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Characteristics of Hypervirulent Klebsiella pneumoniae: Does Low Expression of rmpA Contribute to the Absence of Hypervirulence?

ABSTRACT: Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) has been increasingly reported and is now recognized as a significant threat to public health; however, characterization of MDR-hvKP has not been systematically investigated. In the present study, 124 of 428 (28.92%) K. pneumoniae clinical isolates collected from January 2010 to December 2016 were identified with aerobactin and defined as hvKP; these included 94 non-MDR-KP, 20 extended-spectrum ?-lactamase-producing K. pneumoniae (ESBL-KP), and 10 carbapenem-resistant K. pneumoniae (CR-KP) isolates. The remaining 304 isolates without presence of virulence factor aerobactin were defined as classic K. pneumoniae (cKP). The antimicrobial resistance rate of cKP was significantly higher than that of the hvKP isolates in the non-MDR-KP group, but showed no significant differences in the ESBL-KP and CR-KP groups. The detection frequencies of capsular serotype K1 (magA), hypermucoviscosity, sequence type 23 (ST23), and the virulence gene rmpA were significantly higher in the hvKP than cKP isolates in all three groups (P < 0.05). Most of the hypervirulent ESBL-KP and CR-KP isolates were K non-typeable (16/30) and harbored at least one gene for virulence (26/30). The hypervirulent ESBL-KP isolates primarily carried bla CTX-M (12/20, 60%) genes, and the hypervirulent CR-KP isolates mainly carried bla NDM- 1 (8/10, 80%) genes. Moreover, three hypervirulent ESBL-KP and two hypervirulent CR-KP isolates showed resistance to tigecycline but were sensitive to colistin. The transcriptional levels of rmpA in cKP were much lower than that in hvKP isolates in all three groups. Furthermore, overexpression of rmpA in the rmpA-low-expression cKP isolates could enhance bacterial virulence in the mouse infection experiment. In conclusion, our data suggest that the capsular serotype K1 (magA), rmpA, hypermucoviscosity, and ST23 were strongly associated with hvKP in non-MDR-KP, ESBL-KP, and CR-KP groups, and low rmpA expression levels contributed to the absence of hypervirulent phenotype.

SUBMITTER: Lin ZW

PROVIDER: S-EPMC7090111 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Characteristics of Hypervirulent Klebsiella pneumoniae: Does Low Expression of rmpA Contribute to the Absence of Hypervirulence?

Lin Zhi-Wei ZW Zheng Jin-Xin JX Bai Bing B Xu Guang-Jian GJ Lin Fo-Jun FJ Chen Zhong Z Sun Xiang X Qu Di D Yu Zhi-Jian ZJ Deng Qi-Wen QW

Frontiers in microbiology 20200317

Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) has been increasingly reported and is now recognized as a significant threat to public health; however, characterization of MDR-hvKP has not been systematically investigated. In the present study, 124 of 428 (28.92%) K. pneumoniae clinical isolates collected from January 2010 to December 2016 were identified with aerobactin and defined as hvKP; these included 94 non-MDR-KP, 20 extended-spectrum β-lactamase-producing ...[more]

