Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/5150
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dc.contributor.authorGoh, Ying-Xianen_US
dc.contributor.authorLi, Peifeien_US
dc.contributor.authorWang, Mengen_US
dc.contributor.authorĐorđević, Markoen_US
dc.contributor.authorTai, Cuien_US
dc.contributor.authorWang, Huien_US
dc.contributor.authorDeng, Zixinen_US
dc.contributor.authorChen, Zhaoyanen_US
dc.contributor.authorOu, Hong-Yuen_US
dc.date.accessioned2022-11-21T12:54:52Z-
dc.date.available2022-11-21T12:54:52Z-
dc.date.issued2022-08-31-
dc.identifier.issn2165-0497-
dc.identifier.urihttps://biore.bio.bg.ac.rs/handle/123456789/5150-
dc.description.abstractToxin-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.en_US
dc.language.isoenen_US
dc.publisherNational Library of Medicineen_US
dc.relation.ispartofMicrobiology spectrumen_US
dc.subjectGNAT and RHHen_US
dc.subjectKlebsiella pneumoniaeen_US
dc.subjectAcetyltransferaseen_US
dc.subjectToxin and antitoxin systemen_US
dc.titleComparative Analysis of Diverse Acetyltransferase-Type Toxin-Antitoxin Loci in Klebsiella pneumoniaeen_US
dc.typeArticleen_US
dc.identifier.doi10.1128/spectrum.00320-22-
dc.description.rankM21en_US
dc.description.impact9.043en_US
dc.description.startpagee00320en_US
dc.description.volume10en_US
dc.description.issue4en_US
item.languageiso639-1en-
item.cerifentitytypePublications-
item.openairetypeArticle-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.author.deptChair of General Physiology and Biophysics-
crisitem.author.orcid0000-0002-2903-3119-
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