TadA-mediated A-to-I mRNA editing rewires redox metabolism to promote dominance of epidemic Klebsiella pneumoniae clones

• 成果类型: Article
• 署名作者: Wu, Xingyu; Jin, Longyang; Wang, Qi; Wang, Ruobing; Li, Bowen; Jiang, Chongyang; Song, Kaiwen; Chen, Long; Yin, Guankun; Chen, Fengning; Liu, Xiaoyun; Wang, Hui
• 署名单位: Peking University; Peking University; Peking University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2536397123
• 发表日期: 2026-06-09
• 页码: e2536397123
• 关键词: A-to-I mRNA editing; carbapenem-resistant Klebsiella pneumoniae; PncR transcription factor; redox metabolism; TadA; noncoding rnas; complex; FAMILY; DCUR

摘要

Dominant carbapenem-resistant Klebsiella pneumoniae (CRKP) clones have markedly intensified the burden of invasive infections while severely restricting treatment options. Although genomic determinants of these high-risk lineages are well characterized, adaptive regulatory mechanisms beyond fixed DNA variation remain poorly understood. Here we systematically map the adenosine-to-inosine (A-to-I) mRNA editing landscape in CRKP and reveal that clinically dominant lineages possess a constrained and clone-specific landscape of RNA editing. We identify PncR (a previously uncharacterized AraC/XylS family transcription factor) and the response regulator DcuR as prominent A-to-I editing targets enriched in high-risk clones. Editing of these regulators reshapes redox and metabolic programs, thereby increasing tolerance to oxidative stress associated with innate immune attack. These results support a model in which stress-responsive RNA editing promotes stress adaptation specifically in high-risk CRKP clones. Furthermore, we demonstrate that the tRNA deaminase TadA is the sole A-to-I editing enzyme in K. pneumoniae, and that its abundance determines both the extent and diversity of mRNA editing. These findings establish TadA-driven A-to-I editing as a selectable, posttranscriptional regulatory layer that reshapes bacterial metabolism and promotes the success of high-risk CRKP lineages, highlighting this axis as a potential target for therapeutic intervention.