An Outbreak of Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae in an Intensive Care Unit of a Major Teaching Hospital in Wenzhou, China

Zhao, Yajie; Zhang, Xiucai; Torres, Von Vergel L.; Liu, Haiyang; Rocker, Andrea; Zhang, Yizhi; Wang, Jiawei; Chen, Lijiang; Bi, Wenzi; Lin, Jie; Strugnell, Richard A.; Zhang, Siqin; Lithgow, Trevor; Zhou, Tieli; Cao, Jianming

doi:10.3389/fpubh.2019.00229

Cited by 68 publications

(65 citation statements)

References 68 publications

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“…To date, HMV has primarily been associated with hv K1 and K2 strains, but more than 130 capsule types of K. pneumoniae have been identified ( 44 ). Of significant concern is the number of recent reports of strains with both multidrug resistance and hv-associated genes, including rmpA (and quite likely rmpD and rmpC ) ( 18 – 23 ). These strains are genetically quite distinct (including capsule type) from the hvKp that have been circulating, and it is not known to what degree acquisition of the rmpADC locus will impact HMV and virulence of these strains.…”

Section: Discussionmentioning

confidence: 99%

“…That these genetic entities can be horizontally transferred suggests there is an increased risk of strains acquiring both hypervirulence and multidrug resistance ( 16 , 17 ). Alarmingly, there have been recent reports of extensively resistant hypervirulent K. pneumoniae ( 18 , 19 ), and multiple strains where both hv-associated genes and antimicrobial resistance genes were present on the same mobile vector ( 20 – 23 ). These reports of convergence of hypervirulence and antimicrobial resistance in the same strain have heightened the need to better understand how hypervirulence genes interface with a strain’s genetic background to confer hypervirulent phenotypes.…”

Section: Introductionmentioning

confidence: 99%

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The Small Protein RmpD Drives Hypermucoviscosity in Klebsiella pneumoniae

Walker

Treat

Sepúlveda

et al. 2020

mBio

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Klebsiella pneumoniae has a remarkable ability to cause a wide range of human diseases. It is divided into two broad classes: classical strains that are a notable problem in health care settings due to multidrug resistance, and hypervirulent (hv) strains that are historically drug sensitive but able to establish disease in immunocompetent hosts. Alarmingly, there has been an increased frequency of clinical isolates that have both drug resistance and hv-associated genes. One such gene, rmpA, encodes a transcriptional regulator required for maximal capsule (cps) gene expression and confers hypermucoviscosity (HMV). This link has resulted in the assumption that HMV is caused by elevated capsule production. However, we recently reported a new cps regulator, RmpC, and ΔrmpC mutants have reduced cps expression but retain HMV, suggesting that capsule production and HMV may be separable traits. Here, we report the identification of a small protein, RmpD, that is essential for HMV but does not impact capsule. RmpD is 58 residues with a putative N-terminal transmembrane domain and highly positively charged C-terminal half, and it is conserved among other hv K. pneumoniae strains. Expression of rmpD in trans complements both ΔrmpD and ΔrmpA mutants for HMV, suggesting that RmpD is the key driver of this phenotype. The rmpD gene is located between rmpA and rmpC, within an operon regulated by RmpA. These data, combined with our previous work, suggest a model in which the RmpA-associated phenotypes are largely due to RmpA activating the expression of rmpD to produce HMV and rmpC to stimulate cps expression. IMPORTANCE Capsule is a critical virulence factor in Klebsiella pneumoniae, in both antibiotic-resistant classical strains and hypervirulent strains. Hypervirulent strains usually have a hypermucoviscosity (HMV) phenotype that contributes to their heightened virulence capacity, but the production of HMV is not understood. The transcriptional regulator RmpA is required for HMV and also activates capsule gene expression, leading to the assumption that HMV is caused by hyperproduction of capsule. We have identified a new gene (rmpD) required for HMV but not for capsule production. This distinction between HMV and capsule production will promote a better understanding of the mechanisms of hypervirulence, which is in great need given the alarming increase in clinical isolates with both drug resistance and hypervirulence traits.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Small Protein RmpD Drives Hypermucoviscosity in Klebsiella pneumoniae

Walker

Treat

Sepúlveda

et al. 2020

mBio

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“…Additionally, B14 contained three virulence genes, which included kfuBC , uge , and fim . ST11 is the major sequence type of hypervirulent carbapenem-resistant K. pneumoniae from Asia, especially China ( Zhao et al, 2019 ). Therefore, it is speculated that B14 has certain virulence traits.…”

