STREPTOCOCCUS ENTEROCOCCUS - medsyllabus.org · Pharyngitis (& tonsilitis): Scarlet fever: ......
Transcript of STREPTOCOCCUS ENTEROCOCCUS - medsyllabus.org · Pharyngitis (& tonsilitis): Scarlet fever: ......
STREPTOCOCCUS
&
ENTEROCOCCUS
REVIEW
Bacterial Cell Morphology• Gram Stain• Cytoplasmic (plasma) membrane • Cell wall structure• Bacterial cell shapes
Common Cell Membrane
Gram-Positive Cell Wall
Gram-Negative
Gram-Positive
Peptidoglycan
Teichoic Acid
Gram-Positive Cell Wall
Gram-Negative Cell Wall
Gram-Negative Cell Wall
Genus Streptococcus
Commensals or Parasites of man & animals or
Saprophytes of decaying matter
MorphologyGram-Positive Cocci in Pairs or Chains
Gram-PositiveStreptococcus
Genus Streptococcus
Physiology & MetabolismFacultative AnaerobesFastidious Growth RequirementsFermentative Metabolism of Carbohydrates:
Lactic acid, ethanol, acetate endproducts produced; No gasCatalase Negative (2H2O2 ---> O2 + 2H2O)
Separation of streptococci from staphylococciOxidase Negative (oxidoreductase oxidizes substrate w/ O2)
Beta, Alpha, or Gamma Hemolysis on blood agar
Genus StreptococcusRebecca Lancefield
Developed useful serogrouping system Classification of beta-hemolytic streptococci by group-specific cell wall carbohydrate (CHO) antigen As of 1992, Serogroups A to H and K to V
Groups A, B, C, D, and G are most comonly associated with human diseaseViridans streptococci and Streptococcus pneumoniae have no group-specific antigen
Antigenic StructureStreptococcus pyogenes (Group A)
Lancefield Group-specific antigen (C polysaccharide)Complex polysaccharide in cell wall
Proteins: Two major classes, M & T antigens Two minor classes, R & F
M-Protein: Type-specific antigen Fimbriae-like, hairy extensions
Resistant to heat and acid Trypsin Sensitive
Specific adherence by lipoteichoic acid and M-protein • (LTA-M) complexes
Antigenic StructureStreptococcus pyogenes (Group A)
Lancefield Group-specific antigen (C polysaccharide)Complex polysaccharide in cell wall
Proteins: Two major classes, M & T antigens Two minor classes, R & F
M-Protein: Type-specific antigen Fimbriae-like, hairy extensions
Resistant to heat and acid Trypsin Sensitive
Specific adherence by lipoteichoic acid and M-protein (LTA-M) complexes
T Antigens (not virulence factor)Resistant to trypsin, heat and acid; Adjunct to M-typing; Routine surveillance
Others
Antigenic Structure (cont.) Streptococcus pyogenes (Group A)
Capsular Polysaccharide: Hyaluronic acidNot present in all strainsSame as host hyaluronic acid (cartilage,skin etc)NonimmunogenicAntiphagocyticHyaluronidase (cell wall division) during late growth
Lipoteichoic Acid
Lancefield Serogroup Classification of Beta-Hemolytic Streptococci Important in
Human Disease
Group A Streptococci:Streptococcus pyogenes
• One of Most Important Human Pathogens• Suppurative Diseases:
Pharyngitis; Scarlet Fever; Cutaneous & Soft Tissue InfectionsSystemic Disease
• Non-Suppurative Sequelae:ARF,RHD,AG
Streptococcus pyogenes
(Phase Contrast)
Lancefield Serogroup Classification of Beta-Hemolytic Streptococci Important in
Human Disease (cont.)
Group B Streptococci: Streptococcus agalactiae
•Neonatal disease & obstetric complications
•Systemic, Cutaneous, UTI's
Streptococcus agalactiae
Lancefield Classification of Beta-Hemolytic Streptococci (cont.)
