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Micro Chapter 12: Streptococci and Enterococci: “Strep Throat” and Beyond
Streptococci and enterococci can cause strep pharyngitis (“strep throat”), cellulitis, neonatal meningitis,
brain abscess, endocarditis, and life-threatening necrotizing fasciitis (“flesh-eating” bacteria)
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Strep pyogenes is aka group A strep, and cause the most widespread disease in humans
Pneumococcus aka strep pneumonia
Strep look like a “string of pearls”
Three ways to classify strep and enterococci:
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Their hemolytic pattern – when strep and enterococci ar grown on blood agar media, the
colonies may be surrounded by an area of partial hemolysis that looks green (α-hemolysis), an
area of complete hemolysis that looks clear (β-hemolysis), or there’s no zone (γ or
nonhemolysis) – page 162 – pic of hemolytic classification
Lancefield classification – groups them by their cell wall antigens, into groups A-U
Species
Enterococci interact with group D antisera (serum with antibodies in it), but are considered a separate
genus
Group A strep aka S. pyogenes are the more important pathogen to humans from the strep family
We’ve decreased how common S. pyogenes infections are in the developed world
S. pyogenes-caused disease is most common in school aged children, and primarily presents as acute
pharyngitis (“strep throat”)
The other common site of infection is the skin and soft tissues, causing infections called pyoderma
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Pyoderma is seen more in children and more often in hot humid weather
Group A strep is usually not associated with any GI infections
S. pyogenes is usually found in the nasopharynx and on the skin of humans
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Up to 1/5 of kids may carry group A strep for weeks at a time in their pharynx during the winter,
but most won’t have any symptoms
Person-person spread of strep is mediated by respiratory droplets or by direct contact for skin
transmission
S. pyogenes (group A strep) is β-hemolytic and gram-positive, and grows in chains or pairs
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Group A strep ferments carbons to make lactic acid
Page 162 – table on the classification and disease caused by each strep species
Group A strep entry:
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For strep pyoderma infections – the bacteria must enter deeper layers of skin through direct
implantation after a break or trauma, since group A strep can’t penetrate intact skin
For strep pharyngeal infections – the bacteria binds to mucous membranes of the pharynx using
adhesins, which keep the bacteria from being swept away by fluid secretions
o M protein is an important adhesin to keratinocytes, which are the main cell type in the
outer layer of the skin
o The strep hyaluronic acid capsule may allow group A strep to bind the host hyaluronic
acid recptor CD44 found on the surface of pharyngeal epithelial cells and skin
keratinocytes
o Group A strep also adhere to host ECM stuff like fibronectin and laminin, using ECM
adhesins, lipoteichoic acid, strep fibronectin-binding proteins, and serum opacity factor
Once group A strep enters the host, it must evade phagocytosis and the immune response to
multiply and establish an effective infection
o The M protein and HA capsule again help, this time to evade phagocytosis
o Group A strep can also make proteins that degrade the chemotaxins that recruit
neutrophils to the infection site, inactivate or degrade antibodies, and block
antimicrobials
Spread and multiplication of group A strep:
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Group A strep usually stays localized to the site of initial infection
In the oropharynx, group A strep infections are usually self-limiting and localized to the pharynx
and tonsils, causing erythema and exudate
Benign group A strep infections of the superficial layers of the skin cause crusty honey-colored
lesions called impetigo
o Impetigo is most common in children living in hot, humid climates
Group A infections in deeper layers of skin cause erysipelas and cellulitis
Rarely, group A strep can reach the fascial planes between the skin and muscle, usually from a
breach through the skin (like a bug bite)
o In these cases infection may spread rapidly from the initial site of infection
Group A strep release several enzymes that may promote spread along tissue planes, causing
life-threatening diseases like necrotizing fasciitis and myositis
