Prevalence of multidrug-resistant hypervirulent Klebsiella pneumoniae without defined hypervirulent biomarkers in Anhui, China: a new dimension of hypervirulence

Abstract

Klebsiella pneumoniae is an opportunistic pathogen that mainly causes nosocomial infections and hospital-associated pneumonia in elderly and immunocompromised people. However, multidrug-resistant hypervirulent K. pneumoniae (MDR-hvKp) has emerged recently as a serious threat to global health that can infect both immunocompromised and healthy individuals. It is scientifically established that plasmid-mediated regulator of mucoid phenotype genes (rmpA and rmpA2) and other virulence factors (aerobactin and salmochelin) are mainly responsible for this phenotype. In this study, we collected 23 MDR-hvKp isolates and performed molecular typing, whole genome sequencing, comparative genomic analysis, and phenotypic experiments, including the Galleria mellonella infection model, to reveal its genetic and phenotypic features. Meanwhile, we discovered two MDR-hvKp isolates (22122315 and 22091569) that showed a wide range of hypervirulence and hypermucoviscosity without rmpA and rmpA2 and any virulence factors. In phenotypic experiments, isolate 22122315 showed the highest hypervirulence (infection model) with significant mucoviscosity, and conversely, isolate 22091569 exhibited the highest mucoviscosity (string test) with higher virulence compared to control. These two isolates carried carbapenemase (blaKPC − 2), β-lactamase (blaOXA − 1, blaTEM − 1B), extended-spectrum β-lactamase (ESBL) genes (blaCTX − M − 15, blaSHV − 106), outer membrane protein-coding genes (ompA), fimbriae encoding genes (ecpABCDER), and enterobactin coding genes (entAB, fepC). In addition, single nucleotide polymorphism analysis indicated that both isolates, 22122315 and 22091569, were found to have novel mutations in loci FEBNDAKP_03184 (c. 2084A > C, p. Asn695Thr), and EOFMAFIB_02276 (c. 1930C > A, p. Pro644Thr), respectively. Finally, NCBI blast analysis suggested these mutations are located in the wzc of the capsule polysaccharide (cps) region and are responsible for putative tyrosine kinase. This study would be a strong reference for enhancing the current understanding of identifying the MDR-hvKp isolates that lacked both mucoid regulators and virulence factors.

RETRACTED: Drug Resistance and Molecular Characteristics of Carbapenem-Resistant OXA-48-Producing Klebsiella pneumoniae Strains in Hainan, China

“…K. pneumoniae , as a vital human pathogen, represents increasing multidrug-resistance, particularly to third-generation cephalosporins and carbapenems [ 11 ]. Taking into account the mortality and morbidity of patients, medical burden, global drug resistance trends, and other relevant standards, CRKP was undoubtedly considered a key priority pathogen in the priority antibiotic-resistant bacteria list by the World Health Organization (WHO) in 2017 [ 3 , 4 ]. Carbapenem resistance is primarily mediated by the production of carbapenemases (carbapenem hydrolyzing-lactamases), which have been found in KP isolates to fall into three categories: (1) metallo-lactamases or molecular class B lactamases (New Delhi metallo-lactamase/NDM-1, IMP, VIM) that hydrolyze all lactams except monobactams and are inhibited by ethylenediamine tetraacetic acid (EDTA) but not clavulanic acid; (2) serine-lactamases of molecular class A (NMC/IMI, SME, KPC, and GES) that hydrolyze even monobactams are inhibited by clavulanic acid and tazobactam but not by EDTA; (3) molecular class D serine β-lactamases (oxacillinases β-lactamases/OXA-48) that do not hydrolyze monobactams and are poorly inhibited by clavulanic acid and EDTA [ 4 , 5 ].…”

“…Apart from antimicrobial resistance, another worrisome development is related to the evolution of hypervirulent KP (hvKP). hvKP strains, which is usually thought to be attributed to the carriage of a virulence plasmid that harbors two CPS regulator genes (rmpA and rmpA2) and a number of siderophore gene clusters [ 1 , 3 ]. The emergence of hvKP has also become a global concern because it poses a significant constraint on therapeutic strategies in clinics.…”