Dataset Information

Hypervirulence Markers Among Non-ST11 Strains of Carbapenem- and Multidrug-Resistant Klebsiella pneumoniae Isolated From Patients With Bloodstream Infections.

ABSTRACT: Multidrug-resistant Klebsiella pneumoniae and hypervirulent K. pneumoniae (hvKP) have traditionally been considered two individual populations; however, strains displaying both phenotypes have emerged during the recent decade. Understanding the genotypic and phenotypic basis of the convergence could be of clinical importance. In this study, we aimed to evaluate the pathogenicity associated with different combinations of genotypes (i.e., sequence types, virulence factors, and capsular serotypes) and phenotypes (i.e., hypermucoviscosity and drug susceptibility) in K. pneumoniae. A total of 11 K. pneumoniae isolates causing bloodstream infections were included in the study, and they were assigned to seven STs (ST23, ST15, ST268, ST660, ST86, ST65, and ST1660) and carried various K-loci (KL1, KL2, KL16, KL20, and KL24). Hypermucoviscosity was observed for six isolates. bla KPC-2 was detected in six carbapenem-resistant isolates, and the remaining ones were either multidrug-resistant or resistant to two types of antibiotics. Aerobactin- and yersiniabactin-encoding genes were detected in all isolates. Although rmpA2 was detected in all isolates, most contained frameshift mutations (82%). Genes encoding salmochelin, RmpA, and PEG344 were detected in seven isolates. Colibactin-encoding genes were carried by six isolates. Discrepancies among measured virulence in Galleria mellonella and the serum-killing assay, and genotypes and phenotypes were detected. The results illustrate the complexity and difficulty with the current knowledge of hypervirulence to predict the phenotype by using genetic and phenotypic markers. Additionally, the emergence of carbapenem resistance in two isolates of KPC-2-producing hvKP of different sequence types emphasizes the urgency with which reliable clinical diagnostics for hvKP is needed.

SUBMITTER: Shen P

PROVIDER: S-EPMC7314899 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hypervirulence Markers Among Non-ST11 Strains of Carbapenem- and Multidrug-Resistant Klebsiella pneumoniae Isolated From Patients With Bloodstream Infections.

Shen Ping P Berglund Björn B Chen Yong Y Zhou Yanzi Y Xiao Tingting T Xiao Yonghong Y Zhou Kai K

Frontiers in microbiology 20200618

Multidrug-resistant Klebsiella pneumoniae and hypervirulent K. pneumoniae (hvKP) have traditionally been considered two individual populations; however, strains displaying both phenotypes have emerged during the recent decade. Understanding the genotypic and phenotypic basis of the convergence could be of clinical importance. In this study, we aimed to evaluate the pathogenicity associated with different combinations of genotypes (i.e., sequence types, virulence factors, and capsul ...[more]

PMID: 32625176

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Project description:Klebsiella pneumoniae is a major cause of neonatal sepsis. Hypervirulent Klebsiella pneumoniae (hvKP) that cause invasive infections and/or carbapenem-resistant hvKP (CR-hvKP) limit therapeutic options. Such strains causing neonatal sepsis have rarely been studied. Characterization of neonatal septicemic hvKP/CR-hvKP strains in terms of resistance and virulence was carried out. Antibiotic susceptibility, molecular characterization, evaluation of clonality, in vitro virulence, and transmissibility of carbapenemase genes were evaluated. Whole-genome sequencing (WGS) and mouse lethality assays were performed on strains harboring pLVPK-associated markers. About one-fourth (26%, 28/107) of the studied strains, leading to mortality in 39% (11/28) of the infected neonates, were categorized as hvKP. hvKP-K2 was the prevalent pathotype (64.2%, 18/28), but K54 and K57 were also identified. Most strains were clonally diverse belonging to 12 sequence types, of which ST14 was most common. Majority of hvKPs possessed virulence determinants, strong biofilm-forming, and high serum resistance ability. Nine hvKPs were carbapenem-resistant, harboring blaNDM-1/blaNDM-5 on conjugative plasmids of different replicon types. Two NDM-1-producing high-risk clones, ST11 and ST15, had pLVPK-associated markers (rmpA, rmpA2, iroBCDEN, iucABCDiutA, and peg-344), of which one co-transferred the markers along with blaNDM-1. The 2 strains revealed high inter-genomic resemblance with the other hvKP reference genomes, and were lethal in mouse model. To the best of our knowledge, this study is the first to report on the NDM-1-producing hvKP ST11-K2 and ST15-K54 strains causing fatal neonatal sepsis. The presence of pLVPK-associated markers and blaNDM-1 in high-risk clones, and the co-transmission of these genes via conjugation calls for surveillance of these strains. IMPORTANCE Klebsiella pneumoniae is a leading cause of sepsis in newborns and adults. Among the 2 major pathotypes of K. pneumoniae, classical (cKP) and hypervirulent (hvKP), hvKP causes community-acquired severe fatal invasive infections in even healthy individuals, as it possesses several virulence factors. The lack of comprehensive studies on neonatal septicemic hvKPs prompted this work. Nearly 26% diverse hvKP strains were recovered possessing several resistance and virulence determinants. The majority of them exhibited strong biofilm-forming and high serum resistance ability. Nine of these strains were also carbapenem (last-resort antibiotic)-resistant, of which 2 high-risk clones (ST11-K2 and ST15-K54) harbored markers (pLVPK) noted for their virulence, and were lethal in the mouse model. Genome-level characterization of the high-risk clones showed resemblance with the other hvKP reference genomes. The presence of transmissible carbapenem-resistant gene, blaNDM, along with pLVPK-markers calls for vigilance, as most clinical microbiology laboratories do not test for them.