o Includes proteases, hyaluronidase, deoxyribonucleases (DNases), and streptokinase
o Streptokinase can bind to human plasminogen to convert it to plasmin, and the
plasmin then binds to the group A strep surface
 Plasmin-coated group A strep can degrade and spread through fibrin, which is a
major part of blood clots that act as a barrier to microbial spread
o Group A strep can also secrete streptolysins S and O, which are hemolysins that lyse the
membranes of host cells
 These hemolysins lyse RBCs, which is the reason why group A strep is β
hemolytic on blood agar
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M protein is a big part of how group A strep causes problems
o M protein is a surface protein that attaches to the cell wall of the pathogen
o M protein works in adhering to keratinocytes
o M protein can also prevent opsonization by complement in two ways:
 First, M protein binds the host cell fibrinogen, which interferes with the
alternative pathway of complement by forming a dense layer on the bacterial
surface
 Second, M protein binds host complement control proteins to inhibit
opsonization
o Despite the ways to fight opsonization, our antibodies still usually win out and opsonize
M proteins
o The problem is that there are so many different types of M proteins, that we often don’t
have antibodies built up to them
The hyaluronic acid capsule is another antiphagocyte structure on the strep surface
o There’s lots of HA in human connective tissue
o So the strep surround themselves with an HA capsule antigen to camouflage
themselves, and not trigger an immune response
o The HA capsule though limits the streps ability to bind epithelial cells
Damage caused by group A strep:
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Group A strep characteristically evokes an intense inflammatory response in tissues, that hurts
the host tissues
The digestive enzymes group A strep uses also do a lot of damage
The group A strep can go into blood and release toxins, called septicemia, or the toxins alone
can go into blood, called toxemia
Scarlet fever – toxemia caused by pharyngeal infections
o Characterized by pharyngeal infection and rash somewhere distal in the body
o The three toxins that casue scarlett fever are strep pyrogenic exotoxins (SPE) A, B, and C
o SPE-A and SPE-C are also bacterial superantigens that can activate lots of T cells, causing
mass release of proinflammatory cytokines, which leads to shock and multiorgan failure
 Called strep toxic shock syndrome (STSS)
o Most group A strep infections are mild, self-limited diseases
 But the intense inflammatory rxn to the infection may cause a group of diseases
called the nonsuppurative sequelae (means nonpus forming secondary
manifestations)
o The most feared sequelae of group A strep is acute rheumatic fever, which causes valve
heart disease
 Pharyngitis is the only kind of strep that can cause acute rheumatic fever (ARF)
 The symptoms of acute rheumatic fever are called Jones criteria:
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Carditis, polyarthritis, chorea (neuro problem with uncontrollable
dance like movements), skin nodules, and a rash called erythema
maginatum
 The most common are carditis and polyarthritis, and eventually all
these acute manifestations will resolve
 The main reason you treat strep pharyngitis with antibiotics is to prevent
acute rheumatic fever and heart problems
 The ongoing inflammation in the heart can lead to lots of mitral and/or aortic
valve scarring and stenosis, called rheumatic heart disease, leading to heart
failure
 The turbulent flow of blood across a scarred or deformed valve can predispose
to bacterial endocarditis
 Treatment of strep within 9 days can prevent acute rheumatic fever, by
preventing a full immune response to be mounted
 People who develop acute rheumatic fever have to take prophylactic antibiotics
well into adulthood or for life to prevent another strep infection that would
worsen the heart damage
 Group A strep has several stuff that look similar to host stuff to the immune
system, so acute rheumatic fever may be an autoimmune disease
 Group A strep M proteins cross-react with host tissue like this
 Strains of group A strep that are more likely to cause acute rheumatic fever are
called M-strains, but even so only a minority of people with these strains
develop ARF
The other important nonsuppurative sequel of group A strep infection is acute
poststrep glomerulonephritis (APSGN)
 Only a few M-types cause glomerulnephritis
 APSGN can follow both pharyngitis and pyodermal infections
 Antibiotics don’t effect whether APSGN will happen
 Antigen-antibody complexes are made and deposited in the glomerulus to cause
