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Heuristic Mining of Hierarchical Genotypes and Accessory Genome Loci in Bacterial Populations
Published on: December 7, 2021
Genomic Analysis of Hypervirulent Klebsiella pneumoniae ST1-KL122
Yu Yang1,2, Zhien He3,4, Yuanyuan Dai5
1Department of Emergency Intensive Care Unit, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, 230001, Anhui, China.
Background:
Hypervirulent Klebsiella pneumoniae (hvKp) is often characterized by hypervirulence and hypermucoviscosity, traits classically associated with the virulence regulators rmpA and rmpA2. However, some clinically virulent isolates lack these canonical regulators, suggesting the existence of non-canonical pathways driving hypervirulence.
Objective:
This study aimed to investigate the genetic basis of hypervirulence and hypermucoviscosity in clinical K. pneumoniae isolates that lack the rmpA and rmpA2.
Materials And Methods:
A total of 20 clinical isolates were collected. Virulence was assessed using the Galleria mellonella infection model. The hypermucoviscous phenotype was determined using the string test and mucoviscosity assay. Whole-genome sequencing (WGS) and comparative genomic analysis were performed to identify genetic variations, with a particular focus on an ST1-KL122 isolate (1744) that exhibited hypervirulence and hypermucoviscosity despite the absence of rmpA and rmpA2.
Results:
All 20 isolates induced at least 25% mortality in G. mellonella. Most isolates displayed a hypermucoviscous phenotype, except for isolates 2355, 2324, and 1951. WGS confirmed the absence of rmpA and rmpA2 in isolates 2355, 2324, 1951, and the hypermucoviscous isolate 1744. In the hypervirulent and hypermucoviscous ST1-KL122 isolate 1744, comparative genomic analysis identified two nonsynonymous mutations in the wzc gene, which encodes a tyrosine kinase involved in capsular polysaccharide (CPS) export: c.1397A>C (p.Asn466Thr) and c.1721A>T (p.His574Leu).
Conclusions:
Our findings provide evidence that mutations in the wzc suggest a potential non-canonical regulatory mechanism that may drive CPS-mediated hypermucoviscosity and hypervirulence in rmpA/rmpA2-negative hvKp. Further verification in more clinical strains is warranted.
