Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime–Avibactam in an ST11 Klebsiella pneumoniae Strain DOI Creative Commons

Yanqiao Gong,

Yu Feng, Xiaoju Lv

et al.

Microorganisms, Journal Year: 2024, Volume and Issue: 12(6), P. 1193 - 1193

Published: June 13, 2024

This study describes KPC-204, a novel variant of Klebsiella pneumoniae carbapenemase, characterized by Lys-Asp-Asp (KDD) amino acid insertion at Ambler position 269 deviates from KPC-2. was identified in an ST11-type clinical isolate carbapenem-resistant China. Notably, KPC-204 exhibits resistance to both ceftazidime-avibactam and carbapenems. Genetic analysis revealed that blaKPC-204 located on highly mobile IncFII/IncR plasmid within complex genetic structure facilitates its spread. Functional analysis, achieved through cloning into E. coli DH5α, validates KPC-204’s contribution increased ceftazidime-avibactam. The kinetic parameters showed exhibited similar affinity KPC-2 toward ceftazidime reduced sensitivity avibactam. Docking simulations weaker interaction between avibactam compared Mating experiments demonstrated the resistance’s transmissibility. investigation underscores evolving diversity KPC variants affecting resistance, highlighting necessity for continuous monitoring.

Language: Английский

Hypervirulent and carbapenem-resistant Klebsiella pneumoniae: A global public health threat DOI

Ting-yu Lei,

Bin-bin Liao,

Liang-Rui Yang

et al.

Microbiological Research, Journal Year: 2024, Volume and Issue: 288, P. 127839 - 127839

Published: Aug. 11, 2024

Language: Английский

Citations

11
Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol DOI Creative Commons
Gabriele Bianco, Matteo Boattini, Monica Cricca

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(12), P. 14132 - 14153

Published: Dec. 14, 2024

In recent years, novel antimicrobials have been developed to counter the emergence of antimicrobial resistance and provide effective therapeutic options against multidrug-resistant (MDR) Gram-negative bacilli (GNB). Cefiderocol, a siderophore cephalosporin, represents valuable drug for treatment infections caused by MDR-GNB. The mechanism cefiderocol penetrate through outer membrane bacterial cells, termed “Trojan horse”, makes this unique immune various strategies adopted GNB. Its broad spectrum action, potent antibacterial activity, pharmacokinetics properties, safety, tolerability make key due MDR strains. Although molecule contributed revolutionizing armamentarium MDR-GNB, cefiderocol-resistant strains has redefined its role in clinical practice required new preserve activity. review, we an updated discussion regarding emerging mechanisms resistance, pharmacokinetic/pharmacodynamic (PK/PD) efficacy data major bacteria future prospects.

Language: Английский

Citations

4
Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae DOI Creative Commons
Riccardo Polani,

Alice De Francesco,

Dario Tomolillo

et al.

Emerging infectious diseases, Journal Year: 2024, Volume and Issue: 31(1)

Published: Dec. 18, 2024

Cefiderocol (FDC), a siderophore-cephalosporin conjugate, is the newest option for treating infection with carbapenem-resistant gram-negative bacteria. We identified novel mechanism contributing to decreased FDC susceptibility in Klebsiella pneumoniae clinical isolates. The involves 2 coresident plasmids: pKpQIL, carrying variants of bla

Language: Английский

Citations

4
Circulation of a Unique Klebsiella pneumoniae Clone, ST147 NDM-1/OXA-48, in Two Diverse Hospitals in Calabria (Italy) DOI Creative Commons
Emanuele Nicitra,

Morena Terrana,

Dafne Bongiorno

et al.

Antibiotics, Journal Year: 2025, Volume and Issue: 14(2), P. 128 - 128

Published: Jan. 26, 2025

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae has become endemic in Europe, including Italy, where its prevalence risen dramatically, primarily due to epidemic clones harboring metallo-enzymes. This study aims investigate the dissemination of K. strains co-producing OXA-48 and NDM-1 between two hospitals southern Italy using molecular analyses. Methods: A total 49 strains, predominantly NDM-1, were collected March December 2023. Antibiotic susceptibility testing was conducted following EUCAST guidelines. Whole-genome sequencing (Illumina MiSeq) bioinformatics tools (CARD, CLC Genomics Workbench) used identify resistance virulence genes, capsule loci, phylogenetic relationships. Results: All isolates exhibited multidrug-resistant or extensively drug-resistant profiles, ceftazidime/avibactam meropenem/vaborbactam. Genomic analysis revealed diverse genes such as blaOXA-48, blaNDM-1, blaCTX-M-15, blaSHV variants. Virulence associated with capsules, fimbriae, siderophores widespread. Most classified ST147 by MLST contained various plasmids known carry antimicrobial resistance. Phylogenetic confirmed their clonal relatedness, highlighting intra-hospital high-risk clones. Conclusions: High-risk clones, particularly ST147, pose significant challenges healthcare settings extensive driven plasmid-borne those that co-produce carbapenemases, like blaNDM-1 blaOXA-48. Molecular monitoring these is essential for improving targeted infection control strategies, mitigating spread pathogens, managing clinical impact effectively.