kidney injury
 Shows up 1-4 weeks after infection
 People with APSGN have blood and increased protein in their urine
Both acute rheumatic fever and APSGN can persist after the infection leaves the body
Diagnosis of gropu A strep:
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Impetigo – infection of the most superficial skin layers, that looks like a cluster of small blisters
on a pink base that breaks down to honey colored crusts
Erysipelas – raised bright red patch of skin with a sharply demarked and rapidly advancing
margin
Deep infections like myositis and necrotizing fasciitis are accompanied by excruciating pain and
often evidence of overlying skin necrosis
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Strep pharyngitis is very hard to tell apart from common viral pharyngtitis
o Often use a rapid strep test on a throat swab
 Very specific, so positive = strep pharyngitis
 It looks for group A carb antigens
 Not sensitive though compared to throat cultures, so you can’t rule out strep
pharyngitis until you get a negative throat culture
Treatment of group A strep:
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Group A strep is not resistant to penicillin, so penicillin is drug of choice for those not allergic
o Erythromycin or other macrolides can be used for allergy (50S)
Group B strep (GBS, strep agalactiae) – aerobic gram positive diplococcic that are β hemolytic
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Group B strep are common inhabitants of the lower GI and female genital tracts
Group B strep usually don’t cause significant disease in healthy people
Group B strep gotten by a newborn can be life-threatening if the baby gets it in the vagina
during delivery
o Up to half of pregnant women are colonized, so pregnant women are screened for
group B strep
o If positive, mom is given intrapartum antibiotics to reduce risk of transmission
o Group B strep is a leading cause of neonatal sepsis and meningitis, and those that
survive often live with seizures, deafness, developmental delay, and motor defecits
Elderly are also susceptible to group B strep
Luckily, group B strep is also still susceptible to penicillin for first line therapy
Like group A, group B strep evade opsonization and phagocytosis by the polysaccharide capsule
o These polysaccharides are poor antigens for stimulating host immune resonpse
Group C and G strep (S. dysgalactiae) – β hemolytic and cause problems similar to group A
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Cause respiratory and deep tissue infections, and the kidney toxicity
Also use M proteins, adhesins, and streptokinase
Strep viridans – α hemolytic in the oral cavity, that cause green discoloration on agar
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S. mutans and S. sobrinus are in dental plaque, that makes lactic acid during metabolism of
sugars, causing dental caries
Most strep viridans can also get into blood and cause endocarditis
Enterococci – gram positive cocci that grow in chains or pairs and ferment carbon to make lactic acid,
and can grow in bile and high salt
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originally called group D strep, but then were reclassified as their own genus
E. faecalis and E. faecium cause UTIs, wound infections, endocarditis, abdominal abscesses
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Enterococci are part of the normal flora of the GI and GU, and are different from strep in that
they resist bile and high salt found in the intestine
Enterococci became one of the most feared nosocomical (hospital-acquired) infections because
they have become resistance to every antibiotic against gram-positive bacteria
o They have tons of intrinsic resistance to antibiotics
o Penicillin usually kills bacteria by inhibiting cell wall making, but in enterococci
penicillin is only bacteriostatic (stops growth)
o Enterococci also resist aminoglycoside entry
o You can still kill enterococci, by combining penicillin and aminoglycosides, since
penicillin weakens the wall enough to let aminoglycosides in and stop protein synthesis
o But then enterococci can do genetic transformation with transposons and plasmids to
develop extrinsic resistance
o Vancomycin-resistant enterococci (VRE) spread through plasmids and transposons, and
this is how we got MRSA in staph aureus
 Most VRE are E. faecium
 E. facialis is less likely to be VRE
o Linezolid and daptomycin were developed to treat VRE
Enterococci can be spread by the hands of health care workers, and inaminate objects
Enterococci have low virulence, but do form biofilm and cytolysin