Dataset Information

RsaC sRNA modulates the oxidative stress response of Staphylococcus aureus during manganese starvation.

ABSTRACT: The human opportunistic pathogen Staphylococcus aureus has developed multiple strategies to adapt to various environments, to fight and escape the immune system, to spread and persist in host tissues. It is responsible for numerous diseases ranging from benign skin infections to more serious such as endocarditis or septicemia. The pathogenicity is due to the production of a multitude of virulence factors, whose synthesis is finely regulated by a combination of regulatory proteins and small non-coding RNAs (sRNAs). Our study reveals an unexpected function of an atypical sRNA, RsaC, which is at the heart of networks controlling defence responses to oxidative stress, manganese import and nutrition immunity. This work highlights a novel mechanism required for S. aureus to survive into its host.

INSTRUMENT(S): TripleTOF 5600, Q Exactive

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Johana Chicher

LAB HEAD: David Lalaouna

PROVIDER: PXD013225 | Pride | 2019-11-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2015_07_A.Tomasini_NewrsaC_WT1-1000ng.mgf	Mgf
	2015_07_A.Tomasini_NewrsaC_WT1-1000ng.wiff	Wiff
	2015_07_A.Tomasini_NewrsaC_WT1-1000ng.wiff.scan	Wiff
	2015_07_A.Tomasini_NewrsaC_WT2-1000ng.mgf	Mgf
	2015_07_A.Tomasini_NewrsaC_WT2-1000ng.wiff	Wiff

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RsaC sRNA modulates the oxidative stress response of Staphylococcus aureus during manganese starvation.

Lalaouna David D Baude Jessica J Wu Zongfu Z Tomasini Arnaud A Chicher Johana J Marzi Stefano S Vandenesch François F Romby Pascale P Caldelari Isabelle I Moreau Karen K

Nucleic acids research 20191001 18

The human opportunistic pathogen Staphylococcus aureus produces numerous small regulatory RNAs (sRNAs) for which functions are still poorly understood. Here, we focused on an atypical and large sRNA called RsaC. Its length varies between different isolates due to the presence of repeated sequences at the 5' end while its 3' part is structurally independent and highly conserved. Using MS2-affinity purification coupled with RNA sequencing (MAPS) and quantitative differential proteomics, sodA mRNA ...[more]

PMID: 31504767

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Project description:Staphylococcus aureus thymidine-dependent small-colony variants (TD-SCVs) are frequently isolated from patients with chronic S. aureus infections after long-term treatment with trimethoprim-sulfamethoxazole (TMP-SMX). In TD-SCVs, mutations of thymidylate synthase (thyA, TS), essential for DNA synthesis, occur. However, it has never been shown, that TMP-SMX is responsible for the induction and selection of TD-SCVs. Short-term exposure of TMP-SMX induced the TD-SCV phenotype morphologically as shown in transmission electron-microscopy and on the transcriptional level by qRT-PCR in wild-type S. aureus, while selection of TD-SCVs with thyA mutations occurred only rarely after long-term exposure. In reversion experiments with clinical TD-SCVs, all revertants revealed compensating mutations at the initially identified mutation site. Whole DNA microarray analysis of a thyA deletion mutant (M-bM-^HM-^FthyA), which exhibited the typical TD-SCV phenotype, identified tremendous alterations compared to the wild-type. Important virulence regulators such as agr, arlRS, sarA and major virulence determinants including hla, hlb, sspA, sspB and geh were down-regulated, while genes associated with the colonization capacity like fnbA, fnbB, spa, clfB, sdrC and sdrD were up-regulated. The expression of genes involved in pyrimidine and purine metabolism as well as in nucleotide interconversion changed significantly. The M-bM-^HM-^FthyA-mutant was attenuated in virulence in both, a Caenorhabditis elegans killing model and an acute murine pneumonia model. Furthermore, competition experiments in vitro and in vivo (using a chronic pneumonia mouse model) revealed a survival and growth advantage of the M-bM-^HM-^FthyA-mutant under low thymidine conditions and TMP-SMX exposure. In conclusion, our results clearly show for the first time that TMP-SMX induces the TD-SCV phenotype after short-term exposure in S. aureus and that long-term exposure selects thyA mutations providing an advantage for TD-SCVs under specified conditions. Thus, our results help to understand the dynamic processes of induction and selection of S. aureus TD-SCVs during TMP-SMX exposure. 18 independent samples were analysed; for each isolate and time point 3 replicates were performed

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Dataset Information

RsaC sRNA modulates the oxidative stress response of Staphylococcus aureus during manganese starvation.

Dataset's files

Publications

RsaC sRNA modulates the oxidative stress response of Staphylococcus aureus during manganese starvation.

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