Download microbiology ch 12 [9-4

Micro Chapter 12
Streptococci and Enterococci
Key Concepts
 Group A Streptococci
o Pathogen: Gram+ diplococci (or chain); ferments carbon sources to produce lactic acid
 Classified by hemolytic patterns on blood agar, serologic reaction of cell wall antigens, and
speciation based on metabolic and DNA sequence differences
o Encounter: resides in human reservoir
o Entry: GAS strict human pathogens that colonize nasopharynx and skin as portals of entry; may exhibit
asymptomatic carriage at same sites
o Spread: contact between humans who carry organism
o Multiplication: extracellular growth of organisms on mucous membranes, in skin, or in deeper tissue
o Damage: numerous extracellular toxins and surface virulence factors that mediate evasions of immune
response and cause extensive tissue damage and spread from initial site of infection
 Can result in immune-related diseases (rheumatic fever, glomerulonephritis) which persist even
after organism cleared from body
o Diagnosis: cultured from throat or detected by rapid immunoassays
o Treatment and Prevention: susceptible to penicillin; Tx prevents locally invasive infection, rheumatic
fever, and transmission to susceptible hosts; no vaccine
 Group B streptocci – strict human pathogens; leading cause of neonatal sepsis and meningitis
 Viridans streptococci – α-hemolytic species inhabiting oral cavity; can seed bloodstream and cause endocarditis
 Enterococci
o Pathogen: Gram+ cocci that grow in pairs or chains; ferment carbon sources to produce lactic acid; grow
in bile and relatively high salt concentrations
o Encounter: commensal organisms in GI tract of healthy individuals; act as opportunistic pathogens of
compromised patients in nosocomial infections
o Entry: GI or contamination of indwelling catheters by infected hands
o Spread: local but may cause transient bacteremia
o Multiplication: extracellular growth of organisms occurs in GU tract or abscesses
o Damage: possess hemolysin for human RBCs but cause relatively weak pathogens; bacteremia may
result in endocarditis
o Diagnosis: routine cultures
o Treatment and Prevention: intrinsically resistant to many antibiotics and often require synergistic
antibiotic combo to successfully treat infection; VRE increasing problem in hospitals
Classification of Streptococci and Enterococci
 Hemolytic pattern: colonies surrounded by greenish partial hemolysis (α-hemolysis); no hemolysis (γ-hemolysis);
or clear zone of complete hemolysis (β-hemolysis)
 Group-specific antigens (Lancefield classification): serological reactivity to extracted cell wall antigens (A-U)
o Many strep can’t be assigned to a group because no antisera that react to cell wall antigens
 Species: determined by performing biochemical tests that analyze metabolism and presence of enzymes
o Differentiate on basis of DNA sequences w/molecular techniques
Group A Streptococci
 Strep pyogenes; spectrum of diseases caused by GAS influenced by strain type, host factors, and portal of entry
 Ubiquitous in human population; disease most common in school-aged children 5-15 years old; primarily
represents as acute pharyngitis (strep throat)
 Infection in skin and soft tissues produces pyoderma; most prevalent in preschool children; more frequently in
hot, humid areas
 Delayed non-suppurative sequelae of GAS infection (acute glomerulonephritis (AGN) and acute rheumatic fever
(ARF)) more commonly encountered in developing countries
 Carried for months w/o symptoms, esp. in winter
 Person-to-person spread mediated by respiratory droplets or direct contact (skin)
o












Those w/nasal colonization able to transmit organisms more efficiently than people w/skin or
pharyngeal colonization
Pyoderma infections – bacteria gain entry into deeper layers of skin through direct implantation after break
Pharyngeal infections – bacteria binds to mucous membranes of pharynx using adhesins on bacterial cell surface
o M protein important adhesion to keratinocytes
o Hyaluronic acid capsule allows GAS to bind to host HA receptor (CD44) found on surface of pharyngeal
epithelial cells and skin keratinocytes
o Adhere to host ECM molecules surrounding host tissue (fibronectin and laminin) using ECM adhesins
(lipoteichoic acid, SfbI (Fba), and serum opacity factor)