Project description:Klebsiella pneumoniae, a notorious pathogen for opportunistic health care-associated infections, represents increasing multidrug resistance, particularly to carbapenems. OXA-232 carbapenemase, as a variant of OXA-48, has been increasingly reported worldwide. ST231, an epidemic, multidrug resistant (MDR) K. pneumoniae clone in south and southeast Asia, has been found in other regions, including Europe. In the study, five OXA-232 carbapenemase-producing Klebsiella pneumoniae isolates, four of which belong to sequence type 231 (ST231) and one of which belongs to ST15, were isolated from two hospitals in China. All isolates displayed a MDR phenotype, being susceptible to only polymyxin B and colistin, and the blaOXA-232 gene was located on a ColKP3-type nonconjugative plasmid of 6.1 kb. A phylogenetic analysis of the global ST231 K. pneumoniae isolates (n = 231) suggested that the four ST231 isolates from this study gathered with strains from south Asia (especially India), indicating that the emerging Chinese ST231 clone was more closely related to south Asia isolates and might have spread from south Asia, where ST231 was a successful epidemic clone. Virulence assays suggested that the four ST231 strains were not highly virulent, as they displayed significantly lower virulence potential, compared with a ST23 K1 hypervirulent isolate in a G. mellonella infection and in mouse intraperitoneal infection models, although three ST231 strains harbored a plasmid-borne aerobactin-encoding iuc gene cluster. This is the first report of ST231 K. pneumoniae clinical strains bearing blaOXA-232 in China, and it highlights the emergence of the ST231 clone causing bloodstream infections in a health care setting as well as calls attention to the transmission of this emerging clone in China. IMPORTANCE OXA-232 carbapenemase, being a vital resistance mechanism against carbapenems, has recently been increasingly reported. In China, the identified OXA-232-producing K. pneumoniae isolates almost belonged to ST15 and were not hypervirulent, despite harboring a virulence plasmid. Here, we report the first occurrence in China of a MDR OXA-232-producing K. pneumoniae ST231 clone that is an epidemic ST type in south and southeast Asia. A phylogenetic analysis indicated that this emerging Chinese ST231 clone was more closely related to Indian isolates. The occurrence of this clone may have been driven through the transnational importation of Indian ST231 K. pneumoniae clones. Moreover, this study is the first to assess the virulence potential of ST231 clones that have never been estimated in previous studies. While the high burden of MDR K. pneumoniae is concerning, genomic surveillance can shed light on the transmission chains of novel MDR clones, and active surveillance should be enforced to restrict the spread of MDR isolates.

Dataset Information

Hypervirulence Markers Among Non-ST11 Strains of Carbapenem- and Multidrug-Resistant Klebsiella pneumoniae Isolated From Patients With Bloodstream Infections.

Publications

Hypervirulence Markers Among Non-ST11 Strains of Carbapenem- and Multidrug-Resistant <i>Klebsiella pneumoniae</i> Isolated From Patients With Bloodstream Infections.

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