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Characterizing the transcriptional adaptation of Staphylococcus aureus to stationary phase growth.

ABSTRACT: Staphylococcus aureus is an important human pathogen that causes life-threatening infections, and is resistant to the majority of our antibiotic arsenal. This resistance is complicated by the observation that most antibacterial agents target actively growing cells, thus, proving ineffective against slow growing populations, such as cells within a biofilm or in stationary phase. Recently, our group generated updated genome annotation files for S. aureus that not only include protein-coding genes but also regulatory and small RNAs. As such, these annotation files were used to perform a transcriptomic analysis in order to understand the metabolic and physiological changes that occur during transition from active growth to stationary phase; with a focus on sRNAs. We observed ∼24% of protein-coding and 34% of sRNA genes displaying changes in expression by ≥3-fold. Collectively, this study adds to our understanding of S. aureus adaptation to nutrient-limiting conditions, and sheds new light onto the contribution of sRNAs to this process.

SUBMITTER: Weiss A

PROVIDER: S-EPMC5985488 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Characterizing the transcriptional adaptation of Staphylococcus aureus to stationary phase growth.

Weiss Andy A Broach William H WH Shaw Lindsey N LN

Pathogens and disease 20160508 5

Staphylococcus aureus is an important human pathogen that causes life-threatening infections, and is resistant to the majority of our antibiotic arsenal. This resistance is complicated by the observation that most antibacterial agents target actively growing cells, thus, proving ineffective against slow growing populations, such as cells within a biofilm or in stationary phase. Recently, our group generated updated genome annotation files for S. aureus that not only include protein-coding genes ...[more]

PMID: 27162210

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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.

Dataset Information

Characterizing the transcriptional adaptation of Staphylococcus aureus to stationary phase growth.

Publications

Characterizing the transcriptional adaptation of Staphylococcus aureus to stationary phase growth.

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