Section: Discussionmentioning

confidence: 99%

Genotypic and Phenotypic Characterization of blaNDM–7-Harboring IncX3 Plasmid in a ST11 Klebsiella pneumoniae Isolated From a Pediatric Patient in China

et al. 2020

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NDM-7, a variant of New Delhi metallo-beta-lactamases (NDM), has the highest carbapenem-hydrolyzing activity. NDM-7-producing enterobacteria have been reported in many countries. In this study, we reported NDM-7 production in ST11 Klebsiella pneumoniae isolated from a boy hospitalized in the pediatric intensive care unit of a teaching hospital in China. The isolate exhibited resistance to β-lactam antimicrobials, quinolones, and trimethoprim/sulfamethoxazole, and it harbored bla NDM– 7 , bla CTX–M– 15 , qnrA , qnrB , and qnrS . The serotype of the isolated K. pneumoniae was assigned as K1, and it contained three virulence genes, including kfuBC , uge , and fim . The bla NDM– 7 gene was located on a conjugative IncX3 plasmid designated as pB14NDM-7. This plasmid was fully sequenced and compared with the available bla NDM– 7 -harboring IncX3 plasmids. pB14NDM-7 contained a conserved genetic context of ISkox3-umuD-IS26-ΔTn125 -IS5- ΔTn125-IS3000-ΔTn2 . pB14NDM-7 showed 99% nucleotide identity and the same genetic context with three bla NDM– 7 -harboring IncX3 plasmids obtained from Escherichia coli in China. Our results indicate that IncX3 plasmid may contribute to the prevalence of bla NDM– 7 in China. The high prevalence of NDM variants worldwide highlights the critical need for careful monitoring and control of the rapid dissemination of bla NDM .

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“…In K. pneumoniae, the terms "hypervirulence" primarily referred to isolates displaying hypermucoviscosity and causing invasive infections. However, most recent studies viewed the pVir + -KPC-kp strains associated with an extremely high infectious mortality as CR-hvKP, even if there was a lack of clinical features due to hvKP infections [11,13]. In present study, we compared some well-recognized parameters that could assist in differentiating infection due to hypervirulent and classical K. pneumoniae strains (such as infection development location, patients' age and abscess formation) [1], there was no difference between two groups.…”

Section: Discussionmentioning

confidence: 99%

“…It is a common sense that KPC-producing K. pneumoniae (KPC-kp) is absent of pVir and nearly avirulent experimentally [10]. However, convergent K. pneumoniae strains of widely distributed ST11 carrying both pVir and KPC (pVir + -KPC-kp) have emerged, especially in China [11][12][13]. So far, most cases of pVir + -KPC-kp infections were still isolated or sporadic.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology and clinical significance of pLVPK-like virulence plasmid in KPC-2-producing Klebsiella pneumoniae infections in eastern China: a preliminary exploration

Xu¹,

Yang²,

Liu³

et al. 2020

Preprint

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Background: By acquiring a pLVPK-like virulence plasmid (pVir), Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-kp) evolves to a hypervirulent variant, with increasing cases reported worldwide. However, little is known about the epidemiological trend of pVir in KPC-kp, as well as clinical characteristics of infections caused by this novel strain (pVir+-KPC-kp). Methods: From 2014-2018, 662 carbapenem-resistant K. pneumoniae (CRKP) were consecutively collected from a tertiary hospital of eastern China. The confirmed KPC-kp were subjected to antimicrobial susceptibility testing, multilocus sequence typing and detection of pLVPK-related genetic loci (rmpA, rmpA2, iucA and iroN) to identify pVir+-KPC-kp strains. Then, the clinical characteristics and outcomes of KPC-kp infection patients with and without pVir were compared. Moreover, the risk factors for pVir+-KPC-kp infections also determined by a multivariable logistic regression analysis.Results: of the 662 CRKP, 86.6% (573/662) were KPC-kp including 285 (49.7%) pVir+-KPC-kp and 288 (50.3%) pVir--KPC-kp. Notably, the prevalence of pVir+-KPC-kp by year increased remarkably from 2014 (19.5%, 8/41) to 2018 (60.0%, 90/150). Sequence type (ST) 11 was the most predominant ST, accounting for 88.9% of all pVir+-KPC-kp. For the 352 KPC-kp infection cases (186 with pVir+-KPC-kp and 166 with pVir--KPC-kp), multivariable analysis indicated neurosurgery (Odds ratio [OR], 2.92; 95% confidence interval [CI], 1.48-5.75; P =0.002) was independently associated with pVir+-KPC-kp infections. Although patients with pVir+-KPC-kp infections had higher incidence of septic shock (31.2% vs. 21.1%, P =0.03), the two groups showed no significant differences in 7-day mortality (23.1% vs. 18.1%, P =0.24) or 28-day mortality (45.7% vs. 44.0%, P =0.75). Conclusions: Altogether, wide dissemination of pVir in ST11 KPC-kp has emerged in China. Neurosurgery is an independent risk factor for acquisition of pVir+-KPC-kp infections. The mortality rates were similar between patients infected with pVir+-KPC-kp or pVir--KPC-kp, suggesting uncertain impact of pVir in clinical outcome.

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An Outbreak of Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae in an Intensive Care Unit of a Major Teaching Hospital in Wenzhou, China

Cited by 68 publications

References 68 publications

The Small Protein RmpD Drives Hypermucoviscosity in Klebsiella pneumoniae

The Small Protein RmpD Drives Hypermucoviscosity in Klebsiella pneumoniae

Genotypic and Phenotypic Characterization of blaNDM–7-Harboring IncX3 Plasmid in a ST11 Klebsiella pneumoniae Isolated From a Pediatric Patient in China

Epidemiology and clinical significance of pLVPK-like virulence plasmid in KPC-2-producing Klebsiella pneumoniae infections in eastern China: a preliminary exploration

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