Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 Escherichia coli High-Risk Clone

Hernández-García, Marta; Sánchez-López, Javier; Martínez-García, Laura; Becerra-Aparicio, Federico; Morosini, María Isabel; Ruíz-Garbajosa, Patricia

doi:10.3390/pathogens10010067

Cited by 20 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNA sequencing of the bla KPC genes was obtained for the 32 strains showing resistance or reduced susceptibility to CZA. Nine different KPC-3 protein variants were identified: four previously described, namely, KPC-29 (WP_096807439), KPC-31 (WP_073668892), KPC-39 (WP_128268237), and KPC-49 (WP_197749402) (36), and five never previously reported, assigned by GenBank as KPC-66 to KPC-70 (Fig. 1).…”

Section: Resultsmentioning

confidence: 96%

Evolutionary Trajectories toward Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Clinical Isolates

Carattoli

Arcari

Bibbolino

et al. 2021

Antimicrob Agents Chemother

View full text Add to dashboard Cite

From January 2019 to April 2020, 32 KPC-producing, ceftazidime-avibactam (CZA) resistant Klebsiella pneumoniae strains were isolated in a university hospital in Rome, Italy. These strains belonged to the ST512, ST101 and ST307 high-risk clones. Nine different CZA-resistant KPC-3 protein variants were identified, five of them never previously reported (KPC-66 to KPC-70). Among them, KPC-31, KPC-39, KPC-49, KPC-66, KP-68, KPC-69 and KPC-70 showed amino acid substitutions, insertions and deletions in the Ω loop of the protein. KPC-29 has the duplication, while the novel KPC-67 has the triplication of the KDD triplet in the 270-loop of the protein. Genomics performed on contemporary resistant and susceptible clones underlined that those novel mutations emerged in bla KPC-3 genes located on conserved plasmids: in ST512, all bla KPC-3 mutant genes were located in pKpQIL plasmids, while the three novel bla KPC-3 mutants identified in ST101 were on FIIk-FIA(HI1)-R plasmids. Selection also promoted multiplication of the carbapenemase gene copy number by transposition, recombination, and fusion of resident plasmids. When expressed in Escherichia coli recipient cells cloned in the high-copy number pTOPO vector, the Ω loop mutated variants showed CZA-resistant phenotype associated with susceptibility to carbapenems, while KPC variants with insertions in the 270-loop showed residual activity on carbapenems. The investigation of CZA-resistance mechanisms offered the unique opportunity to study vertical, horizontal, and oblique evolutionary trajectories of K. pneumoniae high-risk clones.

show abstract

Section: Resultsmentioning

confidence: 96%

Evolutionary Trajectories toward Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Clinical Isolates

Carattoli

Arcari

Bibbolino

et al. 2021

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…This variant was formerly identified as the KPC-3 variant. 36 The newly discovered variant in ST859 conferred resistance to both ceftazidime–avibactam and several carbapenems, distinguishing it from the KPC-49 variant in E. coli mentioned above. The KPC-49 variant in E. coli regained susceptibility to imipenem and meropenem.…”

Section: Discussionmentioning

confidence: 97%

Phenotypic and Genetic Analysis of KPC-49, a KPC-2 Variant Conferring Resistance to Ceftazidime–Avibactam and Maintaining Resistance to Imipenem and Meropenem

Meng¹,

Wei²,

Song³

et al. 2023

IDR

View full text Add to dashboard Cite

Klebsiella pneumoniae, a gram-negative bacterium, poses a severe hazard to public health, with many bacterial hosts having developed resistance to most antibiotics in clinical use. The goal of this study was to look into the development of resistance to both ceftazidime-avibactam and carbapenems, including imipenem and meropenem, in a K. pneumonia strain expressing a novel K. pneumoniae carbapenemase-2 (KPC-2) variant, referred to as KPC-49. Methods: After 1 day of incubation of K1 on agar containing ceftazidime-avibactam (MIC = 16/4 mg/L), a second KPC-producing K. pneumoniae strain (K2) was recovered. Antimicrobial susceptibility assays, cloning assays, and whole genome sequencing were performed to analyse and evaluate antibiotic resistance phenotypes and genotypes. Results: K. pneumoniae strain (K1), that produced KPC-2, was susceptible to ceftazidime-avibactam but resistant to carbapenems. The K2 isolate harboured a novel bla KPC-49 variant, which differs from bla KPC-2 by a single nucleotide (C487A), and results in an arginine-serine substitution at amino acid position 163 (R163S). The mutant K2 strain was resistant to both ceftazidime-avibactam and carbapenems. We demonstrated the ability of KPC-49 to hydrolyse carbapenems, which may be attributed to high KPC-49 expression or presence of an efflux pump and/or absence of membrane pore proteins in K2. Furthermore, bla KPC-like was carried on an IncFII (pHN7A8)/IncR-type plasmid within a TnAs1-orf-orf-orf-orf-orf-orf-ISKpn6-bla KPC -ISKpn27 structure. The bla KPC-like gene was flanked by various insertion sequences and transposon elements, including the Tn3 family transposon, such as TnAs1, TnAs3, IS26, and IS481-ISKpn27. Conclusion: New KPC variants are emerging owing to sustained exposure to antimicrobials and modifications in their amino acid sequences. We demonstrated the drug resistance mechanisms of the new mutant strains through experimental whole genome sequencing combined with bioinformatics analysis. Enhanced understanding of laboratory and clinical features of infections due to K. pneumoniae of the new KPC subtype is key to early and accurate anti-infective therapy.

show abstract

“…The ST131 clone is part of the phylogenetic group B2 and corresponds predominantly to serotype O25b:H4. The rapid and successful dissemination of the high-risk ST131 clone has been attributed mainly to the H30 sublineage, defined by the presence of the specific allele of the fimbrial adhesin, fimH30 [ 89 ].…”

Section: Enterobacteralesmentioning

confidence: 99%

ESKAPE and Beyond: The Burden of Coinfections in the COVID-19 Pandemic

et al. 2023

View full text Add to dashboard Cite

The ESKAPE group constitute a threat to public health, since these microorganisms are associated with severe infections in hospitals and have a direct relationship with high mortality rates. The presence of these bacteria in hospitals had a direct impact on the incidence of healthcare-associated coinfections in the SARS-CoV-2 pandemic. In recent years, these pathogens have shown resistance to multiple antibiotic families. The presence of high-risk clones within this group of bacteria contributes to the spread of resistance mechanisms worldwide. In the pandemic, these pathogens were implicated in coinfections in severely ill COVID-19 patients. The aim of this review is to describe the main microorganisms of the ESKAPE group involved in coinfections in COVID-19 patients, addressing mainly antimicrobial resistance mechanisms, epidemiology, and high-risk clones.

show abstract

Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 Escherichia coli High-Risk Clone

Cited by 20 publications

References 38 publications

Evolutionary Trajectories toward Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Clinical Isolates

Evolutionary Trajectories toward Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Clinical Isolates

Phenotypic and Genetic Analysis of KPC-49, a KPC-2 Variant Conferring Resistance to Ceftazidime–Avibactam and Maintaining Resistance to Imipenem and Meropenem

ESKAPE and Beyond: The Burden of Coinfections in the COVID-19 Pandemic

Contact Info

Product

Resources

About