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{{Short description|Type of regulator gene}}
'''Accessory gene regulator (agr)''' is a complex 4 [[gene locus]] that is a global [[Regulator gene|regulator]] of [[virulence]] in ''[[Staphylococcus aureus]]''.<ref>{{cite journal | vauthors = Recsei P, Kreiswirth B, O'Reilly M, Schlievert P, Gruss A, Novick RP | title = Regulation of exoprotein gene expression in Staphylococcus aureus by agar | journal = Molecular & General Genetics | volume = 202 | issue = 1 | pages = 58–61 | date = January 1986 | pmid = 3007938 | doi = 10.1007/BF00330517 | s2cid = 8592594 }}</ref><ref>{{cite journal | vauthors = Gomes-Fernandes M, Laabei M, Pagan N, Hidalgo J, Molinos S, Villar Hernandez R, Domínguez-Villanueva D, Jenkins AT, Lacoma A, Prat C | display-authors = 6 | title = Accessory gene regulator (Agr) functionality in Staphylococcus aureus derived from lower respiratory tract infections | journal = PLOS ONE | volume = 12 | issue = 4 | article-number = e0175552 | date = 2017-04-14 | pmid = 28410390 | pmc = 5391941 | doi = 10.1371/journal.pone.0175552 | bibcode = 2017PLoSO..1275552G | doi-access = free }}</ref><ref name="pmid29422887">{{cite journal | vauthors = Tan L, Li SR, Jiang B, Hu XM, Li S | title = Therapeutic Targeting of the Staphylococcus aureus Accessory Gene Regulator (agr) System | journal = Frontiers in Microbiology | volume = 9 | article-number = 55 | date = 2018 | pmid = 29422887 | pmc = 5789755 | doi = 10.3389/fmicb.2018.00055 | doi-access = free }}</ref> It encodes a two-component transcriptional [[Quorum sensing|quorum-sensing]] (QS) system activated by an autoinducing, thiolactone-containing cyclic peptide (AIP).<ref name="MicrobioJ">{{cite journal | vauthors = Williams P | title = Microbial Primer: agr-mediated quorum sensing in Gram-positive pathogens | journal = Microbiology | volume = 171 | issue = 7 | page = 001590 | date = July 2025| pmid = 40742629 | pmc = 12312760 | doi = 10.1099/mic.0.001590 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ji G, Beavis RC, Novick RP | title = Cell density control of staphylococcal virulence mediated by an octapeptide pheromone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 26 | pages = 12055–9 | date = December 1995 | pmid = 8618843 | pmc = 40295 | doi = 10.1073/pnas.92.26.12055 | bibcode = 1995PNAS...9212055J | doi-access = free }}</ref>