Group C Streptococci: Pharyngitis
Group G Streptococci:S.anginosus-milleri grp; Streptococcus spp.Pharyngitis Non-Lancefield Group Streptococci
Viridans StreptococciDental Caries: Streptococcus mutansStreptococcus sanguis; Streptococcus salivarius; Streptococcus mitis
Streptococcus pneumoniae
Enterococcus & Group D StreptococciGenitourinary Tract Infections (UTIs)Endocarditis
Major Human Diseases of Beta-Hemolytic Streptococci
Group A Streptococcus (S. pyogenes):Diverse group of acute suppurative (pus-forming) & nonsuppurative diseases
Suppurative Streptococcal DiseasesPharyngitis (& tonsilitis):
Scarlet fever: Complication of streptococcal pharyngitis when infecting strain is lysogenized; Frequently develop scarletina rash on upper chest spreading to extremities
Cutaneous & Soft Tissue Infxns.Pyoderma (Impetigo: contagious pyoderma with superficial yellow weeping lesions)Erysipelas: Acute superficial cellulitis of skin with lymphatic involvement; face and lower extremities, skin and subcutaneous tissues
Erysipelas
NOTE:√ erythema
√ bullae
Major Human Diseases of Beta-Hemolytic Streptococci (cont.)
Group A Streptococcus (S. pyogenes)Suppurative Streptococcal Diseases Cutaneous & Soft Tissue Infxns(cont.)
Cellulitis: Involvement of deeper subcutaneous tissues; Deeper invasion with systemic symptoms
Necrotizing fasciitis: (a.k.a., “flesh-eating bacteria”): Infection deep in subcutaneous tissues that spreads along fascial planes, destroying muscle and fat; Initially cellulitis followed by bullae (fluid filled blisters; bulla is singular), gangrene, systemic toxicity, multiorgan failure and mortality in more than 50% of patients
Wound Infections
Suppurative Streptococcal Diseases Group A Streptococcus (cont.)
Other Suppurative DiseasesPuerperal & neonatal sepsisLymphangitis: Inflammation of lymphatic vessel(s)Pneumonia
Systemic DiseaseStreptococcal Toxic Shock
Syndrome (TSS): Multisystem toxicity following soft tissue infection progressing to shock and organ failure (not to be confused with Staphylococcal Toxic Shock Syndrome where hyperabsorbent tampons have been identified as an important risk factor)
Bacteremia
Group A Streptococcal Diseases (cont.)
Nonsuppurative Sequelae Post-infection complications of Group A streptococcal disease; Serious complications in pre-antibiotic era; still important in developing countries Acute rheumatic fever (ARF):
Inflammation of heart, joints, blood vessels, sub-cutaneous tissues
Rheumatic heart disease (RHD): Chronic, progressive heart valve damage
Acute glomerulonephritis (AG): Acute inflammation of renal (kidney) glomeruli
Foodborne Disease
Epidemiology of Acute Streptococcal Infection• Predilection for upper respiratory tract or skin•Group A commonly colonize oropharynx of healthy children• M-types of strains colonizing throat differ from those on skin• Rapidly killed after phagocytosis, but cell walls not digested and may lead to chronic inflammatory lesions
Pharyngitis transmitted by droplets from respiratory secretions• Crowding increases risk (e.g., classrooms, day care facilities)
Pyoderma transmitted by direct contact with infectious lesions
Nonsuppurative Sequelae of Acute Group A Streptococcal Infection
Acute Rheumatic Fever (ARF)Inflammatory reaction characterized by arthritis, carditis, chorea (disorder of CNS with involuntary spastic movements), erythema marginatum (skin redness with defined margin), or subcutaneous nodulesWithin 2-3 weeks following pharyngitis• Epidemic pharyngitis: ARF in as many as 3%• Sporadic pharyngitis: ARF in 1 per 1000
Morbidity & mortality linked to subsequent disease of heart valve (Rheumatic Heart Disease)
Poorly understood pathogenesis with several proposed theories including cross-reactivity of heart tissues & strep AGNs •?? (Type ?? hypersensitivity, exotoxins, direct invasion)II
Nonsuppurative Sequelae of Acute Group A Streptococcal Infection (cont.)
