Group a Streptococcus
From MicrobeWiki, the student-edited microbiology resource
A Microbial Biorealm page on the genus Group a Streptococcus
Contents |
Classification
Higher order taxa
Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae; Streptococcus
Species
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NCBI: Taxonomy |
Group A Streptococcus
Description and significance
Streptocci are a very large group of gram positive cocci, spherical, bacteria that grow in chains or pairs. Group A Streptococcus (GAS) bacteria do not form spores, are nonmotile, and aggregate themselves in chains. Streptococcus are found primarily on the skin and in the upper respiratory tract of humans. Some colonies of GAS bacteria produce large amounts of hyaluronic acid, which often appears as mucus. Streptococci are spherical in shape, usually range from 0.6-1 µm in diameter and produce colonies of about 1 mm in diameter.
Edited by Braeden Carrico, a student of Rachel Larsen @ UCSD.
Genome structure
Streptococcus pyogenes, a common GAS bacterium, has a genome of 1,852,442 base pairs and a GC content of 38.5%.(Ferretti) Of all these base pairs, over 40 of the genes encoded in its genome are virulence genes, genes which make people sick. A 37.4 kb foreign genetic element, identified as (RD2), which is similar in gene content and organization to genomic islands found in group B streptococci (GBS), the major cause of neonatal infections, was found in a Serotype M28 strain of GAS.(Zhang) RD2 encodes 7 genes, 6 of which have not been identified. One gene, Spy1325, is "very well conserved in GAS strains of distinct M protein serotypes."(Zhang) Mice that have been immunized against Spy1325 showed increased survival rates when infected with GAS bacteria containing the spy1325 gene.
One reason for Streptococcus's ability to evade its host's defense mechanisms is that Streptococcus's protein coats, particulary Streptococcus pyogenes's, undergo "Molecular Mimicry." Molecular mimicry is when the protein coat of an invader alters itself in a way that the host's defense systems mistakes it for one of its own. This is very important because its ability to evade our systems of defense and not elicit an immune response means that it is free to divide and infect other tissues uninhibited by our body's defensive mechanisms. (Tsuchiya)
Cell structure and metabolism
Structure
Group A streptococcus are non-motile bacteria, so direct contact with saliva or nasal discharge of an infected person is require in order for the bacteria to spread among people. It is rarer, though no unheard of, to contract group A streptoccus through casual contact with an infected person. Population density seems to be the major factor here. The more heavily populated an area is, the more likely a person is to contract group A streptococcus if they come in contact with an infected person.
Metabolism
Most Streptococci are facultative anaerobes, although some are obligate anaerobes. They usually require a complex culture medium in order to grow. (Ferretti) Since they are found in the upper respiratory tract and on the skin, most have to be facultative anaerobes.
Ecology
Traditionally, vaccines target extracellular proteins on the bacterium being targeted. Recently, several new proteins were discovered that protect mice against,"... lethal intranasal challenge with virulent group A Streptococcus."(Musser) Although this work is very preliminary, it shows a lot of potential because GAS bacteria are the leading cause of preventable childhood heart disease globally because of their ability to cause rheumatic heart disease and rheumatic fever. (Musser) These researchers used a technique called reverse vaccinology, which, put simply, is the process in which they clone as many proteins as possible, over express them, and inject recombinant proteins into animals and see what responses they elicit.(Musser) Out of all the proteins identified through over expression and animal injection, they discovered 2 proteins that produce immunity against strain DSM2071. This is very encouraging news because with a more time and research, a vaccine could be created to fight these very deadly childhood diseases.
Pathology
Group A streptococcus are human specialized bacteria. Group A Streptococci tend to live in the upper respiratory tract of humans and on the skin. On rare occasions, they are found in the lower respiratory tracts, which usually results in pneumoniae, which is a result of Streptococcus pneumoniae residing in the lower respiratory tract.(Sharma) The main virulence factor associated with Group A Streptococcus, GAS, is the M protein. The M protein helps the bacterium to resist phagocytosis, which in turn encourages rapid cell division. The M protein is also associated with the initiation of diseases in humans. The M protein spans the cell membrane and has special adherins that help it adhere to the host cell, thus resisting phagocytosis.(Sharma)
Some signs of a Group A streptococcus infection are: Fever, sore throat, swollen lymph glands, and red weeping skin sores. Early signs of necrotizing fasciitis, commonly known as "flesh eating bacteria," are severe pain and swelling around the wound and fever. Symptoms usually appear about 1-3 days after infection.
