Species of streptococci are classified based on theirhemolytic properties.[10] Alpha-hemolytic species cause oxidization of iron inhemoglobin molecules within red blood cells, giving it a greenish color on blood agar.Beta-hemolytic species cause complete rupture of red blood cells. On blood agar, this appears as wide areas clear of blood cells surrounding bacterial colonies.Gamma-hemolytic species cause no hemolysis.[11]
Beta-hemolytic streptococci are further classified byLancefield grouping, aserotype classification (that is, describing specific carbohydrates present on the bacterial cell wall).[6] The 21 described serotypes are named Lancefield groups A to W (excluding E, I and J). This system of classification was developed byRebecca Lancefield, a scientist atRockefeller University.[12]
In the medical setting, the most important groups are the alpha-hemolytic streptococciS. pneumoniae andStreptococcusviridansgroups, and the beta-hemolytic streptococci of Lancefield groups A and B (also known as "group A strep" and "group B strep").
Whenalpha-hemolysis (α-hemolysis) is present, a blood based agar under the colony will appear dark and greenish due to the conversion of hemoglobin to greenbiliverdin.Streptococcus pneumoniae and a group of oral streptococci (Streptococcus viridans or viridans streptococci) display alpha-hemolysis.Alpha-hemolysis is also termed incomplete hemolysis or partial hemolysis because the cell membranes of the red blood cells are left intact. This is also sometimes called green hemolysis because of the color change in the agar.[citation needed]
S. pneumoniae (sometimes called pneumococcus), is a leading cause of bacterialpneumonia and the occasional etiology ofotitis media,sinusitis,meningitis, andperitonitis. Inflammation is thought to be the major cause of how pneumococci cause disease, hence the tendency of diagnoses associated with them to involve inflammation. They possess no Lancefield antigens.[2]
Theviridans streptococci are a large group ofcommensal bacteria that are eitheralpha-hemolytic, producing a green coloration on bloodagar plates (hence the name "viridans", from Latinvĭrĭdis, green), or nonhemolytic. They possess no Lancefield antigens.[2]
Beta-hemolysis (β-hemolysis), sometimes called completehemolysis, is a complete lysis of red cells in the media around and under the colonies: the area appears lightened (yellow) and transparent. Streptolysin, an exotoxin, is the enzyme produced by the bacteria which causes the complete lysis of red blood cells. There are two types of streptolysin: Streptolysin O (SLO) and streptolysin S (SLS). Streptolysin O is an oxygen-sensitive cytotoxin, secreted by most group AStreptococcus (GAS), and interacts with cholesterol in the membrane of eukaryotic cells (mainly red and white blood cells, macrophages, and platelets), and usually results in beta-hemolysis under the surface of blood agar. Streptolysin S is an oxygen-stable cytotoxin also produced by most GAS strains which results in clearing on the surface of blood agar. SLS affects immune cells, including polymorphonuclear leukocytes and lymphocytes, and is thought to prevent the host immune system from clearing infection.Streptococcus pyogenes, or GAS, displays beta hemolysis.
Some weakly beta-hemolytic species cause intense hemolysis when grown together with a strain ofStaphylococcus. This is called theCAMP test.Streptococcus agalactiae displays this property.Clostridium perfringens can be identified presumptively with this test.Listeria monocytogenes is also positive on sheep's blood agar.
The invasive infections caused by group A beta-hemolytic streptococci tend to be more severe and less common. This occurs when the bacterium is able to infect areas where it is not usually found, such as theblood andorgans.[14] The diseases that may be caused include streptococcaltoxic shock syndrome,necrotizing fasciitis,pneumonia, andbacteremia.[13] Globally, GAS has been estimated to cause more than 500,000 deaths every year, making it one of the world's leadingpathogens.[13]
S. agalactiae, or group Bstreptococcus,GBS, causes pneumonia and meningitis innewborns and theelderly, with occasional systemicbacteremia. Importantly,Streptococcus agalactiae is the most common cause of meningitis ininfants from one month to three months old. They can also colonize the intestines and the female reproductive tract, increasing the risk for prematurerupture of membranes during pregnancy, andtransmission of the organism to the infant. TheAmerican College of Obstetricians and Gynecologists,American Academy of Pediatrics, and theCenters for Disease Control recommend all pregnant women between 35 and 37 weeks gestation to be tested for GBS. Women who test positive should be given prophylactic antibiotics during labor, which will usually prevent transmission to the infant.[15] Group III polysaccharide vaccines have been proven effective in preventing the passing of GBS from mother to infant.[16]
The United Kingdom has chosen to adopt a risk factor-based protocol, rather than the culture-based protocol followed in the US.[17] Current guidelines state that if one or more of the following risk factors is present, then the woman should be treated withintrapartum antibiotics:
This protocol results in the administration of intrapartum antibiotics to 15–20% of pregnant women and the prevention of 65–70% of cases of early onset GBS sepsis.[18]
Many former group D streptococci have been reclassified and placed in the genusEnterococcus (includingE. faecalis,E. faecium,E. durans, andE. avium).[22] For example,Streptococcus faecalis is nowEnterococcus faecalis.E. faecalis is sometimes alpha-hemolytic andE. faecium is sometimes beta hemolytic.[23]
Nonhemolytic streptococci rarely cause illness. However, weakly hemolytic group D beta-hemolytic streptococci andListeria monocytogenes (which is actually agram-positive bacillus) should not be confused with nonhemolytic streptococci.
