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Klebsiella species: Taxonomy, hypervirulence and multidrug resistance.

ABSTRACT: Members of the genus Klebsiella have rapidly evolved within the past decade, generating organisms that simultaneously exhibit both multidrug resistance and hypervirulence (MDR-hv) phenotypes; such organisms are associated with severe hospital- and community-acquired infections. Carbapenem-resistant infections with unknown optimal treatment regime were of particular concern among the MDR-hv Klebsiella strains. Recent studies have revealed the molecular features and the mobile resistance elements they harbour, allowing identification of genetic loci responsible for transmission, stable inheritance, and expression of mobile resistance or virulence-encoding elements that confer the new phenotypic characteristics of MDR-hv Klebsiella spp. Here, we provide a comprehensive review on the taxonomic position, species composition and different phylotypes of Klebsiella spp., describing the diversity and worldwide distribution of the MDR-hv clones, the genetic mutation and horizontal gene transfer events that drive the evolution of such clones, and the potential impact of MDR-hv infections on human health.

SUBMITTER: Dong N

PROVIDER: S-EPMC9010751 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Klebsiella species: Taxonomy, hypervirulence and multidrug resistance.

Dong Ning N Yang Xuemei X Chan Edward Wai-Chi EW Zhang Rong R Chen Sheng S

EBioMedicine 20220408

Members of the genus Klebsiella have rapidly evolved within the past decade, generating organisms that simultaneously exhibit both multidrug resistance and hypervirulence (MDR-hv) phenotypes; such organisms are associated with severe hospital- and community-acquired infections. Carbapenem-resistant infections with unknown optimal treatment regime were of particular concern among the MDR-hv Klebsiella strains. Recent studies have revealed the molecular features and the mobile resistance elements ...[more]

PMID: 35405387

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Project description:The emergence of plasmids coharboring hypervirulence (Hv) and multidrug resistance (MDR) genes has further accelerated the spread of MDR-Hv Klebsiella pneumoniae (MDR-HvKP) strains, having a severe impact on public health. Here, we report an MDR-Hv superplasmid coharboring hypervirulence and MDR genes and the detailed characterization of its genetic and phenotypic features. This plasmid was identified in an ST11 (sequence type 11)-K64 carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) strain, SZS128, which was responsible for a bloodstream infection in a 21-year-old female. Susceptibility testing showed that SZS128 was resistant to amikacin, levofloxacin, and almost all of the β-lactams examined. SZS128 showed high virulence in a Galleria mellonella survival assay and a mouse intraperitoneal infection model. Genomic analysis showed that SZS128 not only possessed a KPC plasmid (pSZS128-KPC) but also carried a superplasmid (pSZS128-Hv-MDR) coharboring hypervirulence and MDR genes and possessing complete conjugative regions. Conjugation and transformation assays confirmed the potential for horizontal transfer and the high stability (retention rate of >95%) of the pSZS128-Hv-MDR superplasmid. Furthermore, growth curve assessment confirmed that there was no increase in the fitness cost in the presence of pSZS128-Hv-MDR. Therefore, we define a superplasmid as a plasmid fulfilling all the following criteria: (i) a single plasmid that coharbors hypervirulence and MDR genes, (ii) a plasmid that harbors complete conjugative elements that guarantee self-transmissibility, (iii) a plasmid that is stable and conserved, and (iv) a plasmid with no fitness cost to the host strain. The emergence of this kind of superplasmid could represent a serious threat to public health, and urgent control measures must be implemented. IMPORTANCE This self-transmissible superplasmid, which simultaneously carries hypervirulence and MDR genes, greatly enhances the challenges to clinical prevention and control and anti-infection treatment. Thus, active surveillance of this type of superplasmid is needed to prevent these efficient resistance/virulence plasmids from disseminating in hospital settings. Our findings provide a reference for defining the term "superplasmid" and emphasize the importance of raising public awareness of the rapid dissemination of this self-transmissible superplasmid and the consistent emergence of MDR-HvKP strains.

Project description: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.

Project description:Klebsiella pneumoniae complex is an increasingly important bacterial pathogen that is capable of causing severe organs and life-threatening disease. This study aimed to investigate the multidrug resistance, phylogroups, molecular characterization, and hypervirulence-associated determinants of the complex, which were isolated from clinical diseased dogs and cats. A total of 35 K. pneumoniae complex (2.3%; 95% confidence interval, 1.6-3.2) isolates were identified from 1,500 samples, all of which were collected randomly from veterinary hospitals in the 12 regions across China. Antimicrobial susceptibility testing showed that isolates were extremely resistant to amoxicillin-clavulanate (82.9%) and trimethoprim-sulfamethoxazole (77.1%). The rate of multidrug-resistant reached an astonishing 82.9% and found a carbapenemase-producing strain carrying IncX3-bla NDM-5 derived a cat from Zhejiang. The prevalence rates of extended-spectrum β-lactamase gene bla CTX-M and plasmid-mediated quinolone resistance gene aac(6')Ib-cr were 51.4% and 45.7%, respectively. The resistance gene aph(3')-Ia of isolates from cats was more significantly (p < 0.05) prevalent than that from dogs. Likewise, K. pneumoniae complex harbored hypervirulence-associated genes ybt (11.4%), iuc (5.7%), and iroB (2.9%). Three (8.6%) of the 35 isolates were determined as hypermucoviscous by the string test. Lipopolysaccharide serotype O1v2 had the highest percentage of 25.7%, but capsular serotypes presented diversity distribution among the isolates. The core-genome phylogenetic tree demonstrated most of the isolates belonged to the KpI phylogroup (91.4%). Multilocus sequence typing analysis identified 25 different STs; ST15 and ST37 were the most abundant accounting for isolates, followed by ST307, ST656, ST1408, and ST4566. In addition, the prevalence of IncFIB-type plasmid for cat isolates was significantly higher (p < 0.05) than that for dogs. Sequences of IncX3 in bla NDM-5-positive strain contained regions showing >99% nucleotide sequence identity to the reference plasmid pNDM-MGR194 from the human.

Project description:BackgroundKlebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired "hypervirulent" strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide.MethodsWe conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool.ResultsK. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae.ConclusionsK. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance-reporting full molecular profiles including STs, AMR, virulence and serotype locus information-can help standardise comparisons between sites and identify regional differences in pathogen populations.

Dataset Information

Klebsiella species: Taxonomy, hypervirulence and multidrug resistance.

Publications

Klebsiella species: Taxonomy, hypervirulence and multidrug resistance.

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