Copper Intoxication in Group B Streptococcus Triggers Transcriptional Activation of the cop Operon That Contributes to Enhanced Virulence during Acute Infection
Copper Intoxication in Group B Streptococcus Triggers Transcriptional Activation of the cop Operon That Contributes to Enhanced Virulence during Acute Infection
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B 族链球菌中的铜中毒会触发 cop 操纵子的转录激活，从而增强急性感染期间的毒力
DOI：
10.1128/jb.00315-21
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发表时间：
2021
影响因子：
3.2
通讯作者：
G. Ulett
中科院分区：
文献类型：
--
作者：
M. Sullivan;K. Goh;D. Gosling;L. Katupitiya;G. Ulett
了解细菌如何管理细胞水平的金属离子，如铜，有助于解释微生物细胞如何在不同的压力环境中生存。我们显示机会致病菌群B链球菌（GBS）通过包括铜操纵子的基因的活动来实现细胞内铜的稳态，并且我们描述了这如何帮助GBS在应激环境中生存，包括在哺乳动物宿主中全身性播散感染期间。摘要细菌可以利用铜作为微量元素来支持细胞过程，然而，过量的铜会使细菌中毒。在这里，我们的特点铜操纵子在B组链球菌（GBS），并建立其在逃避铜中毒和响应铜胁迫的毒力的作用。铜胁迫条件下，生长的GBS突变体缺陷的copA铜出口严重受损。GBS生存铜胁迫反映了CopY解阻遏的CopA外排系统的机制。然而，这两种突变体都没有减弱巨噬细胞的细胞内存活。通过RNA测序（RNA-seq）分析对Cu的全局转录响应揭示了包括多种金属的稳态的应激特征。铜胁迫诱导的基因包括推定的金属转运锰进口，而铁出口系统被压制。此外，copA促进GBS在播散性感染后在小鼠血液、肝脏和脾脏中定殖的能力。总之，这些研究结果表明，GBS copA介导的铜中毒通过调节铜敏感转录抑制copY的阻力。GBS中的Cu胁迫反应反映了增强毒力的转录特征，并且代表了细菌在不同环境中生存能力的重要部分。了解细菌如何管理细胞水平的金属离子，如铜，有助于解释微生物细胞如何在不同的压力环境中生存。我们显示机会致病菌群B链球菌（GBS）通过包括铜操纵子的基因的活动来实现细胞内铜的稳态，并且我们描述了这如何帮助GBS在应激环境中生存，包括在哺乳动物宿主中全身性播散感染期间。
Understanding how bacteria manage cellular levels of metal ions, such as copper, helps to explain how microbial cells can survive in different stressful environments. We show the opportunistic pathogen group B streptococcus (GBS) achieve homeostasis of intracellular copper through the activities of the genes that comprise the cop operon, and we describe how this helps GBS survive in stressful environments, including in the mammalian host during systemic disseminated infection. ABSTRACT Bacteria can utilize copper (Cu) as a trace element to support cellular processes; however, excess Cu can intoxicate bacteria. Here, we characterize the cop operon in group B streptococcus (GBS) and establish its role in evasion of Cu intoxication and the response to Cu stress on virulence. Growth of a GBS mutant deficient in the copA Cu exporter was severely compromised under Cu stress conditions. GBS survival of Cu stress reflected a mechanism of CopY derepression of the CopA efflux system. However, neither mutant was attenuated for intracellular survival in macrophages. Analysis of global transcriptional responses to Cu by RNA sequencing (RNA-seq) revealed a stress signature encompassing homeostasis of multiple metals. Genes induced by Cu stress included putative metal transporters for manganese import, whereas a system for iron export was repressed. In addition, copA promoted the ability of GBS to colonize the blood, liver, and spleen of mice following disseminated infection. Together, these findings show that GBS copA mediates resistance to Cu intoxication via regulation by the Cu-sensing transcriptional repressor copY. Cu stress responses in GBS reflect a transcriptional signature that heightens virulence and represents an important part of the bacterium’s ability to survive in different environments. IMPORTANCE Understanding how bacteria manage cellular levels of metal ions, such as copper, helps to explain how microbial cells can survive in different stressful environments. We show the opportunistic pathogen group B streptococcus (GBS) achieve homeostasis of intracellular copper through the activities of the genes that comprise the cop operon, and we describe how this helps GBS survive in stressful environments, including in the mammalian host during systemic disseminated infection.
影响因子：
--
作者：
FLEMING, RE;WHITMAN, IP;GITLIN, JD
通讯作者：
GITLIN, JD
DOI：
10.1073/pnas.97.2.652
发表时间：
2000-01-18
影响因子：
11.1
作者：
Rensing, C;Fan, B;Rosen, BP
通讯作者：
Rosen, BP
DOI：
10.1039/c4mt00327f
发表时间：
2015-06
期刊：
Metallomics : integrated biometal science
影响因子：
--
作者：
Ladomersky E;Petris MJ
通讯作者：
Petris MJ