PMID: 32256482

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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:BackgroundCarbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is gradually becoming the dominant nosocomial pathogens in the healthcare setting.MethodsA retrospective study was conducted on patients with CR-KP from July 2021 to May 2022 in a teaching hospital. We identified bacterial isolates, collected the clinical data, and performed antimicrobial susceptibility testing, hypermucoviscosity string test, antimicrobial and virulence-associated genotype, as well as multi-locus sequence typing. CR-hvKP was defined as the presence of some combination of rmpA and/or rmpA2 with iucA, iroB, or peg-344. SPSS was used for data analysis. Univariate logistic regression analyses were used for risk factor and all statistically significant variables were included in the multivariate model. Statistical significance was taken to be P < 0.05.ResultsA total of 69 non-duplicated CR-KP isolates were collected, 27 of which were CR-hvKP. Out of the 69 CR-KP strains under investigation, they were distributed across 14 distinct sequence types (STs), wherein ST11 exhibited the highest prevalence, constituting 65.2% (45/69) of the overall isolates. The principal carbapenemase genes identified encompassed blakpc-2, blaNDM-1, and blaOXA-48, with blakpc-2 prevailing as the predominant type, accounting for 73.9% (51/69). A total of 69 CR-KP strains showed high resistance to common clinical antibiotics, with the exception of ceftazidime/avibactam. The ST11 (P = 0.040), ST65 (P = 0.030) and blakpc-2 ST11 clones (P = 0.010) were found to be highly related to hvKp. Regarding the host, tracheal intubation (P = 0.008), intracranial infection (P = 0.020) and neutrophil count (P = 0.049) were significantly higher in the patients with CR-hvKP. Multivariate analysis showed tracheal intubation to be an independent risk factor for CR-hvKP infection (P = 0.030, OR = 4.131). According to the clinical data we collected, tracheal intubation was performed mainly in the elderly with severe underlying diseases, which implied that CR-hvKP has become prevalent among elderly patients with comorbidities.ConclusionsThe prevalence of CR-hvKP may be higher than expected in the healthcare setting. CR-hvKP is gradually becoming the dominant nosocomial pathogen, and its prevalence and treatment will be a major challenge. It is essential to enhance clinical awareness and management of CR-hvKP infection.

Project description:UnlabelledHighly invasive, community-acquired Klebsiella pneumoniae infections have recently emerged, resulting in pyogenic liver abscesses. These infections are caused by hypervirulent K. pneumoniae (hvKP) isolates primarily of capsule serotype K1 or K2. Hypervirulent K1 isolates belong to clonal complex 23 (CC23), indicating that this clonal lineage has a specific genetic background conferring hypervirulence. Here, we apply whole-genome sequencing to a collection of K. pneumoniae isolates to characterize the phylogenetic background of hvKP isolates with an emphasis on CC23. Most of the hvKP isolates belonged to CC23 and grouped into a distinct monophyletic clade, revealing that CC23 is a unique clonal lineage, clearly distinct from nonhypervirulent strains. Separate phylogenetic analyses of the CC23 isolates indicated that the CC23 lineage evolved recently by clonal expansion from a single common ancestor. Limited grouping according to geographical origin was observed, suggesting that CC23 has spread globally through multiple international transmissions. Conversely, hypervirulent K2 strains clustered in genetically unrelated groups. Strikingly, homologues of a large virulence plasmid were detected in all hvKP clonal lineages, indicating a key role in K. pneumoniae hypervirulence. The plasmid encodes two siderophores, aerobactin and salmochelin, and RmpA (regulator of the mucoid phenotype); all these factors were found to be restricted to hvKP isolates. Genomic comparisons revealed additional factors specifically associated with CC23. These included a distinct variant of a genomic island encoding yersiniabactin, colibactin, and microcin E492. Furthermore, additional novel genomic regions unique to CC23 were revealed which may also be involved in the increased virulence of this important clonal lineage.ImportanceDuring the last 3 decades, hypervirulent Klebsiella pneumoniae (hvKP) isolates have emerged, causing severe community-acquired infections primarily in the form of pyogenic liver abscesses. This syndrome has so far primarily been found in Southeast Asia, but increasing numbers of cases are being reported worldwide, indicating that the syndrome is turning into a globally emerging disease. We applied whole-genome sequencing to a collection of K. pneumoniae clinical isolates to reveal the phylogenetic background of hvKP and to identify genetic factors associated with the increased virulence. The hvKP isolates primarily belonged to clonal complex 23 (CC23), and this clonal lineage was revealed to be clearly distinct from nonhypervirulent strains. A specific virulence plasmid was found to be associated with hypervirulence, and novel genetic determinants uniquely associated with CC23 were identified. Our findings extend the understanding of the genetic background of the emergence of hvKP clones.

Dataset Information

Characteristics of Hypervirulent Klebsiella pneumoniae: Does Low Expression of rmpA Contribute to the Absence of Hypervirulence?

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Characteristics of Hypervirulent <i>Klebsiella pneumoniae</i>: Does Low Expression of <i>rmpA</i> Contribute to the Absence of Hypervirulence?

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