Dataset Information

Identification of novel mazEF/pemIK family toxin-antitoxin loci and their distribution in the Staphylococcus genus.

ABSTRACT: The versatile roles of toxin-antitoxin (TA) systems in bacterial physiology and pathogenesis have been investigated for more than three decades. Diverse TA loci in Bacteria and Archaea have been identified in genome-wide studies. The advent of massive parallel sequencing has substantially expanded the number of known bacterial genomic sequences over the last 5 years. In staphylococci, this has translated into an impressive increase from a few tens to a several thousands of available genomes, which has allowed us for the re-evalution of prior conclusions. In this study, we analysed the distribution of mazEF/pemIK family TA system operons in available staphylococcal genomes and their prevalence in mobile genetic elements. 10 novel m azEF/pemIK homologues were identified, each with a corresponding toxin that plays a potentially different and undetermined physiological role. A detailed characterisation of these TA systems would be exceptionally useful. Of particular interest are those associated with an SCCmec mobile genetic element (responsible for multidrug resistance transmission) or representing the joint horizontal transfer of TA systems and determinants of vancomycin resistance from enterococci. The involvement of TA systems in maintaining mobile genetic elements and the associations between novel mazEF/pemIK loci and those which carry drug resistance genes highlight their potential medical importance.

SUBMITTER: Bukowski M

PROVIDER: S-EPMC5647390 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Identification of novel mazEF/pemIK family toxin-antitoxin loci and their distribution in the Staphylococcus genus.

Bukowski Michal M Hyz Karolina K Janczak Monika M Hydzik Marcin M Dubin Grzegorz G Wladyka Benedykt B

Scientific reports 20171018 1

The versatile roles of toxin-antitoxin (TA) systems in bacterial physiology and pathogenesis have been investigated for more than three decades. Diverse TA loci in Bacteria and Archaea have been identified in genome-wide studies. The advent of massive parallel sequencing has substantially expanded the number of known bacterial genomic sequences over the last 5 years. In staphylococci, this has translated into an impressive increase from a few tens to a several thousands of available genomes, whi ...[more]

PMID: 29044211

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Project description:Bacterial cells respond to environmental stresses by modulating their gene expression and adjusting their proteome. In Staphylococcus aureus, selective degradation by ClpP protease eliminates damaged proteins and regulates the abundance of functional proteins such as many important stress-induced transcriptional regulators. Degradation by ClpP requires the unfolding activity of partner Clp ATPases, such as ClpX and ClpC, and assistance of substrate-specific adaptor proteins such as YjbH and TrfA. Herein, we demonstrated that YjbH is aggregated in response to growth stress stimuli, such as oxidative and antibiotic stresses. In consequence, its function as an adaptor protein is compromised. YjbH controls the degradation of the stress-induced transcriptional regulator, Spx. Aggregated YjbH cannot assist Spx degradation, which results in Spx accumulation. We discovered that depending on the stress stimulus, Spx can be soluble or insoluble, and, consequently, transcriptionally active or inactive. Therefore, Spx accumulation and solubility are key components governing activation of Spx-dependent genes. Spx positively regulates expression of a ClpCP adaptor protein TrfA. TrfA in turn is required for degradation of MazE antitoxin, the unstable component of the MazEF toxin-antitoxin system, that neutralizes the endoribonuclease activity of MazF toxin. Bacterial toxin-antitoxin systems are associated with dormancy and tolerance to antibiotics that are related to chronic and relapsing infections, and it is at present a key unresolved problem in medicine. MazF activity was linked to growth stasis, yet the precise environmental signals that trigger MazE degradation and MazF activation are poorly understood. Here we propose a model where YjbH serves as a sensor of environmental stresses for downstream regulation of MazEF activity. YjbH aggregation, soluble Spx, and TrfA, coordinately control MazE antitoxin levels and consequently MazF toxin activity. This model implies that certain stress conditions culminate in modulation of MazF activity resulting in growth stasis during in vivo infections.

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Dataset Information

Identification of novel mazEF/pemIK family toxin-antitoxin loci and their distribution in the Staphylococcus genus.

Publications

Identification of novel mazEF/pemIK family toxin-antitoxin loci and their distribution in the Staphylococcus genus.

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