Group F streptococci were first described in 1934 by Long andBliss among the "minute haemolytic streptococci".[24] They are also known asStreptococcus anginosus (according to the Lancefield classification system) or as members of theS. milleri group (according to the European system).
These streptococci are usually, but not exclusively, beta-hemolytic.Streptococcus dysgalactiae subsp. canis[20] is the predominant subspecies encountered. It is a particularly common GGS in humans, although it is typically found on animals.S. phocae is a GGS subspecies that has been found in marine mammals and marine fish species. In marine mammals it has been mainly associated withmeningoencephalitis,sepsis, andendocarditis, but is also associated with many other pathologies. Its environmental reservoir and means of transmission in marine mammals is not well characterized. Group G streptococci are also considered zoonotic pathogens.
Group H streptococci cause infections in medium-sized canines. Group H streptococci rarely cause human illness unless a human has direct contact with the mouth of a canine. One of the most common ways this can be spread is human-to-canine, mouth-to-mouth contact. However, the canine may lick the human's hand and infection can be spread, as well.[25]
Example of a workup algorithm of possible bacterial infection in cases with no specifically requested targets (non-bacteria, mycobacteria etc.), with most common situations and agents seen in a New England setting. MainStreptococcus groups are included as "Strep." at bottom left.
In clinical practice, the most common groups ofStreptococcus can be distinguished by simple bench tests, such as the PYR test forgroup A streptococcus. There are also latex agglutination kits which can distinguish each of the main groups seen in clinical practice.
Streptococcal infections can be treated with antibiotics from thepenicillin family. Most commonly, penicillin or amoxicillin is used to treat strep infection. These antibiotics work by disrupting peptidoglycan production in the cell wall.[26] Treatment most often occurs as a 10-day oral antibiotic cycle. For patients with penicillin allergies and those suffering from skin infections, clindamycin can be used. Clindamycin works by disrupting protein synthesis within the cell.
Phylogenetic tree ofStreptococcus species, based on data from PATRIC.[27] 16S groups are indicated by brackets and their key members are highlighted in red.
Streptococci have been divided into six groups on the basis of their16S rDNA sequences:S. anginosus, S. gallolyticus, S. mitis, S. mutans, S. pyogenes andS. salivarius.[28] The 16S groups have been confirmed by whole genome sequencing (see figure). The important pathogensS. pneumoniae andS. pyogenes belong to theS. mitis andS. pyogenes groups, respectively,[29] while the causative agent ofdental caries,Streptococcus mutans, is basal to theStreptococcus group.
A conceptual diagram ofStreptococcus subclade taxonomy based on phylogenetic trees and theconserved signature indels (CSIs) that are specifically shared by groups of streptococci.[30] The number of CSIs identified for each group is shown.
Recent technological advances have resulted in an increase of available genome sequences forStreptococcus species, allowing for more robust and reliable phylogenetic and comparative genomic analyses to be conducted.[30] In 2018, the evolutionary relationships withinStreptococcus was re-examined by Patel and Gupta through the analysis of comprehensivephylogenetic trees constructed based on four different datasets of proteins and the identification of 134 highly specific molecular signatures (in the form ofconserved signature indels) that are exclusively shared by the entire genus or its distinct subclades.[30]
The results revealed the presence of two main clades at the highest level withinStreptococcus, termed the "Mitis-Suis" and "Pyogenes-Equinus-Mutans" clades.[30] The "Mitis-Suis" main clade comprises the Suis subclade and the Mitis clade, which encompasses the Angiosus, Pneumoniae, Gordonii and Parasanguinis subclades. The second main clade, the "Pyogenes-Equinus-Mutans", includes the Pyogenes, Mutans, Salivarius, Equinus, Sobrinus, Halotolerans, Porci, Entericus and Orisratti subclades. In total, 14 distinct subclades have been identified within the genusStreptococcus, each supported by reliable branching patterns in phylogenetic trees and by the presence of multipleconserved signature indels in different proteins that are distinctive characteristics of the members of these 14 clades.[30] A summary diagram showing the overall relationships among theStreptococcus based on these studies is depicted in a figure on this page.
