Streptococcus

Streptococcus is one of the two medically important genera of gram-positive cocci, the
other being Staphylococcus. Streptococci are identified as different species on blood agar
on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are
many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S.
pneumoniae, and the viridans streptococci (e.g., S. mutans, S. mitis, and S. sanguinis).
Streptococcal infections cause a wide array of clinical manifestations, including pharyngitis,
pneumonia, skin and soft tissue infections, endocarditis, septicemia, meningitis, and
streptococcal toxic shock syndrome. They are also responsible for the postinfectious
syndromes of acute rheumatic fever and poststreptococcal glomerulonephritis. Most
streptococci are sensitive to penicillin.

Last updated: October 5, 2022

CONTENTS

General Characteristics
Differentiation of Streptococcus Species
Pathogenesis
Diseases Caused by β-Hemolytic Streptococci
Diseases Caused by α-Hemolytic Streptococci
Identification and Prevention
References
General Characteristics

Shared characteristics
Gram-positive cocci: Some may lose positive staining after overnight incubation or if
the culture ages and bacteria die.
Grow in pairs or chains: Classic long chains are best seen when grown in liquid
medium.
Nonmotile
Non–spore-forming
Facultative anaerobes (oxygen tolerant)
Catalase negative:
Catalase is an enzyme that splits hydrogen peroxide into water and oxygen.
The state of being catalase negative is a key finding that differentiates
streptococci from staphylococci, which are catalase positive.
Habitats: skin and mucous membranes of humans and animals
Capsule
Important virulence factor
Encapsulated streptococci:
Hyaluronic acid: group A (S. pyogenes)
Polysaccharide:
Group B (S. agalactiae)
S. pneumoniae
Group D (Enterococcus)
Nonencapsulated streptococci:
Viridans streptococci
S. viridans is not a true or single species; rather, it is a pseudo-taxonomic
term.
Represents different groups of streptococci, including the S. bovis group
(e.g., S. gallolyticus), S. mitis, the S. mutans group, S. sanguinis, the S.
anginosus group, S. constellatus, S. intermedius, and the S. salivarius
group.
Nonencapsulated S. pneumoniae:
Some natural nonencapsulated phenotypes exist and cause disease.
Capsular production is lost by all encapsulated pneumococci after passing
through a few subcultures on agar, but they will again produce capsules
(and have enhanced virulence) if injected into mice.

Biofilm
Streptococci have the ability to form biofilms:
Densely packed bacterial communities
Grow on surfaces or human tissues
Bacteria secrete and surround themselves with a slimy matrix composed of polymers (
polysaccharides in streptococcal species).
Examples of biofilms:
Dental plaque
Bacterial colonization of chronic wounds
Significance:
More resistant to host immune defenses
 More resistant to antibiotics

Differentiation of Streptococcus Species

Gram-positive bacteria:
Most bacteria can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thick layer of peptidoglycan retain the crystal violet stain utilized in
 Gram staining but are not affected by the safranin counterstain. These bacteria appear as purple-blue
on the stain, indicating that they are gram positive. The bacteria can be further classified according to
morphology (branching filaments, bacilli, and cocci in clusters or chains) and their ability to grow in the
presence of oxygen (aerobic versus anaerobic). The cocci can also be further identified. Staphylococci
can be narrowed down on the basis of the presence of the enzyme coagulase and on their sensitivity to
the antibiotic novobiocin. Streptococci are grown on blood agar and classified on the basis of which
form of hemolysis they employ (α, β, or γ). Streptococci are further narrowed on the basis of their
response to the pyrrolidonyl-β-naphthylamide (PYR) test, their sensitivity to specific antimicrobials
(optochin and bacitracin), and their ability to grow on sodium chloride (NaCl) media.
Image by Lecturio. License: CC BY-NC-SA 4.0 (https://creativecommons.org/licenses/by-nc-sa/4.0/)

Serologic (Lancefield) classification

Groups A–V are identified on the basis of the antigens in the cell wall, pili, or capsule.
Now mostly of historic interest, as many more species have been described
Some streptococcal species are still traditionally referred to by their serologic types
(groups A, B, and D).
Group A: S. pyogenes
Group B: S. agalactiae
Group C: S. equisimilis, S. equi, S. zooepidemicus
Group D: Enterococcus faecalis, E. faecium, E. durans, S. bovis
Groups F, G, and L: S. anginosus
Group H: S. sanguis
Group K: S. salivarius
Group L: S. dysgalactiae
Groups M and O: S. mitis
Group N: Lactococcus lactis
Groups R and S: S. suis