Antiphagocytic factors: M protein and HA capsule; produce proteins that degrade chemotaxins that recruit
neutrophils to site of infection, inactivate or degrade antibodies, and block antimicrobial peptide function
Oropharynx – infections usually self-limiting and stay in pharynx and tonsils; rarely cause peritonsillar abscess
(quinsy) or spread to adjacent structures (mastoid air cells or middle ear)
Benign GAS skin infections result in crusty honey-colored lesions (impetigo); deeper layers cause erysipelas
(raised, bright red patch of skin w/sharply demarcated but rapidly advancing margin) and cellulitis
Rare occasions: GAS reaches fascial planes between skin and muscle as result of traumatic breach through skin
o Infection may spread rapidly and proximally from initial site of infection
o Secretes enzymes that may promote spread along tissue planes (necrotizing fasciitis and myositis)
 Enzymes include proteases, hyaluronidase, DNases, and streptokinase
 Streptokinase binds human plasminogen to form catalytic complex that converts plasminogen to
plasmin, which is then bound on GAS surface; plasmin-coated GAS degrades and gets past fibrin
(component of blood clots and barrier to microbial spread)
 Streptolysins S and O lyse membranes of various host cells; lysis of RBCs causes β-hemolysis
M protein – fibrillary coiled-coil surface protein; plays role in adhesion to keratinocytes and prevents
opsonization by complement
o Binds host cell plasma protein fibrinogen, interfering w/alternative pathway of complement deposition
by forming dense layer on bacterial surface
o Binds host complement control proteins that inhibit formation of opsonins by complement cascade
o Antibodies against hypervariable amino-terminal regions of M protein able to effectively opsonize
organism and are protective against infection
o Emm-typing = DNA sequencing hypervariable region of M protein gene; over 200 distinct M-types
HA capsule – HA found in human CT, so wrapping themselves in capsule camouflages GAS from host antigen
o Appear mucoid in culture; interferes w/adherence of GAS to epithelial cells; may need to shed capsule in
early stages of infection by digesting it w/hyaluronidase secreted by bacteria
Large variety of secreted substances causes considerable damage to host tissues (from GAS and immune syst.)
o Can cause septicemia (growing in non-immune whole blood) or toxemia (toxins alone enter bloodstream
from infected tissue sites, causing systemic effects)
Scarlet fever – toxemia associated w/pharyngeal infections; toxins responsible are streptococcal pyrogenic
exotoxins (SPE) A, B, and C
o SPE-A and SPE-C are bacterial superantigens that can nonspecifically activate large subset of T cells
o Massive release of proinflammatory cytokines by activated T cells results in sepsis-like shock and
multiorgan failure
Streptococcal toxic shock syndrome (STSS) – similar to TSS caused by Staph aureus
o SPE-A most closely linked to STSS; GAS can make other superantigens
ARF – nonsuppurative sequelae; causes valvular heart disease; follows pharyngitis
o 1-4 weeks after strep throat, get carditis, polyarthritis, chorea (dance-like movements), subcutaneous
nodules, and distinctive rash (erythema marginatum)
o Eventually all manifestations resolve; can happen if you don’t complete antibiotic course for strep
o Main reason to treat strep pharyngitis is to prevent ARF and permanent heart damage caused by it
o Once they had ARF, pts more susceptible to complications in any future strep infection
o Turbulent flow of blood across scarred or deformed valve predisposes to bacterial endocarditis
o ARF and rheumatic heart disease prevented by eradicating bacteria w/antibiotics before fulminant
immunological response mounted
o
Pts who develop ARF given prophylactic antibiotics until well into adulthood or for life to prevent repeat
strep infections that worsen any ongoing heart damage
o Autoimmune disease (immune system attacks self in attempt to eradicate strep)
o Immunological cross-reaction between GAS antigens (certain M proteins) and tissues in heart, synovium,
and neurons in brain (these strains rheumatogenic strains)
 Acute poststreptococcal glomerulonephritis (APSGN) – caused by only few M-types; may follow either
pharyngitis or pyodermal infection
