Impairment of novel non-coding small RNA00203 inhibits biofilm formation and reduces biofilm-specific antibiotic resistance in Acinetobacter baumannii

Shenkutie, Abebe Mekuria; Gebrelibanos, Daniel; Yao, Mianzhi; Bedada Hundie, Gadissa; Chow, Franklin W.N.; Leung, Polly H.M.

doi:10.1016/j.ijantimicag.2023.106889

Cited by 6 publications

(1 citation statement)

References 45 publications

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“…Thus, sRNA is a post-transcriptional regulator of genes involved in important cellular processes, such as bacterial growth, virulence, and drug resistance, and is considered an RNA-based drug target [ 21 , 22 ]. For instance, sRNA00203 is known to induce antibiotic resistance in Acinetobacter baumannii by promoting biofilm formation [ 23 ]. Additionally, sRNA1039 regulates Shigella sonnei sensitivity to ampicillin, gentamicin, and cefuroxime by regulating the expression of the target gene CFA mRNA [ 24 ].…”

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confidence: 99%

sRNA expression profile of KPC-2-producing carbapenem-resistant Klebsiella pneumoniae: Functional role of sRNA51

Bai,

Xie,

Zhang

et al. 2024

PLoS Pathog

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The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has significant challenges to human health and clinical treatment, with KPC-2-producing CRKP being the predominant epidemic strain. Therefore, there is an urgent need to identify new therapeutic targets and strategies. Non-coding small RNA (sRNA) is a post-transcriptional regulator of genes involved in important biological processes in bacteria and represents an emerging therapeutic strategy for antibiotic-resistant bacteria. In this study, we analyzed the transcription profile of KPC-2-producing CRKP using RNA-seq. Of the 4693 known genes detected, the expression of 307 genes was significantly different from that of carbapenem-sensitive Klebsiella pneumoniae (CSKP), including 133 up-regulated and 174 down-regulated genes. Both the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly related to metabolism. In addition, we identified the sRNA expression profile of KPC-2-producing CRKP for the first time and detected 115 sRNAs, including 112 newly discovered sRNAs. Compared to CSKP, 43 sRNAs were differentially expressed in KPC-2-producing CRKP, including 39 up-regulated and 4 down-regulated sRNAs. We chose sRNA51, the most significantly differentially expressed sRNA in KPC-2-producing CRKP, as our research subject. By constructing sRNA51-overexpressing KPC-2-producing CRKP strains, we found that sRNA51 overexpression down-regulated the expression of acrA and alleviated resistance to meropenem and ertapenem in KPC-2-producing CRKP, while overexpression of acrA in sRNA51-overexpressing strains restored the reduction of resistance. Therefore, we speculated that sRNA51 could affect the resistance of KPC-2-producing CRKP by inhibiting acrA expression and affecting the formation of efflux pumps. This provides a new approach for developing antibiotic adjuvants to restore the sensitivity of CRKP.

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