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Staphylococcus aureus responds to physiologically relevant temperature changes by altering its global transcript and protein profile

ABSTRACT: Staphylococcus aureus is an opportunistic pathogen that colonizes the anterior nares of about 30-50% of the population. Colonization is most often asymptomatic, however, self-inoculation through inhalation, ingestion, or an open wound, can give rise to potentially fatal infections of the deeper tissues and blood. Like all bacteria, S. aureus is able to sense and respond to environmental cues and modify gene expression to adapt to specific environmental conditions. The transition of S. aureus from the nares to the deeper tissues and blood is accompanied by a number of changes in environmental conditions, such as nutrient availability, pH, and temperature. On average, the human anterior nares are 34 ˚C while a healthy individual maintains a core body temperature of 37 ˚C. In this study we investigate the response of S. aureus to changing temperature. Transcriptomics and proteomics were performed on S. aureus cultures growing at three physiologically relevant temperatures, 34˚C (nares), 37˚C (body), and 40˚C (pyrexia), to determine if small scale, biologically meaningful alterations in temperature have an impact on S. aureus gene expression. Results show that small but definite temperature changes elicit a large-scale restructuring of the S. aureus transcriptome and proteome. We demonstrate that these changes have physiological relevance through phenotypic analyses. Finally, using a human epithelial cell line infection assay, we investigate the impact that temperature dependent alterations in gene expression have on S. aureus pathogenesis and demonstrate decreased intracellular invasion of S. aureus cells grown at 34˚C. Collectively, our results demonstrate that small but biologically meaningful alterations in temperature can influence on S. aureus gene expression and may be a major contributor to the transition from a commensal to pathogen.

ORGANISM(S): Staphylococcus aureus

PROVIDER: GSE162697 | GEO | 2021/03/09

REPOSITORIES: GEO

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Project description:Becker2005 - Genome-scale metabolic network of Staphylococcus aureus (iSB619) This model is described in the article: Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation. Becker SA, Palsson BØ. BMC Microbiol. 2005; 5: 8 Abstract: BACKGROUND: Several strains of bacteria have sequenced and annotated genomes, which have been used in conjunction with biochemical and physiological data to reconstruct genome-scale metabolic networks. Such reconstruction amounts to a two-dimensional annotation of the genome. These networks have been analyzed with a constraint-based formalism and a variety of biologically meaningful results have emerged. Staphylococcus aureus is a pathogenic bacterium that has evolved resistance to many antibiotics, representing a significant health care concern. We present the first manually curated elementally and charge balanced genome-scale reconstruction and model of S. aureus' metabolic networks and compute some of its properties. RESULTS: We reconstructed a genome-scale metabolic network of S. aureus strain N315. This reconstruction, termed iSB619, consists of 619 genes that catalyze 640 metabolic reactions. For 91% of the reactions, open reading frames are explicitly linked to proteins and to the reaction. All but three of the metabolic reactions are both charge and elementally balanced. The reaction list is the most complete to date for this pathogen. When the capabilities of the reconstructed network were analyzed in the context of maximal growth, we formed hypotheses regarding growth requirements, the efficiency of growth on different carbon sources, and potential drug targets. These hypotheses can be tested experimentally and the data gathered can be used to improve subsequent versions of the reconstruction. CONCLUSION: iSB619 represents comprehensive biochemically and genetically structured information about the metabolism of S. aureus to date. The reconstructed metabolic network can be used to predict cellular phenotypes and thus advance our understanding of a troublesome pathogen. This model is hosted on BioModels Database and identified by: MODEL1507180070. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Staphylococcus aureus responds to physiologically relevant temperature changes by altering its global transcript and protein profile

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