Hemolytic classification
Streptococci grow well on blood agar. Streptococcus species are divided into 3 groups
on the basis of their hemolysis pattern:
β-Hemolytic: complete hemolysis (clear zone of hemolysis):
S. pyogenes
S. agalactiae
α-Hemolytic: partial hemolysis (green zone of hemolysis):
S. pneumoniae
Viridans streptococci (variable hemolytic patterns in some species)
γ-Hemolytic: no hemolysis:
S. gallolyticus (a member of the S. bovis group)
S. faecalis and S. faecium have been reclassified into the distinct genus of
Enterococcus as E. faecalis and E. faecium.
 Blood agar plate showing β-hemolytic colonies of S. pyogenes:
Note the complete (beta-type) hemolysis around each colony.
Image
(https://commons.wikimedia.org/wiki/File:Streptococcus_pyogenes_(Lancefield_Group_A)_on_Columbia_Horse_Blood_Agar_-
_Detail.jpg#/media/File:Streptococcus_pyogenes_(Lancefield_Group_A)_on_Columbia_Horse_Blood_Agar.jpg):
“Lancefield Group A” by Nathan Reading. License: CC BY 2.0 (https://creativecommons.org/licenses/by/2.0)

Distinguishing factors of the pathogenic streptococci

Distinguishing factors of the pathogenic streptococci

Species Morphology Usual habitat Distinguishing features

Species Morphology Usual habitat Distinguishing features

S. pyogenes (group Appear in Throat, skin Encapsulated by

A strep) pairs of hyaluronic acid
chains β-Hemolytic
Inhibited by
bacitracin
PYR positive

S. agalactiae (group Appear in Vagina, lower Encapsulated by

B strep) pairs or gastrointestinal polysaccharide
chains tract capsule
β-Hemolytic
Hippurate positive
cAMP test positive:
Increasing zone of
hemolysis when
plated with S. aureus
Bacitracin resistant

S. pneumoniae Lancet- Nasopharynx Encapsulated by

shaped polysaccharide
diplococci capsule
α-Hemolytic
Optochin sensitive
Bile soluble: cannot
grow in bile

Viridans Appear in Oral cavity, colon Nonencapsulated

streptococci: S. pairs or (S. bovis) α-Hemolytic
mutans, S. mitis, S. chains Optochin resistant
sanguinis Bile resistant: can
grow in bile
 Species Morphology Usual habitat Distinguishing features

Enterococci (formerly Appear in Mostly in intestine, Ɣ-Hemolytic

group D strep, pairs, short but oral cavity and (nonhemolytic)
reclassified as the chains, or vagina can be Grow in 6.5% NaCl
distinct genus singly colonized
Enterococcus): E.
faecalis, E. faecium
S. gallolyticus (in
group D and a
member of the S.
bovis group)

PYR: pyrrolidonyl-β-naphthylamide

Pathogenesis
Each pathogenic species of streptococci has key virulence factors that relate to their
spread and clinical manifestations. See the charts below for a summary of these
features in selected species:

Virulence factors and functions of S. pyogenes (group A strep)

Virulence factors Function

Capsule Inhibits phagocytosis

M protein (involved in rheumatic Antiphagocytic

fever) Molecular mimicry (
type II hypersensitivity reaction) of myosin in
heart valves: The mitral valve is affected most
often and the aortic valve less commonly.

Streptolysin O Lyses RBCs

 Virulence factors Function

Streptokinase (fibrinolysin) Converts plasminogen to plasmin and lyses blood

clots, allowing bacteria to escape from the clot

DNAse Depolymerizes DNA

Aids in spread by liquefying pus, which owes its
viscosity to DNA (mostly from dead neutrophils)

Hyaluronidase Aids in spread by splitting hyaluronic acid, an

important component of the ground substance of
connective tissue

Lipoteichoic acid (covers hairlike pili Adhere to epithelial cells

that project through capsule)

3 types of streptococcal pyrogenic SpeA and SpeC are called superantigens because
exotoxins: they stimulate T cells to produce cytokines by
SpeA: involved in scarlet fever binding to the V-beta region of the T-cell receptor.
and streptococcal In scarlet fever: Blood vessels are dilated
toxic shock syndrome because the cutaneous cytokine milieu is altered.
SpeB: protease, involved in In toxic shock syndrome: The overwhelming
poststreptococcal release of inflammatory cytokines by T cells
glomerulonephritis mediates shock.
(bacterial infection-related In poststreptococcal glomerulonephritis: Antigen
glomerulonephritis) –antibody complexes form on the glomerular
SpeC: involved in scarlet fever basement membrane. The two most important
and streptococcal group A strep antigens are SpeB and nephritis-
toxic shock syndrome associated plasmin receptor.

