Acquisition of regulator on virulence plasmid of hypervirulent Klebsiella allows bacterial lifestyle switch in response to iron

作者：Wilson H. W. Chu, Yi Han Tan, S.Y. Tan, Yahua Chen, Melvin Yong, David Chien Lye, Shirin Kalimuddin, Sophia Archuleta, Yunn‐Hwen Gan · 发表于：mBio · 年份：2023 · DOI：10.1128/mbio.01297-23 · 被引用次数：35 · 研究领域：Antibiotic Resistance in Bacteria、Vibrio bacteria research studies、Bacterial Genetics and Biotechnology

ABSTRACT Hypervirulent Klebsiella pneumoniae causes liver abscess and potentially devastating metastatic complications. The majority of Klebsiella -induced liver abscess are caused by the CG23-I sublineage of hypervirulent Klebsiella pneumoniae . This and some other lineages possess a >200-kb virulence plasmid. We discovered a novel protein IroP nestled in the virulence plasmid-encoded salmochelin operon that cross-regulates and suppresses the promoter activity of chromosomal type 3 fimbriae (T3F) gene transcription. IroP is itself repressed by iron through the ferric uptake regulator. Iron-rich conditions increase T3F and suppress capsule mucoviscosity, leading to biofilm formation and cell adhesion. Conversely, iron-poor conditions cause a transcriptional switch to hypermucoid capsule production and T3F repression. The likely acquisition of iroP on mobile genetic elements and successful adaptive integration into the genetic circuitry of a major lineage of hypervirulent K. pneumoniae reveal a powerful example of plasmid chromosomal cross talk that confers an evolutionary advantage. Our discovery also addresses the conundrum of how the hypermucoid capsule that impedes adhesion could be regulated to facilitate biofilm formation and colonization. The acquired ability of the bacteria to alternate between a state favoring dissemination and one that favors colonization in response to iron availability through transcriptional regulation offers novel insights into the evolutionar...