Genetics of Group A Streptococci

Genetics of Group A Streptococci
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DOI:
10.1128/microbiolspec.gpp3-0056-2018
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发表时间:
2019-03-01
影响因子:
3.7
通讯作者:
Caparon, Michael
Caparon, Michael
中科院分区:
生物学1区
文献类型:
--
作者:
Cho, Kyu Hong;Port, Gary C.;Caparon, Michael

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化脓性链球菌(A组链球菌)是显着的,在大量的疾病,它可以在人类中引起的,并为大量的链球菌因子,已被确定为这些疾病的潜在毒力决定因素。一个挑战是将潜在毒力因子的功能与特定疾病的发病机制联系起来。一个令人兴奋的进展是复杂的遗传系统的发展,用于构建靶向S.化脓性链球菌基因,可用于测试关于这些基因在发病机制中的特定假设。这将有助于从机制上理解特定基因功能如何促进每种链球菌疾病的发病机制。自从第一个S。化脓性链球菌基因组于2001年完成,数百个完整的基因组序列和草图已被保存。现在我们知道平均S。化脓性链球菌基因组约1.85Mb,编码1,800个基因,其中大部分基因在致病中的功能仍有待阐明。然而,用于操纵S.化脓性链球菌基因组现在为个体S.化脓性疾病,这可能导致更复杂和有针对性的治疗干预措施的发展。本文介绍了这些基因工具,包括基因改造的方法及其应用。
Streptococcus pyogenes (group A streptococcus) is remarkable in terms of the large number of diseases it can cause in humans and for the large number of streptococcal factors that have been identified as potential virulence determinants for these diseases. A challenge is to link the function of potential virulence factors to the pathogenesis of specific diseases. An exciting advance has been the development of sophisticated genetic systems for the construction of loss-of-function, conditional, hypomorphic, and gain-of-function mutations in targeted S. pyogenes genes that can be used to test specific hypotheses regarding these genes in pathogenesis. This will facilitate a mechanistic understanding of how a specific gene function contributes to the pathogenesis of each streptococcal disease. Since the first S. pyogenes genome was completed in 2001, hundreds of complete and draft genome sequences have been deposited. We now know that the average S. pyogenes genome is approximately 1.85Mb and encodes similar to 1,800 genes and that the function of most of those genes in pathogenesis remains to be elucidated. However, advances in the development of a variety of genetic tools for manipulation of the S. pyogenes genome now provide a platform for the interrogation of gene/phenotype relationships for individual S. pyogenes diseases, which may lead to the development of more sophisticated and targeted therapeutic interventions. This article presents an overview of these genetic tools, including the methods of genetic modification and their applications.