2 types of hemolysins: Lyse RBCs and also damage the membranes of

Streptolysin O: stimulates other cells
production of antibody anti–
streptolysin O (ASO); inactivated
by oxygen
Streptolysin S: not antigenic

Spe: Streptococcal pyrogenic exotoxins

Virulence factors and functions of S. agalactiae (group B strep)

 Virulence factors Function

Capsule Inhibits phagocytosis

Virulence factors and functions of S. pneumoniae

Virulence factors Function

Capsule Inhibits phagocytosis

IgA protease Mucosal invasion

Virulence factors and functions of S. mutans

Virulence factors Function

Dextrans Platelet adhesion

In vivo biofilm production Adhesion

Diseases Caused by β-Hemolytic Streptococci

Streptococcus pyogenes
Streptococcus pyogenes is the most virulent pathogen in the Streptococcus family.
Pharyngitis:
Most common infection caused by S. pyogenes
In infants and small children: subacute nasopharyngitis, palatal petechiae, cervical
lymphadenopathy; may lead to middle-ear infection
In older children and adults: intense nasopharyngitis, tonsillitis, purulent exudates, high
fever, cervical lymphadenopathy
 Asymptomatic infections: 20%
Many other etiologies of pharyngitis: adenovirus, infectious mononucleosis,
gonococcal infection, diphtheria

Streptococcal pharyngitis:
Redness and edema of the throat and palatal petechiae
Image (https://commons.wikimedia.org/wiki/File:Streptococcal_pharyngitis.jpg): “Streptococcal pharyngitis” by CDC/Dr.
Heinz F. Eichenwald. License: Public Domain (https://creativecommons.org/licenses/publicdomain/)

Skin and soft tissue infections:

Impetigo:
“Honey-crusted” skin lesions
Mostly affects children 2–5 years of age
Highly communicable, especially in hot, humid climates
May progress to cellulitis
May also be caused by Staphylococcus aureus
Erysipelas:
Infection of upper dermis and superficial lymphatics
Red, raised, rapidly advancing, and well-demarcated margin of infection (being
raised and well demarcated differentiates it from cellulitis)
Cellulitis:
Infection of deep dermis and subcutaneous fat
 Red, not raised, and not well-demarcated margin of infection (not being raised
and not being well demarcated differentiates it from erysipelas)
Abscess:
Localized collection of pus in a newly created cavity
S. pyogenes and Staphylococcus aureus (MRSA) are the most common causes of
abscesses on the trunk, extremities, axillae, or head and neck.
Necrotizing fasciitis (“flesh-eating bacteria” or “streptococcal gangrene”)
A necrotizing soft tissue infection [NSTI] that also includes necrotizing forms of
myositis and cellulitis
Fulminant tissue destruction, systemic signs of toxicity, and high mortality; usually
polymicrobial, with aerobic and anaerobic bacteria
Overlying skin may seem only mildly warm, with no clear portal of entry.
Predisposing factors: diabetes, trauma, immunosuppression
Pyrogenic exotoxins most likely contribute to shock via cytokines.
Surgical emergency: debridement and administration of antibiotics urgently
needed

Impetigo in a child:
The image shows characteristic “honey-crusted” lesions around the mouth.
Image (https://commons.wikimedia.org/wiki/File:OSC_Microbio_21_02_impetigo.jpg): “Microbio 21 02 impetigo” by CNX
OpenStax. License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/deed.en)

Puerperal fever: occurs when S. pyogenes enters uterus after delivery, causing
endometritis and bacteremia
Bacteremia or sepsis caused by:
Infected traumatic or surgical wounds
Skin infections (e.g., cellulitis)
Pharyngitis (rare)

Toxin-mediated diseases
Scarlet fever:
Usually in association with pharyngitis
Mediated by toxins (superantigen A or C)
Diffuse papular erythematous rash; palms, soles, and face usually spared
“Strawberry tongue”
Circumoral pallor

Rash of scarlet fever

 Image (https://en.wikipedia.org/wiki/Scarlet_fever#/media/File:Scarlet_fever_2.jpg): “The rash of scarlet fever” by Alicia
Williams. License: CC BY 2.5 (https://creativecommons.org/licenses/by/2.5)

Toxic shock syndrome (TSS):

Early-onset shock, bacteremia, respiratory failure, and multiorgan failure
Fatal in 30% of cases
May be preceded by minor trauma with local signs of infection
Mediated by superantigen toxins
Toxic shock syndrome can also be caused by Staphylococcus aureus, which can also
express superantigen toxins.

