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The small RNA Teg41 is a pleiotropic regulator of virulence in Staphylococcus aureus

ABSTRACT: Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Ronan Carroll

LAB HEAD: Ronan Carroll

PROVIDER: PXD034014 | Pride | 2022-10-03

REPOSITORIES: Pride

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			Action	DRS
	20211105_Carroll_cytosol_WT-A.raw	Raw
	20211105_Carroll_cytosol_WT-B.raw	Raw
	20211105_Carroll_cytosol_WT-C.raw	Raw
	20211105_Carroll_cytosol_comp-A.raw	Raw
	20211105_Carroll_cytosol_comp-B.raw	Raw

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Project description:The success of Staphylococcus aureus as a pathogen results from the production of a wealth of virulence determinants that aid in immune evasion, host cell invasion and dissemination of infection. Given the niche specific roles of these factors in infection, their production is controlled by a complex network of regulatory factors. In a continued effort to understand this network, the present study is aimed at characterizing the role of the transcriptional regulator XdrA and its effects on S. aureus gene expression. Using an unbiased global analysis, we find that XdrA has a broad impact on gene expression, influencing the transcription of several important virulence determinants, and factors involved in gene regulation. When assessing the role of XdrA in virulence, we find that an xdrA mutant has an increased ability to survive in whole human blood, mediated in part by increased survival within neutrophils, and an upregulation in expression of several factors involved in immune evasion, including sbi, fnbpA and efb. Furthermore, the increased survival within neutrophils appears to result from an upregulation in expression of sodM, recA, and sae, all of which assist bacterial cells in combating the effects of oxidative stress. In addition to these changes, we find that the xdrA mutant has a decreased abundance of cytolytic toxins, likely resulting from changes in agr and sae activity. We suggest that the broad impact of XdrA on the expression of genes involved in immune evasion, DNA damage, and oxidative stress tolerance, collectively result in a survival advantage allowing for the increased ability to causes disease in vivo, when xdrA is disrupted. In sum, our findings shed new light on the role of XdrA and its seemingly novel influence on S. aureus survival during infection. The dataset contained herein was used to elucidate the whole shotgun secreted proteome (secretome) obtained from 5 hour (mid exponential phase) and 15 hour (stationary phase) planktonic cultures of Staphylococcus aureus USA300 LAC strain, and a derivative of this strain deficient in the gene encoding XdrA.

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The small RNA Teg41 is a pleiotropic regulator of virulence in Staphylococcus aureus

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