Comparative Analysis of Diverse Acetyltransferase-Type Toxin-Antitoxin Loci in Klebsiella pneumoniae

Goh, Ying-Xian; Li, Peifei; Wang, Meng; Djordjevic, M.; Tai, Cui; Wang, Hui; Deng, Zixin; Chen, Zhaoyan; Ou, Hong‐Yu

doi:10.1128/spectrum.00320-22

Cited by 2 publications

(3 citation statements)

References 42 publications

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“…A total of 364, 100, and 2,050 plasmids were classified as ARG-carrying, virulent, and other plasmids, respectively. Of the 2,514 plasmids, 3,164 putative type II TA loci have been predicted [ 34 ]. Kruskal–Wallis one-way ANOVA showed that, overall, virulence plasmids had significantly ( P < 0.001) more TA loci than ARG-carrying and other plasmids ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

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RES-Xre toxin-antitoxin locus knaAT maintains the stability of the virulence plasmid in Klebsiella pneumoniae

Chen,

Goh,

et al. 2024

Emerging Microbes & Infections

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Hypervirulent Klebsiella pneumoniae isolates have been increasingly reported worldwide , especially hypervirulent drug-resistant variants owing to the acquisition of a mobilizable virulence plasmid by a carbapenem-resistant strain. This pLVPK-like mobilizable plasmid encodes various virulence factors; however, information about its genetic stability is lacking. This study aimed to investigate the type II toxin-antitoxin (TA) modules that facilitate the virulence plasmid to remain stable in K. pneumoniae . More than 3,000 TA loci in 2,000 K. pneumoniae plasmids were examined for their relationship with plasmid cargo genes. TA loci from the RES-Xre family were highly correlated with virulence plasmids of hypervirulent K. pneumoniae . Overexpression of the RES toxin KnaT, encoded by the virulence plasmid-carrying RES-Xre locus knaAT, halts the cell growth of K. pneumoniae and E. coli , whereas co-expression of the cognate Xre antitoxin KnaA neutralizes the toxicity of KnaT. knaA and knaT were co-transcribed, representing the characteristics of a type II TA module. The knaAT deletion mutation gradually lost its virulence plasmid in K. pneumoniae, whereas the stability of the plasmid in E. coli was enhanced by adding knaAT , which revealed that the knaAT operon maintained the genetic stability of the large virulence plasmid in K. pneumoniae . String tests and mouse lethality assays subsequently confirmed that a loss of the virulence plasmid resulted in reduced pathogenicity of K. pneumoniae . These findings provide important insights into the role of the RES-Xre TA pair in stabilizing virulence plasmids and disseminating virulence genes in K. pneumonia e.

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Section: Resultsmentioning

confidence: 99%

“…Among 3,164 putative type II TA loci predicted in the plasmids, 6% ( n = 176) were RES-Xre, which ranked it as the fifth most common type II TA family in the K. pneumoniae’s plasmids[ 34 ]. The predominant sequence types (STs) of K. pneumoniae carrying the virulence plasmids were ST11 ( n = 32) and ST23 ( n = 20) (Table S2).…”

Section: Resultsmentioning

confidence: 99%

RES-Xre toxin-antitoxin locus knaAT maintains the stability of the virulence plasmid in Klebsiella pneumoniae

Chen,

Goh,

et al. 2024

Emerging Microbes & Infections

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“…Additionally, in some isolates of E. coli , plasmid-encoded AtaT toxin of the ataRT toxin-antitoxin cassette was inhibited by chromosomal AtaR antitoxin [ 80 ]. Moreover, Gog and co-workers observed cross-interactions between the KacA3 antidote located on a plasmid and chromosomal KacT2 toxin in Klebsiella pneumoniae [ 121 ]. Weak interactions were also identified between the Kid toxin of the kis-kid locus derived from the R1 plasmid and its chromosomal homolog—the E. coli MazE antitoxin [ 105 ].…”

Section: Modes Of the Toxin-antitoxin System Cross-talkmentioning

confidence: 99%

Bacterial Toxin-Antitoxin Systems’ Cross-Interactions—Implications for Practical Use in Medicine and Biotechnology

Boss

Kędzierska

2023

Toxins

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Toxin-antitoxin (TA) systems are widely present in bacterial genomes. They consist of stable toxins and unstable antitoxins that are classified into distinct groups based on their structure and biological activity. TA systems are mostly related to mobile genetic elements and can be easily acquired through horizontal gene transfer. The ubiquity of different homologous and non-homologous TA systems within a single bacterial genome raises questions about their potential cross-interactions. Unspecific cross-talk between toxins and antitoxins of non-cognate modules may unbalance the ratio of the interacting partners and cause an increase in the free toxin level, which can be deleterious to the cell. Moreover, TA systems can be involved in broadly understood molecular networks as transcriptional regulators of other genes’ expression or modulators of cellular mRNA stability. In nature, multiple copies of highly similar or identical TA systems are rather infrequent and probably represent a transition stage during evolution to complete insulation or decay of one of them. Nevertheless, several types of cross-interactions have been described in the literature to date. This implies a question of the possibility and consequences of the TA system cross-interactions, especially in the context of the practical application of the TA-based biotechnological and medical strategies, in which such TAs will be used outside their natural context, will be artificially introduced and induced in the new hosts. Thus, in this review, we discuss the prospective challenges of system cross-talks in the safety and effectiveness of TA system usage.

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Comparative Analysis of Diverse Acetyltransferase-Type Toxin-Antitoxin Loci in Klebsiella pneumoniae

Abstract: 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.

Cited by 2 publications

References 42 publications

RES-Xre toxin-antitoxin locus knaAT maintains the stability of the virulence plasmid in Klebsiella pneumoniae

RES-Xre toxin-antitoxin locus knaAT maintains the stability of the virulence plasmid in Klebsiella pneumoniae

Bacterial Toxin-Antitoxin Systems’ Cross-Interactions—Implications for Practical Use in Medicine and Biotechnology

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