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.

Prevalence of Antibiotic and Heavy Metal Resistance Determinants and Virulence-Related Genetic Elements in Plasmids of Staphylococcus aureus

“…In fact, the role of TA systems, in the context of stable genetic material maintenance in bacteria, is well-documented (Tsuchimoto et al, 1988; Sobecky et al, 1996; del Solar et al, 1998; Van Melderen and Saavedra De Bast, 2009; Bukowski et al, 2011, 2013). A number of recent reports point out their possible importance for drug resistance dissemination as well, for instance among enterococci (Moritz and Hergenrother, 2007; Rosvoll et al, 2010; Bukowski et al, 2017). However, it still seems that their role in this phenomenon has yet not received due attention.…”

Targeting Type II Toxin–Antitoxin Systems as Antibacterial Strategies

“…Furthermore, comparative studies of the distribution of TA systems in mycobacteria have demonstrated the variability of TA loci between different M. tuberculosis lineages, and led to the discovery of putative novel TA systems [ 42 , 43 ]. Similarly, the body of knowledge about the TA systems of S. aureus [ 44 ] was recently expanded by several studies providing insights into the association between the TA systems landscape and strain phenotypes [ 45 , 46 , 47 , 48 ]. A recent in-depth analysis of the diversity and distribution of type II and type IV TA systems in the genomes of K. pneumoniae species complex identified several novel toxins and demonstrated the co-occurrence of TA loci and clinically relevant genes [ 49 ].…”

Expression of Type II Toxin/Antitoxin systems and ClpP protease of Methicillin-Resistant Staphylococcus aureus under stress condition

“…The TA system, which typically comprises a bicistronic operon encoding a stable protein 'toxin' and a labile protein 'antitoxin', have received much attention because of their vital roles in bacterial physiology [5]. As yet, six types of TA systems have been identified based on their mechanism of action and their nature of the antitoxin (RNA or protein), while the toxin is in all of them a protein [6].…”

“…The toxins and antitoxins of all considered bacterial type II TA systems are proteins and are the most prevalent and best-described TAs [6].…”

“…TA systems have been investigated in almost all bacterial species, which are found on plasmids or chromosomes [9]. The number of TA systems varies significantly and can range from none in some species (e.g., in Mycobacterium leprae) to highly abundant in others (e.g., in M. tuberculosis) [6,9].…”