Acute Glomerulonephritis Follows either respiratory (pharyngitis) or cutaneous (pyoderma) streptococcal infectionAssociated with well-defined group of M-types Incidence varies from <1% to 10-15%Most often seen in children manifesting as dark, smoky urine with RBC's, RBC casts, white blood cells, depressed serum complement, decreased glomerular filtration rateLatent period: 1-2 weeks after skin infection and 2-3 weeks after pharyngitisGranular accumulations of immunoglobulin due to deposition of immune complexes within the kidney (Type ?? Hypersensitivity)III
Determinants of PathogenicityCellular Virulence Factors
Capsule Antiphagocytic; Nonspecific adherenceHyaluronic acid (polysaccharide) mimics animal tissue
Lipoteichoic AcidCytotoxic for wide variety of cellsAdherence: Complexes with M protein (LTA-M) and binds to fibronectin on epithelial cells
M-ProteinLTA-M protein is adhesinAntiphagocyticInhibits alternate C’ pathway and opsonization
M-like Proteins: bind IgM and IgGF Protein: mediates adherence
Extracellular Virulence FactorsExotoxins:
Streptolysin O (SLO): Hemolytic and Cytolytic Prototype of oxygen-labile and thiol-activated cytolytic exotoxins (e.g., Streptococcus, Bacillus, Clostridium, Listeria)Lytic for variety of cells: bind to cholesterol-containing membranes and form arc- or ring- shaped oligomers that make cell leaky (RBC's, WBC’s, PMN's, platelets, etc.) Causes sub-surface hemolysis on BAPStimulate release of lysosomal enzymesSLO titer indicates recent infection (300-500 in pediatric populations)
Extracellellular Virulence Factors (cont.)
Exotoxins (cont.):Streptolysin S (SLS):
Hemolytic and CytolyticOxygen stable, non-antigenicLytic for red and white blood cells and wall-less forms (protoplast, L- forms)Causes surface hemolysis on BAP
Lysogeny: Lysogenized bacteriophages play key role in directing synthesis of various Group A streptococcal enzymes and toxins
• Pyrogenic Exotoxin (erythrogenic toxin)
• Phage-associated muralysins (lyse cell walls) produced by both Groups A and C
Extracellular Virulence Factors (cont.)
Exotoxins (cont):Pyrogenic (Erythrogenic) Exotoxins (Types A, B &C)
Produced by more than 90% of Grp A strep Lysogeny: Structural gene is carried by temperate bacteriophage, as is the case with diphtheria toxin
Mediate pyrogenicity (fever)Causes scarlet fever (scarletiniform) rashIncrease susceptibility to endotoxic shock
Type C toxin increases permeability of blood-brain barrierEnhance DTH Mitogenic for T lymphocytes (cause cell division), myocardial and hepatic necrosis, decrease in antibody synthesisImmunomodulators (superantigens): stimulate T cells to release cytokines
Cardiohepatic toxin
Extracellular Virulence Factors (cont.)
Enzymes:
Nucleases: Four antigenic types (A,B,C,D) Facilitate liquefication of pus generating growth substratesNucleases A, C have DNase activityNucleases B, D also have RNase activity
Streptokinases: Two different formsLyse blood clots: catalyze conversion of plasminogen to plasmin, leading to digestion of fibrin
C5a Peptidase: destroys C’ chemotactic signals (C5a)Hyaluronidase: hydrolyzes hyaluronic acidOthers: Proteinase, NADase, ATPase, phosphatase, etc.
Lab Identification of S. pyogenes (Group A)
• Primary culture by pour or streak plate• Domed,grayish/opalescent colonies
• Encapsulated cells produce mucoid colonies
Beta-hemolytic • Zone several times greater than diameter of colony
TSAS. pyogenes
Lab Identification of S. pyogenes (Group A) (cont.)
