Copper intoxication in group b Streptococcus triggers transcriptional activation of the cop operon that contributes to enhanced virulence during acute infection

Sullivan, Matthew J., Goh, Kelvin G. K., Gosling, Dean, Katupitiya, Lahiru and Ulett, Glen C. (2021) Copper intoxication in group b Streptococcus triggers transcriptional activation of the cop operon that contributes to enhanced virulence during acute infection. Journal of Bacteriology, 203 (19). ISSN 0021-9193

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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 (RNAseq) 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.

Item Type: Article
Additional Information: Funding Information: This work was supported by a Project Grant from the National Health and Medical Research Council (NHMRC) Australia (grant APP1146820 to G.C.U.). Publisher Copyright: © 2021 American Society for Microbiology. All rights reserved.
Uncontrolled Keywords: bacterial pathogenesis,copa,copper efflux,group b streptococcus,metal ions,metallobiology,microbiology,molecular biology ,/dk/atira/pure/subjectarea/asjc/2400/2404
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Depositing User: LivePure Connector
Date Deposited: 15 Aug 2022 11:30
Last Modified: 02 Oct 2022 21:33
URI: https://ueaeprints.uea.ac.uk/id/eprint/87252
DOI: 10.1128/JB.00315-21

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