o Treatment w/antibiotics doesn’t affect occurrence
o Immune complexes deposited in glomerular BM  complement fixation w/subsequent renal injury
o 1-4 weeks after strep infection
o Blood and protein in urine; may go on to renal failure and require dialysis
 Diagnosis usually made presumptively in skin infections
 Myositis and necrotizing fasciitis should be treated aggressively by IV antibiotics and surgery (rapid spread)
 Rapid strep tests – rely on detection of group A carb antigen from organisms on throat swab
o Positive test indicates presence of GAS (specific, but not sensitive)
o Strep throat not ruled out until negative throat culture found several days later
 ARF and APSCGN Dx require evidence of preceeding GAS infection; serologic titers to GAS antigens used
o Antistreptolysin O titer, anti-DNase B titer, and Streptozyme screen (agglutination test that detects
mixture of 5 secreted strep enzymes)
 Penicillin is antibiotic of choice; course of 10 days standard therapy; shorter courses don’t prevent ARF
o Alternative therapy – single-dose injection of long-acting penicillin (benzathine penicillin) that persists in
bloodstream for adequate period
o For those allergic to penicillin, use erythromycin or macrolide antibiotics (erythromycin-resistant strains)
Group B Streptococci
 Aerobic Gram+ diplococci; β-hemolytic; common inhabitants of lower GI and female genital tracts
 Generally don’t cause disease in healthy people; pathogenic in newborn infants
o Pregnant women screened 35-37 weeks of pregnancy by collection of vaginal and rectal swabs; if
positive, intrapartum antibiotics given to mother to reduce risk of transmission to infant
o Leading cause of neonatal sepsis and meningitis
o Surviving infants have seizures, deafness, developmental delay, and motor deficits
 In pregnant women, GBS causes UTI, endometriosis, and amnionitis
 Elderly w/DM, liver disease, renal disease, or malignancy more susceptible; penicillin-susceptible
 Evades opsonization and phagocytosis by elaboration of polysaccharide capsule; 9 serotypes (type III responsible
for majority of cases of neonatal sepsis and meningitis)
o Capsular antigens poor antigens for stimulating protective immune response
Other Pathogenic Streptococci
 Groups C and G strep (S. dysgalactiae) – β-hemolytic; disease manifestations include respiratory and deep tissue
infections; nonsuppurative sequela of AGN
o Have M proteins, adhesins, and streptokinase
 Viridans streptococci – primarily α-hemolytic species found in oral cavity
o S. mutans and S. sobrinus important components of dental plaque (produce lactic acid during
metabolism of sugars, causing dental caries)
o Most viridans strep can intermittently seed bloodstream, leading to endocarditis in people w/defective
heart valves (including those w/ARF)
o S. milleri in anginosus group; anaerobic; often involved in polymicrobial abscesses of brain, liver, and
abdominal cavity
 Nutritionally variant streptococci – difficult to grow in lab because of required supplemental cofactors
o Cause destructive form of endocarditis that results in more complications than infections w/other strep
Enterococci
 E. faecalis and E. faecium – cause UTIs, wound infections, endocarditis, intra-abdominal abscesses, and
bacteremia; part of normal flora of GI and GU tracts





Develop resistance to many types of antibiotics: penicillins merely bacteriostatic; cephalosporins don’t work at
all; intrinsically resistant to aminoglycosides; treat w/combo of penicillin and aminoglycoside
Nosocomial (hospital-acquired) infections – transmission by hands & fomites (bed rails, instruments)
Virulence traits include biofilm formation and cytolysin production
Capable of genetic transfer via conjugative elements (transposons, plasmids) and bacteriophage, which may lead
to uptake of novel resistance genes (extrinsic resistance)
Most VRE are E. faecium; E. faecalis more common but less likely to be vanco resistant
o Use linezolid (bacterial protein synthesis inhibitor), daptomycin (bacteriocidal lipopeptide that inserts
into bacterial membrane and causes cytoplasmic leak), tigecycline (tetracycline derivative), and
dalfopristin-quinupristin (combo of inhibitors of bacterial protein synthesis); toxicity and emerging
resistance limit use