Regulatory gene mutation: a driving force behind group a Streptococcus strain- and serotype-specific variation.
Regulatory gene mutation: a driving force behind group a Streptococcus strain- and serotype-specific variation.
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DOI：
10.1111/mmi.13584
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发表时间：
2017-02
影响因子：
3.6
通讯作者：
Sumby P
中科院分区：
文献类型：
--
作者：
Sarkar P;Sumby P
来自多种细菌病原体的数据与突变频率高于基因组平均水平的调节因子编码基因一致。此类突变驱动菌株和类型（例如血清型、单倍型）特异性表型异质性，并且可能由于变异可能规避已建立的治疗和/或预防方案而挑战公共健康。在这里，我们使用人类细菌病原体 A 组链球菌（GAS；化脓性链球菌）作为模式生物，回顾了自然发生的调节基因突变的类型和调节、表型和疾病特异性后果。将讨论的菌株特异性调节突变包括通过增强免疫调节毒力因子的表达将分离株转化为高侵袭性形式的例子，以及促进生物体无症状携带的例子。关于血清型特异性调节突变的讨论集中在血清型 M3 GAS 分离株上，以及在该血清型中发现的调节网络的重新布线如何可能导致数十年来 M3 分离株与特别严重的侵袭性感染的流行病学关联。我们得出的结论是，突变在 GAS 发病机制中发挥着巨大作用，并且具有临床相关性。考虑到与调节基因突变相关的表型变异，对感染分离株中这些基因的快速检查可能会为潜在的患者并发症和治疗选择提供信息。 简短摘要 调节因子编码基因内突变的选择是细菌菌株和类型特异性表型异质性的主要驱动因素。在这里，我们回顾了人类细菌病原体 A 组链球菌中自然发生的调节基因突变的类型以及调节、表型和疾病特异性后果。我们得出的结论是，突变在 A 族链球菌发病机制中发挥着巨大作用，并且具有临床相关性。
Data from multiple bacterial pathogens are consistent with regulator-encoding genes having higher mutation frequencies than the genome average. Such mutations drive both strain- and type- (e.g. serotype, haplotype) specific phenotypic heterogeneity, and may challenge public health due to the potential of variants to circumvent established treatment and/or preventative regimes. Here, using the human bacterial pathogen the group A Streptococcus (GAS; S. pyogenes) as a model organism, we review the types and regulatory-, phenotypic-, and disease-specific consequences of naturally occurring regulatory gene mutations. Strain-specific regulator mutations that will be discussed include examples that transform isolates into hyper-invasive forms by enhancing expression of immunomodulatory virulence factors, and examples that promote asymptomatic carriage of the organism. The discussion of serotype-specific regulator mutations focuses on serotype M3 GAS isolates, and how the identified rewiring of regulatory networks in this serotype may be contributing to a decades old epidemiological association of M3 isolates with particularly severe invasive infections. We conclude that mutation plays an outsized role in GAS pathogenesis and has clinical relevance. Given the phenotypic variability associated with regulatory gene mutations, the rapid examination of these genes in infecting isolates may inform with respect to potential patient complications and treatment options. Abbreviated summary The selection of mutations within regulator-encoding genes is a major driver of bacterial strain-and type-specific phenotypic heterogeneity. Here, we review the types and regulatory-, phenotypic-, and disease-specific consequences of naturally occurring regulatory gene mutations in the human bacterial pathogen the group A Streptococcus. We conclude that mutation plays an outsized role in group A Streptococcus pathogenesis and has clinical relevance.