Early Response of Antimicrobial Resistance and Virulence Genes Expression in Classical, Hypervirulent, and Hybrid hvKp-MDR Klebsiella pneumoniae on Antimicrobial Stress.

Anastasiia D. Fursova,Galina N. Fedyukina,Angelina A. Kislichkina,Tatiana S. Novikova,Irina A. Alexandrova,Mikhail V. Fursov,Nadezhda K. Fursova,Evgenii I. Astashkin,Ivan A. Dyatlov,Olga N. Ershova

doi:10.3390/antibiotics11010007

Abstract

Klebsiella pneumoniae is an increasingly important hospital pathogen. Classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp) are two distinct evolutionary genetic lines. The recently ongoing evolution of K. pneumoniae resulted in the generation of hybrid hvKP-MDR strains. K. pneumoniae distinct isolates (n = 70) belonged to 20 sequence types with the prevalence of ST395 (27.1%), ST23 (18.6%), ST147 (15.7%), and ST86 (7.1%), and 17 capsular types with the predominance of K2 (31.4%), K57 (18.6%), K64 (10.0%), K1 (5.7%) were isolated from patients of the Moscow neurosurgery ICU in 2014–2019. The rate of multi-drug resistant (MDR) and carbapenem-resistant phenotypes were 84.3% and 45.7%, respectively. Whole-genome sequencing of five selected strains belonging to cKp (ST395K47 and ST147K64), hvKp (ST86K2), and hvKp-MDR (ST23K1 and ST23K57) revealed blaSHV, blaTEM, blaCTX, blaOXA-48, and blaNDM beta-lactamase genes; acr, oqx, kpn, kde, and kex efflux genes; and K. pneumoniae virulence genes. Selective pressure of 100 mg/L ampicillin or 10 mg/L ceftriaxone induced changes of expression levels for named genes in the strains belonging to cKp, hvKp, and hybrid hvKp-MDR. Obtained results seem to be important for epidemiologists and clinicians for enhancing knowledge about hospital pathogens.

Highlights

Klebsiella pneumoniae is an increasingly important hospital pathogen causing a wide range of infections including urinary tract infections, pneumonia, bacteremia, and liver abscesses
Non-duplicate 70 K. pneumoniae isolates collected from 62 patients were attributed to specific genetic lines, virulence, and antimicrobial resistance genotypes
Double isolates were studied from one patient in a case of their differences in ST (Patients 19, 32, 36, 46, and 48), K-type (Patient 35), and antimicrobial resistance genes profiles (Patients 4 and 39) (Table S1)

Summary

Introduction

Klebsiella pneumoniae is an increasingly important hospital pathogen causing a wide range of infections including urinary tract infections, pneumonia, bacteremia, and liver abscesses. It can lead to multiple organ failure, or even death [1]. Two different evolutionary genetic lines, classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp), were described and are both global pathogens [2]. Most multidrugresistant (MDR) K. pneumoniae strains belong to particular clones (ST11, ST395, ST147, etc.) producing beta-lactamases in combination with other functional classes of resistance determinants [3]. Hypervirulent K. pneumoniae were attributed to sequence types ST23, ST86, ST65, etc., and capsular types K1, K2, K57, K20, etc. Virulence determinants of hvKp include siderophore systems for iron acquisition, increased capsule production, and the colibactin toxin commonly located on virulence plasmids [5]

Methods

Results

Conclusion