IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible Klebsiella pneumoniae

Kubota, Hiroaki; Suzuki, Yasunori; Okuno, Rumi; Uchitani, Yumi; Ariyoshi, Tsukasa; Takemura, Nobuyuki; Mihara, Fuminori; Mezaki, Kazuhisa; Ohmagari, Norio; Matsui, Mari; Suzuki, Satowa; Sekizuka, Tsuyoshi; Kuroda, Makoto; Yokoyama, Keiko; Sadamasu, Kenji

doi:10.1128/msphere.00736-19

Cited by 18 publications

(17 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…β-Lactamases are bacterial enzymes that hydrolyze the β-lactam ring of β-lactam antibiotics and have been implicated in the emergence of antibiotic-resistant pathogenic bacteria [53,54]. Novel β-lactamase genes are continuously being found in clinical and environmental bacterial populations [55][56][57], threatening patients with potentially untreatable pathogenic infections. The presence of these two novel β-lactamase genes in freshwater viromes suggests another threat to public health.…”

Section: Discussionmentioning

confidence: 99%

Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes

et al. 2020

View full text Add to dashboard Cite

Background: Antibiotic resistance developed by bacteria is a significant threat to global health. Antibiotic resistance genes (ARGs) spread across different bacterial populations through multiple dissemination routes, including horizontal gene transfer mediated by bacteriophages. ARGs carried by bacteriophages are considered especially threatening due to their prolonged persistence in the environment, fast replication rates, and ability to infect diverse bacterial hosts. Several studies employing qPCR and viral metagenomics have shown that viral fraction and viral sequence reads in clinical and environmental samples carry many ARGs. However, only a few ARGs have been found in viral contigs assembled from metagenome reads, with most of these genes lacking effective antibiotic resistance phenotypes. Owing to the wide application of viral metagenomics, nevertheless, different classes of ARGs are being continuously found in viral metagenomes acquired from diverse environments. As such, the presence and functionality of ARGs encoded by bacteriophages remain up for debate. Results: We evaluated ARGs excavated from viral contigs recovered from urban surface water viral metagenome data. In virome reads and contigs, diverse ARGs, including polymyxin resistance genes, multidrug efflux proteins, and β-lactamases, were identified. In particular, when a lenient threshold of e value of ≤ 1 × e −5 and query coverage of ≥ 60% were employed in the Resfams database, the novel β-lactamases bla HRV-1 and bla HRVM-1 were found. These genes had unique sequences, forming distinct clades of class A and subclass B3 β-lactamases, respectively. Minimum inhibitory concentration analyses for E. coli strains harboring bla HRV-1 and bla HRVM-1 and catalytic kinetics of purified HRV-1 and HRVM-1 showed reduced susceptibility to penicillin, narrow-and extendedspectrum cephalosporins, and carbapenems. These genes were also found in bacterial metagenomes, indicating that they were harbored by actively infecting phages.

show abstract

Section: Discussionmentioning

confidence: 99%

Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes

et al. 2020

View full text Add to dashboard Cite

show abstract

“…These plasmids are now commonly identified among environmental and clinical isolates [29,30]. Because these plasmids are carriers of genes encoding carbapenemases, mostly OXA-48 carbapenemases, they can be regarded as a public health threat [23,28,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44].…”

Section: Discussionmentioning

confidence: 99%

“…The sequence of qacEdelta1-sul1-istB-IS21 was 99.25% identical to that of the plasmid TMTA63632 harboring bla IMP-68 (accession number AP019667) in a K. pneumoniae isolate obtained from a patient in Japan (Figs. 2 and 3) [23]. The plasmid incompatibility complex of pSL264 was IncL/M.…”

Section: Structure Of the Plasmid Harboring Bla Imp-1mentioning

confidence: 99%

A transferrable IncL/M plasmid harboring a gene encoding IMP-1 metallo-β-lactamase in clinical isolates of Enterobacteriaceae