Catalase Negative: Differentiates from Staphylococcus
Bacitracin test: presumptively distinguishing between Group A beta-hemolytic streptococci (bacitracin POS) and other beta-hemolytic streptococci that are isolated from pharyngeal swabs (95% sensitivity for Grp A strep)
Rapid Identification Tests: Based on extraction of Group A carbohydrate directly from throat swabs
• ELISA, Coagglutination, Fluorescent Antibody
Group B Streptococcus
Streptococcus agalactiae
Group B Streptococcal Infections
Grp B Streptococcal Infections (cont.)
Age-Specific Attack Rates of Group B Streptococcal Disease
Epidemiology of Neonatal Group B Streptococcal Disease
Group B Streptococcus S. agalactiae
Diagnostic Laboratory Tests• CAMP factor positive
• Hippurase positive
CAMP Factor TestS. aureus
(Spingomyelinase C)Group B
Streptococcus(CAMP Factor)
Group A Streptococcus
Enhanced Zone of
Hemolysis
Hippurase NEG
Hippurase POS
Grp B Streptococci
and
Campylobacter
Streptococcus pneumoniae
• Commonly referred to as pneumococcus• Formerly Diplococcus pneumoniae
Streptococcus pneumoniae Infections
Epidemiology (cont.)Pneumococcal Infections (cont.)
S. pneumoniae• Diplococcus
S. pneumoniae: lancet-shaped diplococcus
S. pneumoniae Virulence Factors
S. pneumoniae Seasonal Incidence
Comparison of Morbidity & Mortality
for Bacterial Meningitis
Genetic Variation (Mutation)
Beginning of Molecular Genetics
Transformation (In vivo) (Griffith)
Streptococcus pneumoniae
Diagnostic Laboratory Tests• Optochin sensitivity (Taxo P disc)
Optochin SensitivityTaxo P
Streptococcus pneumoniae
Enterococcus faecalis Enterococcus faecium
• GI tract of humans and animals• Group D carbohydrate cell wall antigen• Formerly Streptococcus
Enterococcal Infections
Enterococcal Infections (cont.)
➢ Important nosocomial pathogen
➢ Vancomycin resistant Enterococcus (VRE)
Enterococcus
Diagnostic Laboratory Tests• Resistant to bile• Esculin hydrolysis• BEA media
Bile Esculin AgarPOS
EnterococcusGroup D Streptococcus
Bile Esculin AgarNEG
Esculin Bile
Assay
REVIEW
Lancefield Serogroup Classification of Beta-Hemolytic Streptococci Important in
Human DiseaseGroup A Streptococci:
Streptococcus pyogenesOne of Most Important Human PathogensSuppurative Diseases: Pharyngitis; Scarlet Fever;
Cutaneous & Soft Tissue Infections; Systemic Disease
Non-Suppurative Sequelae:ARF,RHD,AGGroup B Streptococci:
Streptococcus agalactiaeSystemic, Cutaneous, UTI's Neonatal diseaseObstetric Complications REVIEW
Nonsuppurative Sequelae of Acute Group A Streptococcal Infection
Acute Rheumatic Fever (ARF)Inflammatory reaction characterized by arthritis, carditis, chorea (disorder of CNS with involuntary spastic movements), erythema marginatum (skin redness with defined margin), or subcutaneous nodulesWithin 2-3 weeks following pharyngitis• Epidemic pharyngitis: ARF in as many as 3%• Sporadic pharyngitis: ARF in 1 per 1000
Morbidity & mortality linked to subsequent disease of heart valve (Rheumatic Heart Disease)
Poorly understood pathogenesis with several proposed theories including cross-reactivity of heart tissues & strep AGNs •?? (Type ?? hypersensitivity, exotoxins, direct invasion)II REVIEW
Nonsuppurative Sequelae of Acute Group A Streptococcal Infection (cont.)