Postinfectious sequelae
Rheumatic fever:
2–3 weeks after pharyngitis
Early antibiotic treatment of pharyngitis decreases the incidence.
Associated with antibodies to streptolysin O, hyaluronidase, and streptokinase
♡
J NES criteria:
Joint involvement (polyarthritis)
♡(mitral valve stenosis, myocarditis, pericarditis)
Nodules (subcutaneous; on extensor surfaces)
Erythema marginatum (rash)
Sydenham's chorea (neurologic)

Poststreptococcal glomerulonephritis (PSGN):

Caused by specific nephritogenic strains that have the 2 most important antigens
(SpeB and nephritis-associated plasmin receptor)
Occurs 2–3 weeks after pharyngitis or impetigo
Deposition of immune complexes within glomerular basement membrane (type 3
hypersensitivity reaction)
Hematuria/proteinuria, edema, hypertension
Usually (but not always) benign and self-limited

Streptococcus agalactiae: The Group B Streptococci (GBS)

Frequently colonize genital (in 5%–30% of women) and GI tracts
In older adults with chronic medical conditions:
Most common infection: cellulitis
Sepsis
Less common: cystitis, pyelonephritis, pneumonia, septic arthritis, endocarditis,
meningitis
In pregnant women:
Urinary tract infection (or asymptomatic bacteriuria)
Chorioamnionitis
 Postpartum endometritis
In neonates:
Acquired in utero by ascending infection or during passage through vagina
Early (within 6 days) or late (up to 90 days) onset
Can present with:
Bacteremia (without focus)
Sepsis
Meningitis
Pneumonia
Respiratory distress syndrome

Diseases Caused by α-Hemolytic Streptococci

Streptococcus pneumoniae
Most common bacterial cause of community-acquired pneumonia
Presents with hypoxia, cough, tachypnea, tachycardia, fever
Human-to-human transmission by aerosols or close contact
Nasopharyngeal colonization is common (5%–40%). Aspiration of nasopharyngeal
secretions into the lungs can lead to pneumonia if:
Very large bacterial inoculum
Normal clearance mechanisms impaired by smoking, viral infections, alcohol or
drug intoxication, systemic illness, heart failure
Can also spread and cause bacteremia, which can result in bacterial seeding of other
organs:
CNS: meningitis, otitis media,
Cardiac: endocarditis, pericarditis
Rheumatic: septic arthritis, osteomyelitis
Infective endocarditis:
A bacterial vegetation (arrow) is seen on the tricuspid valve on an echocardiogram.
Image (https://commons.wikimedia.org/wiki/File:Endocarditis_ultrasound.JPG): “Endocarditis ultrasound” by Daisuke
Koya et al. License: CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/deed.en)

Viridans Streptococci
Most prevalent bacteria of the normal microbiota of the upper respiratory tract
Important for the healthy state of the mucous membranes
Most commonly get into the bloodstream through breaks in oral mucosa (e.g., during
dental procedures)
Have been associated with:
Sinusitis in immunocompromised patients
S. mutans: dental caries, endocarditis
S. mitis: endocarditis, bacteremia, high level of resistance to penicillin
S. bovis: endocarditis, biliary disease, common blood isolate in colon cancer
S. anginosus group: pyogenic infections in brain, liver, lung
S. salivarius group: bacteremia, endocarditis, meningitis

Enterococci
Reclassified into their own genus, Enterococcus
Very similar to Streptococcus in physical appearance and characteristics
Commensal organisms in human intestines
H b i t d ith
 Urinary tract infections
Diverticulitis
Spontaneous bacterial peritonitis
Endocarditis (commonly after manipulation of GI or urinary tract)
Meningitis (rare)

Identification and Prevention

Identification and prevention

Species Identification Prevention

S. pyogenes Gram stain (cannot Early (before day 8) antibiotic

Group A strep differentiate from a viridans treatment of pharyngitis to
(GAS) streptococcus) prevent rheumatic fever (RF) and
Rapid streptococcal antigen continued chemoprophylaxis for
test (“strep test”): specificity years in persons who have had
high, but sensitivity 77%–92% an attack of RF to prevent relapse
Throat culture: 24–48 hours of RF activity
Beta-hemolysis
PCR testing: not always
available
ASO titer, anti-DNAse titer: if
rheumatic fever or acute
poststreptococcal
glomerulonephritis
is suspected

S. agalactiae PCR-based tests on urine Screen all pregnant women at

group B strep ( Cultures: beta-hemolysis and 35–37 weeks for GBS and
GBS) biochemical testing administer IV antibiotics (penicillin
) during labor to prevent
neonatal infection
 Species Identification Prevention

