The cop operon is required for copper homeostasis and contributes to virulence in Streptococcus pneumoniae
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ABSTRACT:
PROVIDER: PRJNA143377 | ENA |
REPOSITORIES: ENA
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Project description:High levels of copper are toxic and therefore bacteria must limit free intracellular levels to prevent cellular damage. In this study, we show that a number of pneumococcal genes are differentially regulated by copper, including an operon encoding a CopY regulator, a protein of unknown function (CupA) and a P1-type ATPase, CopA, which is conserved in all sequenced Streptococcus pneumoniae strains. Transcriptional analysis demonstrated that the cop operon is induced by copper in vitro, repressed by the addition of zinc and is autoregulated by the copper-responsive CopY repressor protein. We also demonstrate that the CopA ATPase is a major pneumococcal copper resistance mechanism and provide the first evidence that the CupA protein plays a role in copper resistance. Our results also show that copper homeostasis is important for pneumococcal virulence as the expression of the cop operon is induced in the lungs and nasopharynx of intranasally infected mice, and a copA(-) mutant strain, which had decreased growth in high levels of copper in vitro, showed reduced virulence in a mouse model of pneumococcal pneumonia. Furthermore, using the copA(-) mutant we observed for the first time in any bacteria that copper homeostasis also appears to be required for survival in the nasopharynx. This SuperSeries is composed of the SubSeries listed below.
2011-07-10 | GSE30415 | GEO
Project description:Copper is both essential and toxic to living beings, which therefore tightly control its intracellular concentration. At the host-pathogen interface, copper is used by phagocytic cells to kill invading microorganisms. We investigated copper homeostasis in the whooping cough agent Bordetella pertussis, which lives in the human respiratory mucosa and has no environmental reservoir. B. pertussis has considerably streamlined copper homeostasis mechanisms relative to other Gram-negative bacteria. Its single remaining defense line against copper intoxication consists in a metallochaperone diverted for copper passivation and two enzymes involved in peroxide detoxification, which together fight two stresses encountered in phagolysosomes. The three proteins are encoded by an original, composite operon assembled in an environmental ancestor and which is under sensitive control by copper. Interestingly, this system appears to play a role in persistent infection in the nasal cavity of B. pertussis-infected mice. Combining responses to co-occurring stresses in a tailored operon reveals a new strategy adopted by a host-restricted pathogen to optimize survival at minimal energy expenditure.
2021-09-09 | PXD020900 | Pride
Project description:Copper is essential for both innate and adaptive immune function and copper resistance has emerged as an important determinant of virulence of microbial pathogens. In the human pathogen Streptococcus pneumoniae (Spn), cytoplasmic copper resistance is mediated by an operon encoding the copper-responsive repressor CopY, CupA, of unknown function, and CopA, a copper effluxing P1B-type ATPase. We show that CupA is a novel cell membrane-anchored Cu(I) chaperone for CopA, and that a Cu(I)-binding competent, membrane-localized CupA, like CopA, is obligatory for copper resistance.
2013-05-24 | GSE39176 | GEO
Project description: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.
| S-EPMC8447484 | biostudies-literature
Project description:We examined the whole-genome transcriptional response of E. faecalis wild-type (WT) and copy mutant cells exposed to non toxic Cu excess. The analysis was focused in those genes which changed significantly their expression levels in the Cu-treated cells when compared to their untreated counterparts. The results indicated that after 3 h at 0.5 mM CuSO4, WT cells exhibited a significant increment of Cu content and the induction of three genes of cop operon along with other 142 genes. The comparison with the copY mutant exposed to Cu showed an extensive overlapping of transcriptional changes suggesting that other transcription factors may be mediating the response to Cu. Associated manuscript The global response of Enterococcus faecalis to copper exposure
2011-02-14 | GSE20453 | GEO
Project description:Panicum virgatum COP Resequencing genome sequencing
| PRJNA334728 | ENA
Project description:The transcription factor Mac1 is a key regulator of copper homeostasis, controlling the transcriptional response to copper-limiting conditions in fungi. It has been described as a virulence factor in human pathogens such as Candida albicans and Aspergillus fumigatus, but surprisingly its role in plant pathogenesis is poorly understood. Targeted deletion of Mac1 in the soilborne pathogen Fusarium oxisporum results in an inability to grow under copper-limited conditions and kills tomato plants. The aim of this RNA-seq analysis is to elucidate the role of Mac1 in gene regulation under copper starvation and during infection of tomato plants by F. oxysporum.
2024-11-07 | GSE243247 | GEO
Project description:We studied the transcriptome changes of Vibrio parahaemolyticus under normal culture condition and copper stress by RNA sequencing. The data showed that genes in copA and cusFABC operon were significantly upregulated by copper.
2024-08-01 | GSE268489 | GEO
Project description:First we developed a new, simple, and robust assay called CoP (Column Purified chromatin) for profiling of accessible regions by directly purifying fragmentized crosslinked chromatin with DNA purification column. The CoP chromatin regions by CoP-seq are consistent with the accessible regions detected by ATAC-seq and FARIE-seq. Then we integrated CoP-seq and Hi-C technique (Hi-CoP) for interactions of accessible chromatin regions which represent active cis-regulatory elements in cells. Our data showed that Hi-CoP assay can robustly detect interactions of regulatory regions.
2020-01-29 | GSE144412 | GEO
Project description:Copper is both essential and toxic to living beings, which therefore tightly control its intracellular concentration. At the host-pathogen interface, copper is used by phagocytic cells to kill invading microorganisms. We investigated copper homeostasis in the whooping cough agent Bordetella pertussis, which lives in the human respiratory mucosa and has no environmental reservoir. B. pertussis has considerably streamlined copper homeostasis mechanisms relative to other Gram-negative bacteria. Its single remaining defense line against copper intoxication consists in a metallochaperone diverted for copper passivation and two enzymes involved in peroxide detoxification, which together fight two stresses encountered in phagolysosomes. The three proteins are encoded by an original, composite operon assembled in an environmental ancestor and which is under sensitive control by copper. Interestingly, this system appears to play a role in persistent infection in the nasal cavity of B. pertussis-infected mice. Combining responses to co-occurring stresses in a tailored operon reveals a new strategy adopted by a host-restricted pathogen to optimize survival at minimal energy expenditure.
2020-10-27 | GSE145049 | GEO