Agr occurs in 4 allelic subtypes that have an important role in staphylococcal evolution.<ref>{{cite journal | vauthors = Wright JS, Traber KE, Corrigan R, Benson SA, Musser JM, Novick RP | title = The agr radiation: an early event in the evolution of staphylococci | journal = Journal of Bacteriology | volume = 187 | issue = 16 | pages = 5585–94 | date = August 2005 | pmid = 16077103 | pmc = 1196086 | doi = 10.1128/JB.187.16.5585-5594.2005 }}</ref><ref name=":0">{{cite journal | vauthors = Jarraud S, Lyon GJ, Figueiredo AM, Lina G, Gérard L, Vandenesch F, Etienne J, Muir TW, Novick RP | display-authors = 6 | title = Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus | journal = Journal of Bacteriology | volume = 182 | issue = 22 | pages = 6517–22 | date = November 2000 | pmid = 11053400 | pmc = 94802 | doi = 10.1128/jb.182.22.6517-6522.2000 }}</ref> The corresponding AIPs are mutually cross-inhibitory, which may enhance the evolutionary separation of the 4 groups.<ref name=":0" /><ref>{{cite journal | vauthors = Ji G, Beavis R, Novick RP | title = Bacterial interference caused by autoinducing peptide variants | journal = Science | volume = 276 | issue = 5321 | pages = 2027–30 | date = June 1997 | pmid = 9197262 | doi = 10.1126/science.276.5321.2027 }}</ref> The ''agr'' receptor, AgrC, is a model histidine phosphokinase (HPK) that has been used to decipher the molecular mechanism of [[signal transduction]].<ref name=":1">{{cite journal | vauthors = Wang B, Zhao A, Xie Q, Olinares PD, Chait BT, Novick RP, Muir TW | title = Functional Plasticity of the AgrC Receptor Histidine Kinase Required for Staphylococcal Virulence | journal = Cell Chemical Biology | volume = 24 | issue = 1 | pages = 76–86 | date = January 2017 | pmid = 28065658 | pmc = 5697745 | doi = 10.1016/j.chembiol.2016.12.008 }}</ref> AIP binding to the extracellular domain of AgrC causes twisting of the intracellular a-helical domain so as to enable trans-phosphorylation of the active site histidine; the inhibitory AIPs cause the α-helical domain to twist in the opposite direction, preventing trans-phosphorylation.<ref name=":1" /> The ''agr'' QS circuit autoactivates transcription of ''agrA'' which, in turn upregulates the phenol-souble modulins.<ref>{{cite journal | vauthors = Chatterjee SS, Chen L, Joo HS, Cheung GY, Kreiswirth BN, Otto M | title = Distribution and regulation of the mobile genetic element-encoded phenol-soluble modulin PSM-mec in methicillin-resistant Staphylococcus aureus | journal = PLOS ONE | volume = 6 | issue = 12 | article-number = e28781 | date = 2011-12-12 | pmid = 22174895 | pmc = 3236207 | doi = 10.1371/journal.pone.0028781 | bibcode = 2011PLoSO...628781C | veditors = Horsburgh MJ | doi-access = free }}</ref> More importantly, it activates transcription of a divergently oriented promoter whose transcript, known as [[RNAIII]],<ref name=":2">{{cite journal | vauthors = Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B, Moghazeh S | title = Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule | journal = The EMBO Journal | volume = 12 | issue = 10 | pages = 3967–75 | date = October 1993 | pmid = 7691599 | doi = 10.1002/j.1460-2075.1993.tb06074.x | pmc = 413679 }}</ref> is a 514 nt regulatory RNA that encodes δ-hemolysin and is the major effector of the ''agr'' regulon.<ref name=":2" /> [[RNAIII]] acts by [[antisense]] inhibition or activation of target gene translation. In vitro, early in growth, genes encoding surface proteins important for adhesion and immune evasion (such as ''spa'' – encoding protein''A''<ref>{{cite journal | vauthors = Benito Y, Kolb FA, Romby P, Lina G, Etienne J, Vandenesch F | title = Probing the structure of RNAIII, the Staphylococcus aureus agr regulatory RNA, and identification of the RNA domain involved in repression of protein A expression | journal = RNA | volume = 6 | issue = 5 | pages = 668–79 | date = May 2000 | article-number = S1355838200992550 | pmid = 10836788 | pmc = 1369947 | doi = 10.1017/S1355838200992550 }}</ref>) are expressed, enabling the organism to gain a foothold. Later in growth, these genes are down-regulated by [[RNAIII]] and those encoding toxins, hemolysins and other virulence-related proteins, are turned on, enabling the organism to establish and promulgate its pathological programs, such as abscess formation.<ref>{{cite journal | vauthors = Novick RP | title = Autoinduction and signal transduction in the regulation of staphylococcal virulence | journal = Molecular Microbiology | volume = 48 | issue = 6 | pages = 1429–49 | date = June 2003 | pmid = 12791129 | doi = 10.1046/j.1365-2958.2003.03526.x | s2cid = 6847208 | doi-access = free }}</ref> It is assumed that this program operates in vivo as well. As ''agr'' is essential for staphylococcal contagion,<ref>{{cite journal | vauthors = Shopsin B, Eaton C, Wasserman GA, Mathema B, Adhikari RP, Agolory S, Altman DR, Holzman RS, Kreiswirth BN, Novick RP | display-authors = 6 | title = Mutations in agr do not persist in natural populations of methicillin-resistant Staphylococcus aureus | journal = The Journal of Infectious Diseases | volume = 202 | issue = 10 | pages = 1593–9 | date = November 2010 | pmid = 20942648 | doi = 10.1086/656915 | doi-access = free }}</ref> ''agr-''defective mutants are not contagious, but enable the organism's long-term survival in chronic conditions such as surgical implant infections, [[osteomyelitis]] or the infected lung in [[cystic fibrosis]]. In keeping with this behavior, mutations inactivating ''agr'' function enhance the stability of [[biofilm]]s,<ref>{{cite journal | vauthors = Kong KF, Vuong C, Otto M | title = Staphylococcus quorum sensing in biofilm formation and infection | journal = International Journal of Medical Microbiology | volume = 296 | issue = 2–3 | pages = 133–9 | date = April 2006 | pmid = 16487744 | doi = 10.1016/j.ijmm.2006.01.042 }}</ref> which are key to the maintenance of chronic infections.

''Agr'' is widely conserved among [[Bacillota]]<ref>{{cite journal | vauthors = Wuster A, Babu MM | title = Conservation and evolutionary dynamics of the agr cell-to-cell communication system across firmicutes | journal = Journal of Bacteriology | volume = 190 | issue = 2 | pages = 743–6 | date = January 2008 | pmid = 17933897 | pmc = 2223712 | doi = 10.1128/JB.01135-07 }}</ref> and has a well-defined role in virulence regulation in several genera, especially ''[[Listeria]]'' and ''[[Clostridia]]''.

== References ==
{{Reflist}}

[[Category:Gene expression]]
[[Category:Genetics]]
[[Category:Virology]]

Accessory gene regulator - История изменений

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