1, 3, 5, 6, 14, 18, 19, 24★Important sequelae is rheumatic fever (up to 3% of patients).★Sequelae with arthritis, endocarditis, CNS symptoms, skin lesions and subcutaneous nodules seen.★Symptoms: chills, fever, headache, red pharynx with exudate, anterior cervical lymphadenitis.Local infectionsLocal infections•Scarlet fever (rash)★Disease of childhood caused by GAS exotoxins★Symptoms: sore throat, fever, diffuse rash “Strawberry” tongueLocal infectionsLocal infections•Impetigo (superficial skin infection)★Skin infection usually seen in children.★Histological evidence of 1-2 mm vesicles that evolve into pustules which eventually crust – typically below nares or under lip.★Regional adenopathy without systemic symptoms.★Untreated impetigo can be self-limiting, but can lead to glomerulonephritis as well as sepsis.•Cellulitis (deep skin infection)★Most people with cellulitis feel only mildly ill, but some may have a fever, chills, rapid heart rate, etc.★Local lymphadenitis★Can lead to sepsis.Invasive diseaseInvasive disease•Bacteremia•Streptococcal toxic shock syndrome (rash, fever, edema)★Symptoms: Fever, skin rash (can be confused for scarlet fever), shock (hypotension) and multiple organ failure.★Death rate approx 30%.★Induced by streptococcal superantigens = nonspecific activation of T cell receptors  polyclonal activation of T cells  Cytokine storm ★Can lead to necrotizing fasciitis.Invasive diseaseInvasive disease•Necrotizing fasciitis (“flesh-eating infections”)★Hypotension, shock, multiple organ failure, rapid necrosis of fascia and skin, gangrene.★Infection around a cut or bruise that is much more painful than expected with high fever.★Area of infection spreads up the affected arm, leg, or other body part very quickly - as fast as 1 inch per hour★High mortality ratePost-infectious sequelaePost-infectious sequelae•Acute rheumatic fever (arthritis and endocarditis)★Sequalae after pharyngitis.★The risk of developing rheumatic fever following untreated tonsillopharyngitis is 1-3% in the civilian population.★The causal strain adheres to the oral and pharyngeal cells and then releases its degradation products which cross-react with certain human tissues particularly in cardiac valve and myocardium tissue. ★Symptoms: Fever, painful joints, chest pain, fatigue, rapid fluttering heartbeats.•Glomerulonephritis★Sequalae after skin infection and pharyngitis★Glomerulonephritis develops ~10 days after pharyngitis or 2 weeks after impetigo with a nephritogenic strain of GAS★Symptoms: Patients present with gross