Neutrophils, the primary defensive system against invading organisms, are vital in the maintnance and protection of the human body. One way GAS bacteria penetrate the human defense system is that they inhibit/ inactivate neutrophils. Neutrophils are a type of white blood cell, which are the initial defense mechanisms of the body. Neutrophils produce reactive oxygen species, (ROS), that normally destroy foreign organisms that have become engulfed due to the process of phagocytosis. However, since GAS strains can often resist phagocytosis through their M proteins, neutrophils do not recognize them and as a result, they are not destroyed.(Ovanka)
One way that GAS strains evade the host’s defense mechanisms is to inactivate/ inhibit phagocytosis. Neutrophils “are essential effector cells of the human innate immune system and provide the primary defense against invading microorganisms.”(Ovanka) They produce reactive oxygen species and antibacterial granules to degrade the bacteria engulfed by phagocytosis. These are normally very effective ways to destroy the bacteria, but it has been found that some GAS strains have become resistant to the antibacterial granules and ROS produced by the host's defense systems. Very little is known how bacteria actually recognize and neutralize the hosts defense mechanisms, but there is evidence that a 2 gene regulatory system and the ability to adhere to the mucus membranes plays a major role. Ihk-Irr, two genes found in GAS strains, are believed to be responsible for expressing a large part of the pathogenic part of the bacterial genome. Experiments done on mice showed that inactivation of these two genes led to a very high rate of bacterial cell death when compared to the Ihk-Irr wild types. Another way GAS strains are believed to resist phagocytosis is by adhering to mucus membranes with lipoteichoic acid (LTA), for reasons that are not understood.(Ovanka)Another reason why Group A streptococcus can be very virulent and elusive is because of their ability to horizontally transmit genes among other GAS strains. Competence plays a major role in creating diversity and increasing the size of their genomes. The prophages acquired through transformation can add genes that express both virulence and characteristics that improve the bacterium's chances of survival.(Sharma)
Application to Biotechnology
In the ongoing bacterium battle, Streptococcus are known to use hydrogen peroxide to kill competing bacterium. This was discovered by a catalase test. Catalase, an enzyme that degrades hydrogen peroxide into water and oxygen, was introduced into a medium containing Streptococcus pneumoniae,(GAS), and Staphylococcus aureus. When this occurred, S. aureus was not killed, like it usually was when in contact with S. pneumoniae. This allowed them to conclude that S. pneumoniae used hydrogen peroxide during bactericidal activity.(Regev-Yochay) Hydrogen peroxide, a reactive oxygen species, is also toxic to human cells, so finding a way to control S. pneumoniae's ability to secrete hydrogen peroxide is very useful in modern medicine.(Regev-Yochay)
Current Research
Research is currently being conducted to find new antibiotics to combat antibiotic resistant strains of bacteria. Pathogenic streptococci were treated with pyridine based nucleoside analogs, which were successful in killing the bacteria. Certain nucleoside analogs, "3'-azido-3'-deoxy-thymidine (AZT) and 2',2'-difluoro-2'deoxycytidine gemcitabine, were activated by the bacteria's own deoxyribonucleoside kinases"(Sandrini), which led to bacterial cell death. This is promising for the development of new antibiotics, which is quickly becoming a major health crisis.(Sandrini)
Research has been conducted on the effects of oleanolic acid, an extract from Salvia officinalis, on VRE bacteria, vancomycin resistant enterococci. Ursolic acid was also tested. They found out that both compounds had "antimicrobial" activity, meaning they were effective against VRE bacterium. These were also effective against Streptococcus pneumoniae and methicillin resistant Staphylococcus aureus. The doses varied slightly, but generally 8 mug/ml of oleanolic acid and 4 mug/ml of Ursolic acid were needed in order to be effective.(Horiuchi)
The most promising research being conducted on GAS bacteria is in the development of a vaccine. A research paper titled, "Progress in M-protein-based subunit vaccines to prevent rheumatic fever and rheumatic heart disease," describes how a vaccine is being created that will target the M-protein on GAS bacteria. As mentioned above, the M-protein is the main virulence causing factor of the GAS strains. Some medical professionals are concerned that if a vaccine is developed which targets the M-protein, "autoimmunity" could result. They are worried about this potential resistance to the vaccine because GAS bacteria can perform "molecular mimicry," meaning that they can change their protein coats in such a way that it mimics the hosts' own tissue, and as a result is not attacked.(Olive) However, due to the increasing public health crisis of antibiotic resistant bacteria, this research is proving to be the most promising in developing new antibiotics to fight GAS bacteria.
