Scientific Reports (Mar 2024)

Comprehensive study reveals phenotypic heterogeneity in Klebsiella pneumoniae species complex isolates

  • Nadia Rodríguez-Medina,
  • Jonathan Rodríguez-Santiago,
  • Alejandro Alvarado-Delgado,
  • Alan Sagal-Prado,
  • Jesús Silva-Sánchez,
  • Miguel A. De la Cruz,
  • Miguel Angel Ares,
  • Margarita Sánchez-Arias,
  • Rayo Morfín-Otero,
  • Rigoberto Hernández-Castro,
  • Patricia Cornejo-Juárez,
  • Emmanuel Jiménez-Villanueva,
  • Domingo Sánchez-Francia,
  • Ulises Garza-Ramos

DOI
https://doi.org/10.1038/s41598-024-55546-z
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 12

Abstract

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Abstract Here, we conducted a comprehensive analysis of 356 Klebsiella pneumoniae species complex (KpSC) isolates that were classified as classical (cl), presumptive hypervirulent (p-hv) and hypermucoviscous-like (hmv-like). Overall, K. pneumoniae (82.3%), K. variicola (2.5%) and K. quasipneumoniae (2.5%) were identified. These isolates comprised 321 cl-KpSC, 7 p-hv-KpSC and 18 hmv-like-KpSC. A large proportion of cl-KpSC isolates were extended-spectrum-β-lactamases (ESBLs)-producers (64.4%) and 3.4% of isolates were colistin-resistant carrying carbapenemase and ESBL genes. All p-hv-KpSC showed an antibiotic susceptible phenotype and hmv-like isolates were found to be ESBL-producers (8/18). Assays for capsule production and capsule-dependent virulence phenotypes and whole-genome sequencing (WGS) were performed in a subset of isolates. Capsule amount differed in all p-hv strains and hmv-like produced higher capsule amounts than cl strains; these variations had important implications in phagocytosis and virulence. Murine sepsis model showed that most cl strains were nonlethal and the hmv-like caused 100% mortality with 3 × 108 CFUs. Unexpectedly, 3/7 (42.9%) of p-hv strains required 108 CFUs to cause 100% mortality (atypical hypervirulent), and 4/7 (57.1%) strains were considered truly hypervirulent (hv). Genomic analyses confirmed the diverse population, including isolates belonging to hv clonal groups (CG) CG23, CG86, CG380 and CG25 (this corresponded to the ST3999 a novel hv clone) and MDR clones such as CG258 and CG147 (ST392) among others. We noted that the hmv-like and hv-ST3999 isolates showed a close phylogenetic relationship with cl-MDR K. pneumoniae. The information collected here is important to understand the evolution of clinically important phenotypes such as hypervirulent and ESBL-producing-hypermucoviscous-like amongst the KpSC in Mexican healthcare settings. Likewise, this study shows that mgrB inactivation is the main mechanism of colistin resistance in K. pneumoniae isolates from Mexico.

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