Acute Glomerulonephritis Follows either respiratory (pharyngitis) or cutaneous (pyoderma) streptococcal infectionAssociated with well-defined group of M-types Incidence varies from <1% to 10-15%Most often seen in children manifesting as dark, smoky urine with RBC's, RBC casts, white blood cells, depressed serum complement, decreased glomerular filtration rateLatent period: 1-2 weeks after skin infection and 2-3 weeks after pharyngitisGranular accumulations of immunoglobulin due to deposition of immune complexes within the kidney (Type ?? Hypersensitivity)III REVIEW
Determinants of PathogenicityCellular Virulence Factors
Capsule Antiphagocytic; Nonspecific adherenceHyaluronic acid (polysaccharide) mimics animal tissue
Lipoteichoic AcidCytotoxic for wide variety of cellsAdherence: Complexes with M protein (LTA-M) and binds to fibronectin on epithelial cells
M-ProteinLTA-M protein is adhesinAntiphagocyticInhibits alternate C’ pathway and opsonization
M-like Proteins: bind IgM and IgGF Protein: mediates adherence REVIEW
Extracellular Virulence FactorsExotoxins:
Streptolysin O (SLO): Hemolytic and Cytolytic Prototype of oxygen-labile and thiol-activated cytolytic exotoxins (e.g., Streptococcus, Bacillus, Clostridium, Listeria)Lytic for variety of cells: bind to cholesterol-containing membranes and form arc- or ring- shaped oligomers that make cell leaky (RBC's, WBC’s, PMN's, platelets, etc.) Causes sub-surface hemolysis on BAPStimulate release of lysosomal enzymesSLO titer indicates recent infection (300-500 in pediatric populations) REVIEW
Extracellellular Virulence Factors (cont.)
Exotoxins (cont.):
Streptolysin S (SLS): Hemolytic and CytolyticOxygen stable, non-antigenicLytic for red and white blood cells and wall-less forms (protoplast, L- forms)Causes surface hemolysis on BAP
REVIEW
Extracellular Virulence Factors (cont.)
Exotoxins (cont):Pyrogenic (Erythrogenic) Exotoxins (Types A, B &C)
Produced by more than 90% of Grp A strep Lysogeny: Structural gene is carried by temperate bacteriophage, as is the case with diphtheria toxin
Mediate pyrogenicity (fever)Causes scarlet fever (scarletiniform) rashIncrease susceptibility to endotoxic shock
Type C toxin increases permeability of blood-brain barrierEnhance DTH Mitogenic for T lymphocytes (cause cell division), myocardial and hepatic necrosis, decrease in antibody synthesisImmunomodulators (superantigens): stimulate T cells to release cytokines
Cardiohepatic toxin REVIEW
Extracellular Virulence Factors (cont.)
Enzymes:
Nucleases: Four antigenic types (A,B,C,D) Facilitate liquefication of pus generating growth substratesNucleases A, C have DNase activityNucleases B, D also have RNase activity
Streptokinases: Two different formsLyse blood clots: catalyze conversion of plasminogen to plasmin, leading to digestion of fibrin
C5a Peptidase: destroys C’ chemotactic signals (C5a)Hyaluronidase: hydrolyzes hyaluronic acidOthers: Proteinase, NADase, ATPase, phosphatase, etc.
REVIEW
Epidemiology of Neonatal Group B Streptococcal Disease
REVIEW
REVIEW
Streptococcus pneumoniae Infections
REVIEW
➢Infections from endogenous spread from naso- or orapharynx
➢Pneumonia; sinusitis; otitis media; bacteremia; meningitis
➢Colonization highest in children
➢Antecedent viral respiratory tract disease increases risk
➢Most common in cold months
➢Polyvalent vaccine available (newly available for children)
S.pneumoniae Virulence Factors
REVIEW
Comparison of Morbidity & Mortality
for Bacterial Meningitis
REVIEW
Genetic Variation (Mutation)
REVIEW
Beginning of Molecular Genetics
REVIEW
Transformation (In vivo) (Griffith)
REVIEW
Enterococcal Infections
REVIEW
➢Group D cell wall antigen
➢Enterococcus faecalis; Enterococcus faecium
➢GI tract of humans and animals
➢UTI most common; wound infections; bacteremia; endocarditis
➢Most infections from endogenous source
➢Prolonged hospitalization and broad-spectrum antibiotics increase risk
➢Antibiotic resistance (VRE)