References
Ferretti JJ, McShan WM, Ajdic D, Savic DJ, Savic G, Lyon K, Primeaux C, Sezate S, Suvorov AN, Kenton S, Lai HS, Lin SP, Qian Y, Jia HG, Najar FZ, Ren Q, Zhu H, Song L, White J, Yuan X, Clifton SW, Roe BA, McLaughlin R."Complete genome sequence of an M1 strain of Streptococcus pyogenes"., Proc Natl Acad Sci U S A, 2001 Apr 10;98(8):4658-63 http://www.ncbi.nlm.nih.gov/sites/entrez
Group A Streptococcus.http://www.dhpe.org/infect/strepa.html
Horiuchi K, Shiota S, Hatano T, Yoshida T, Kuroda T, Tsuchiya T. "Antimicrobial Activity of Oleanolic Acid from Salvia officinalis and Related Compounds on Vancomycin-Resistant Enterococci (VRE)." Biol Pharm Bull. 2007 Jun;30(6):1147-9. http://webct6web.ucsd.edu/webct/cobaltMainFrame.dowebct
Musser J. "The next chapter in reverse vaccinology." Nature Biotechnology 24, 157 - 158 (2006)doi:10.1038/nbt0206-157 http://www.nature.com/nbt/journal/v24/n2/full/nbt0206-157.html
Olive C. "Progress in M-protein-based subunit vaccines to prevent rheumatic fever and rheumatic heart disease." Curr Opin Mol Ther. 2007 Feb;9(1):25-34. http://webct6web.ucsd.edu/webct/cobaltMainFrame.dowebct
ovanka M. Voyich, Kevin R. Braughton, Daniel E. Sturdevant, Cuong Vuong, Scott D. Kobayashi, Stephen F. Porcella, Michael Otto, James M. Musser and Frank R. DeLeo1 "Engagement of the Pathogen Survival Response Used by Group A Streptococcus to Avert Destruction by Innate Host Defense." The Journal of Immunology, 2004, 173: 1194-1201. http://www.jimmunol.org/cgi/content/full/173/2/1194
Regev-Yochay G, Trzcinski K, Thompson CM, Malley R, Lipsitch M. "Interference between Streptococcus pneumoniae and Staphylococcus aureus: In vitro hydrogen peroxide-mediated killing by Streptococcus pneumoniae." J Bacteriol. 2006 Jul;188(13):4996-5001. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16788209&query_hl=38&itool=pubmed_docsum
Sandrini MP, Shannon O, Clausen AR, Bjorck L, Piskur J."DEOXYRIBONUCLEOSIDE KINASES ACTIVATE NUCLEOSIDE ANTIBIOTICS IN SEVERE PATHOGENIC BACTERIA."Antimicrob Agents Chemother. 2007 May 25 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17526755&itool=iconabstr&query_hl=10&itool=pubmed_docsum
Sat Sharma, MD, FRCPC, FACP, FCCP, DABSM, Program Director, Associate Professor, Department of Internal Medicine, Divisions of Pulmonary and Critical Care Medicine, University of Manitoba; Site Director of Respiratory Medicine, St Boniface General Hospital. Streptococcus Group A Infections. May 5, 2006. eMedicine http://www.emedicine.com/med/topic2184.htm#section~author_information
Tart AH, Walker MJ, Musser JM. New understanding of the group A Streptococcus pathogenesis cycle. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17524649&itool=iconabstr&query_hl=12&itool=pubmed_docsum
Tsuchiya N, Williams R. "Molecular Mimicry-Hypothesis or Reality?" Western Association of Physicians meeting. February 5-6, 1992. http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1011230&blobtype=pdf
Zhang S, Green NM, Sitkiewicz I, Lefebvre RB, Musser JM. "Identification and characterization of an antigen I/II family protein produced by group A Streptococcus." Infect Immun. 2006 Jul;74(7):4200-13. http://webct6web.ucsd.edu/webct/cobaltMainFrame.dowebct
edited KMG