The genomes of hundreds of species have been sequenced.[32] MostStreptococcus genomes are 1.8 to 2.3 Mb in size and encode 1,700 to 2,300 proteins. Some important genomes are listed in the table.[33] The four species shown in the table (S. pyogenes, S. agalactiae, S. pneumoniae, andS. mutans) have an average pairwise protein sequence identity of about 70%.[33]
Bacteriophages have been described for many species ofStreptococcus. 18prophages have been described inS. pneumoniae that range in size from 38 to 41 kb in size, encoding from 42 to 66 genes each.[34] Some of the firstStreptococcus phages discovered were Dp-1[35][36]and ω1 (alias ω-1).[37][38][39]In 1981 the Cp (Complutense phage 1, officiallyStreptococcus virus Cp1,Picovirinae) family was discovered with Cp-1 as its first member.[40] Dp-1 and Cp-1 infect bothS. pneumoniae andS. mitis.[41] However, the host ranges of mostStreptococcus phages have not been investigated systematically.
Natural genetic transformation involves the transfer of DNA from one bacterium to another through the surrounding medium. Transformation is a complex process dependent on the expression of numerous genes. To be capable of transformation a bacterium must enter a special physiologic state referred to ascompetence.S. pneumoniae,S. mitis andS. oralis can become competent, and as a result actively acquire homologous DNA for transformation by a predatory fratricidal mechanism[42] This fratricidal mechanism mainly exploits non-competent siblings present in the same niche[43] Among highly competent isolates ofS. pneumoniae, Li et al.[44] showed that nasal colonization fitness and virulence (lung infectivity) depend on an intact competence system. Competence may allow the streptococcal pathogen to use external homologous DNA for recombinational repair of DNA damages caused by the host's oxidative attack.[45]
^abPatterson MJ (1996). Baron S; et al. (eds.).Streptococcus.In: Baron's Medical Microbiology (4th ed.). Univ of Texas Medical Branch.ISBN978-0-9631172-1-2.(via NCBI Bookshelf).
^Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A (August 2002). "Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC".MMWR. Recommendations and Reports.51 (RR-11):1–22.PMID12211284.
^abHaslam DB, St Geme III JW (2023). "122 - Groups C and G Streptococci". In Long SS, Prober CG, Fischer M, Kimberlin D (eds.).Principles and Practice of Pediatric Infectious Diseases (Sixth ed.). Elsevier. pp. 752–753.doi:10.1016/B978-0-323-75608-2.00122-1.ISBN978-0-323-75608-2. Note that according to the same source, the subspeciesequisimilis is a grouping of largeS. dysgalactiae colonies, whether they are members of Group C or Group G.
^Köhler W (June 2007). "The present state of species within the genera Streptococcus and Enterococcus".International Journal of Medical Microbiology.297 (3):133–150.doi:10.1016/j.ijmm.2006.11.008.PMID17400023.
^Holt et al. (1994).Bergey's Manual of Determinative Bacteriology (9th ed.). Lippincott Williams & Wilkins.ISBN0-683-00603-7
^"Streptococcus".PATRIC. Blacksburg, VA: Virginia Bioinformatics Institute. Archived fromthe original on 2013-03-10.
^abFerretti JJ, Ajdic D, McShan WM (May 2004). "Comparative genomics of streptococcal species".The Indian Journal of Medical Research.119 (Suppl):1–6.PMID15232152.
^McShan, W. Michael; Nguyen, Scott V. (2016), Ferretti, Joseph J.; Stevens, Dennis L.; Fischetti, Vincent A. (eds.),"The Bacteriophages of Streptococcus pyogenes",Streptococcus pyogenes: Basic Biology to Clinical Manifestations, Oklahoma City (OK): University of Oklahoma Health Sciences Center,PMID26866212, retrieved2024-02-07
^McDonnell M, Ronda C, Tomasz A (1975). ""Diplophage": a bacteriophage of Diplococcus pneumoniae".Virology.63:577–582.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^López R (September 2004). "Streptococcus pneumoniae and its bacteriophages: one long argument".International Microbiology.7 (3):163–171.PMID15492930.PDF via web archive (9 Aug 2017)
