Dataset Information

Unraveling the evolutionary dynamics of toxin-antitoxin systems in diverse genetic lineages of Escherichia coli including the high-risk clonal complexes.

ABSTRACT:

Importance

Large-scale genomic studies of E. coli provide an invaluable opportunity to understand how genomic fine-tuning contributes to the transition of bacterial lifestyle from being commensals to mutualists or pathogens. Within this context, through machine learning-based studies, it appears that TA systems play an important role in the classification of high-risk clonal lineages and could be attributed to their epidemiological success. Due to these profound indications and assumptions, we attempted to provide unique insights into the ordered world of TA systems at the population level by investigating the diversity and evolutionary patterns of TA genes across 19 different STs of E. coli. Further in-depth analysis of ST-specific TA structures and associated genetic coordinates holds the potential to elucidate the functional implications of TA systems in bacterial cell survival and persistence, by and large.

SUBMITTER: Singh A

PROVIDER: S-EPMC10790755 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Unraveling the evolutionary dynamics of toxin-antitoxin systems in diverse genetic lineages of <i>Escherichia coli</i> including the high-risk clonal complexes.

Singh Anuradha A Lankapalli Aditya Kumar AK Mendem Suresh Kumar SK Semmler Torsten T Ahmed Niyaz N

mBio 20231220 1

<h4>Importance</h4>Large-scale genomic studies of <i>E. coli</i> provide an invaluable opportunity to understand how genomic fine-tuning contributes to the transition of bacterial lifestyle from being commensals to mutualists or pathogens. Within this context, through machine learning-based studies, it appears that TA systems play an important role in the classification of high-risk clonal lineages and could be attributed to their epidemiological success. Due to these profound indications and as ...[more]

PMID: 38117088

Similar Datasets

Project description:Toxin-antitoxin (TA) modules containing a Gcn5-related N-acetyltransferase (GNAT) toxin domain regulate bacterial physiology under adverse environmental stresses. Multiple GNAT-ribbon-helix-helix domain (RHH) TA loci have been identified in single bacterial genomes. However, their diversity and interactions are still obscure. Our previous analysis showed that the GNAT toxin of Klebsiella pneumoniae, KacT, introduces antibiotic tolerance and the toxicity of GNAT is neutralized by KacA, an RHH antitoxin. We here present a phylogenetic analysis of GNAT toxins of more than 1,000 GNAT-RHH pairs detected in completely sequenced K. pneumoniae genomes, revealing that the GNAT toxins are diverse and grouped into four distinct clades. Overexpression of GNAT toxins representative of each of the four clades halts the cell growth of K. pneumoniae, while the coexpression of the cognate RHH antitoxin neutralizes GNAT toxicity. We also identify point mutations that inactivate the GNAT toxins. Moreover, we observe a cross-interaction between GNAT-RHH pairs encoded by different replicons, where a chromosomal toxin (KacT2) can be neutralized by its cognate RHH antitoxin (KacA2 on a chromosome) and another antitoxin (KacA3 on a plasmid). Finally, statistical analysis of the distribution of GNAT-RHH loci in K. pneumoniae strains shows pronounced deviation from random distribution within the same clades. Moreover, we also obtain statistically significant correlations between different clades, which we discuss in terms of the experimental results. IMPORTANCE Elucidating the roles of multifaceted GNAT-RHH TA loci is essential for understanding how these TAs interact among themselves. Recently, the reaction mechanisms and structures of several GNAT-RHH pairs have been reported. While bacterial strains can carry multiple GNAT-RHH loci with diverse origins, studies on the possible cross-interactions of these TA pairs are still limited. Here, we find that 1,000 predicted GNAT toxins of K. pneumoniae can be grouped into four distinct clades. The distributions of TA loci within these clades in K. pneumoniae strains are highly nonrandom, with the presence of a single locus of each clade per strain being highly overrepresented. Moreover, the toxicity of a GNAT toxin encoded by a chromosome was alleviated by a noncognate RHH antitoxin on a plasmid. These results might yield a profound understanding of the widespread GNAT-RHH TA pairs and the cross-interactions between noncognate TA pairs located on different replicons.