et al. 2021

View full text Add to dashboard Cite

Background The worldwide spread of carbapenemase-producing Enterobacteriaceae (CPE) has reduced the clinical utility of carbapenems. Plasmids often play an important role in the spread of genes encoding drug-resistance factors, especially in the horizontal transfer of these genes among species of Enterobacteriaceae. This study describes a patient infected with three species of CPE carrying an identical transferrable IncL/M plasmid. Methods Clinical isolates of CPE were collected at St. Luke’s International Hospital, Tokyo, Japan, from 2015 to 2019. Three species of CPE isolates, Enterobacter cloacae, Klebsiella aerogenes and Serratia marcescens, were isolated from a patient who developed severe gallstone pancreatitis associated with bloodstream infection, with all three isolates producing IMP-1 metallo-β-lactamase. The complete sequences of the plasmids of the three isolates were determined by both MiSeq and MinION. The medical chart of this patient was retrospectively reviewed conducted to obtain relevant clinical information. Results The three CPE species carried an IncL/M plasmid, pSL264, which was 81,133 bp in size and harbored blaIMP-1. The genetic environment surrounding blaIMP-1 consisted of int1-blaIMP-1-aac(6’)-IIc-qacL-qacEdelta1-sul1-istB-IS21. Conjugation experiments showed that S. marcescens could transmit the plasmid to E. cloacae and K. aerogenes. In contrast, pSL264 could not transfer from E. cloacae or K. aerogenes to S. marcescens. Conclusion The IncL/M plasmid pSL264 harboring blaIMP-1 was able to transfer among different species of Enterobacteriaceae in a patient receiving long-term antimicrobial treatment. The worldwide emergence and spread of IncL/M plasmids harboring carbapenemase-encoding genes among species of Enterobacteriaceae is becoming a serious public health hazard.

show abstract

“…β-Lactamases are bacterial enzymes that hydrolyze the β-lactam ring of β-lactam antibiotics and have been implicated in the emergence of antibiotic-resistant pathogenic bacteria [50,51]. Novel β-lactamase genes are continuously being found in clinical and environmental bacterial populations [52][53][54], threatening patients with potentially untreatable pathogenic infections. The presence of these two novel β-lactamase genes in freshwater and polyvalent, and are difficult to track, making it challenging to predict the dissemination routes of these phage-borne ARGs.…”

Section: Discussionmentioning

confidence: 99%

Freshwater Viral Metagenome Reveals Novel and Functional Phage-borne Antibiotic Resistance Genes

Moon

Kang

Park

et al. 2019

Preprint

View full text Add to dashboard Cite

BackgroundAntibiotic resistance developed by bacteria is a significant threat to global health. Antibiotic resistance genes (ARGs) spread across different bacterial populations through multiple dissemination routes, including horizontal gene transfer mediated by bacteriophages. ARGs carried by bacteriophages are considered especially threatening due to their prolonged persistence in the environment, fast replication rates, and ability to infect phylogenetically remote bacterial hosts. Several studies employing qPCR and viral metagenomics have shown that viral fraction and viral sequence reads in clinical and environmental samples carry many ARGs. However, only a few ARGs have been found in viral contigs assembled from metagenome reads, with most of these genes lacking effective antibiotic resistance phenotypes. Owing to the wide application of viral metagenomics, nevertheless, different classes of ARGs are being continuously found in viral metagenomes acquired from diverse environments. As such, the presence and functionality of ARGs encoded by bacteriophages remain up for debate.ResultsWe evaluated ARGs excavated from viral contigs recovered from urban surface water viral metagenome data. In virome reads and contigs, diverse ARGs, including polymyxin resistance genes, multidrug efflux proteins, and β-lactamases, were identified. In particular, the novel β-lactamases blaHRV-1 and blaHRVM-1 found in this study had unique sequences, forming distinct clades of Class A and subclass B3 β-lactamases, respectively. Minimum inhibitory concentration analyses for E. coli strains harboring blaHRV-1 and blaHRVM-1 and catalytic kinetics of purified HRV-1 and HRVM-1 showed reduced susceptibility to penicillin, narrow- and extended-spectrum cephalosporins, and carbapenems. These genes were also found in bacterial metagenomes, indicating that they were harbored by actively infecting phages.ConclusionOur results showed that viruses in the environment carry as-yet-unreported functional ARGs, albeit in small quantities. We thereby suggest that environmental bacteriophages could be reservoirs of widely variable, unknown ARGs that could be disseminated via virus-host interactions.

show abstract

IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible Klebsiella pneumoniae

Cited by 18 publications

References 24 publications

Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes

Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes

A transferrable IncL/M plasmid harboring a gene encoding IMP-1 metallo-β-lactamase in clinical isolates of Enterobacteriaceae

Freshwater Viral Metagenome Reveals Novel and Functional Phage-borne Antibiotic Resistance Genes

Contact Info

Product

Resources

About