S. pneumoniae Sputum Gram stain and Immunization, following U.S.

culture Advisory Committee on
Blood culture: alpha- Immunization Practices (ACIP)
hemolysis, then biochemical guidelines for different ages and
testing, molecular testing, or a medical conditions, with:
mass spectrometry method Pneumococcal conjugate
vaccine (Prevnar 13)
Pneumococcal polysaccharide
vaccine (Pneumovax 23)

Viridans Blood cultures, then Prophylactic antibiotics in patients

streptococci: S. biochemical testing (often with high-risk conditions (e.g.,
mutans, S. unreliable for viridans species, prosthetic heart valves,
bovis, S. mitis so molecular testing or a mass unrepaired cyanotic congenital
spectrometry method heart disease) who are
increasingly being used) undergoing a dental procedure

Enterococcus Cultures (growth in 6.5% NaCl),

then biochemical testing,
molecular testing, or mass
spectrometry methods

References
1. Group A Streptococcal Disease (GAS). Centers for Disease Control and Prevention
(https://www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html). Accessed December 27, 2020.
2. Haslam DB, St Gemelli JW (2018). Viridans Streptococci, Abiotrophia and Granulicatella Species, and
Streptococcus bovis Group (https://www.sciencedirect.com/science/article/pii/B9780323401814001213).
Retrieved December 27, 2020, from https://www.sciencedirect.com/topics/medicine-and-
dentistry/viridans-streptococci (https://www.sciencedirect.com/topics/medicine-and-dentistry/viridans-
streptococci)
3. Patterson MJ (1996). Streptococcus. Retrieved December 26, 2020, from
https://www.ncbi.nlm.nih.gov/books/NBK7611/ (https://www.ncbi.nlm.nih.gov/books/NBK7611/)
4. Puopolo KM, Baker CJ (2019). Group B streptococcal infection in neonates and young infants. Retrieved
December 26, 2020, from https://www.uptodate.com/contents/group-b-streptococcal-infection-in-
neonates-and-young-infants (https://www.uptodate.com/contents/group-b-streptococcal-infection-in-
 neonates-and-young-infants?
search=streptococcus&source=search_result&selectedTitle=7~150&usage_type=default&display_rank=6)
5. Stevens DL (2020). Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology,
clinical manifestations, and diagnosis. Retrieved December 26, 2020, from
https://www.uptodate.com/contents/invasive-group-a-streptococcal-infection-and-toxic-shock-syndrome-
epidemiology-clinical-manifestations-and-diagnosis (https://www.uptodate.com/contents/invasive-group-
a-streptococcal-infection-and-toxic-shock-syndrome-epidemiology-clinical-manifestations-and-diagnosis?
search=streptococcus%20pyogenes&source=search_result&selectedTitle=3~150&usage_type=default&d
isplay_rank=3)
6. Tuomanen EI (2019). Microbiology and pathogenesis of Streptococcus pneumoniae. Retrieved December
26, 2020, from https://www.uptodate.com/contents/microbiology-and-pathogenesis-of-streptococcus-
pneumoniae (https://www.uptodate.com/contents/microbiology-and-pathogenesis-of-streptococcus-
pneumoniae?
search=streptococcus%20pneumoniae&source=search_result&selectedTitle=4~150&usage_type=default
&display_rank=3)
7. Wald ER (2020). Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical features
and diagnosis. Retrieved 26 December 2020, from https://www.uptodate.com/contents/group-a-
streptococcal-tonsillopharyngitis-in-children-and-adolescents-clinical-features-and-diagnosis
(https://www.uptodate.com/contents/group-a-streptococcal-tonsillopharyngitis-in-children-and-
adolescents-clinical-features-and-diagnosis?
search=streptococcus&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=2)
8. Martin CS, Bradshaw JL, Pipkins HR, McDaniel LS (2018). Pulmonary disease associated with
nonencapsulated streptococcus pneumoniae. Open Forum Infectious Diseases. 2018;5(7).
https://doi.org/10.1093/ofid/ofy135 (https://doi.org/10.1093/ofid/ofy135)
9. Riedel S, Hobden JA (2019). In Riedel, S, Morse, S.A., Mietzner, T., Miller, S. (Eds.), Jawetz, Melnick, &
Adelberg’s Medical Microbiology (28th ed., pp. 215-233).
10. Advisory Committee on Immunization Practices (ACIP). CDC. (2020, December 22).
https://www.cdc.gov/vaccines/acip/index.html (https://www.cdc.gov/vaccines/acip/index.html)