Language: Английский

Citations

0
Investigation on Klebsiella pneumoniae in the field of extracellular vesicles DOI Creative Commons
Jun Wu, Yuheng Liu, Jin Su

et al.

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract Klebsiella pneumoniae (KP), recognized for its pronounced antibiotic resistance, is a prevalent agent of nosocomial infections such as hospital‐acquired pneumonia. The alarming rate serious and associated mortality renders KP significant public health threat. Extracellular vesicles (EVs) are pivotal in KP's physiological pathological mechanisms, facilitating material information transfer mediating interactions between the bacteria host. critical role EVs enhances our understanding pathophysiology, disease progression, strategies infection control. This review emphasizes mechanics resistance instrumental bacterium‐host interplay, proposing promising research focus advancing diagnosis, therapy, prevention.

Language: Английский

Citations

0
Global molecular epidemiology of the incomplete CirA protein related to cefiderocol resistance in Klebsiella pneumoniae : a genome-based study DOI Creative Commons
Haiyan Long,

Yu Feng,

Zhiyong Zong

et al.

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

ABSTRACT CirA is an iron transporter comprising 657 amino acids in Klebsiella pneumoniae, and incomplete alone leads to reduced susceptibility cefiderocol. We performed a genome-based analysis study the prevalence of K. pneumoniae through analyzing all genomes this species ( n = 55,517, as 26 October 2023) available NCBI. detected 633 (1.27%) with corresponding strains collected since 1911, across 44 countries on six continents, mostly 563, 88.94%) from humans. Notably, 77 (12.16%) had combination β-lactamases (NDM-1, NDM-5, NDM-7, or KPC-3 plus SHV-11) known confer cefiderocol resistance. identified 189 variants CirA, including two particularly common ones, 362-amino-acid remnant due frameshift by deletion at cirA nucleotide position 1,083 (116/633, 18.33%) 562-amino-acid premature stop resulting mutation 1,684 (71/633, 11.22%). The was mainly found ST26 (39/116), ST34 (36/116), ST359 (31/116) strains. almost exclusive ST86 (69/71), related hypervirulent capsule type K2. Clonal outbreaks (ST26 USA, UK, Vietnam) cross-border transmission (ST34 UK Portugal) were observed. However, has limitations, analyzed publicly assemblies are biased, only mutations considered. In conclusion, global concern, highlighting urgent need for heightened vigilance further studies. IMPORTANCE Cefiderocol critically important antimicrobial agent against multidrug-resistant organisms carbapenem-resistant . genome-mining (an transporter), which resistance, small proportion genomes. globally distributed have been present over century, well before clinical use One hundred eighty-nine identified, suggesting multifactorial causes. Almost ST26, ST34, wide geographic distribution, pointing potential existence particular lineages prone develop resistance detected. Incomplete associated K2-ST86 lineage high-risk multidrug ST16 clone, posing increased threat challenge treatment infection control.

Language: Английский

Citations

0
The contribution of porins to enterobacterial drug resistance DOI
Anne Davin‐Regli, Jean‐Marie Pagès, Julia Vergalli

et al.

Journal of Antimicrobial Chemotherapy, Journal Year: 2024, Volume and Issue: 79(10), P. 2460 - 2470

Published: Aug. 29, 2024

In Enterobacteriaceae, susceptibility to cephalosporins and carbapenems is often associated with membrane enzymatic barrier resistance. For about 20 years, a large number of Klebsiella pneumoniae, Escherichia coli Enterobacter cloacae presenting ß-lactam resistance have been isolated from medical clinics. addition, some the resistant isolates exhibited alterations in outer porin OmpC-OmpF orthologues, resulting complete absence gene expression, replacement by another or mutations affecting channel properties. Interestingly, for reported major changes pore function were found be present encoding OmpC. The located constriction region amino acid substitutions induce severe restriction lumen diameter and/or alteration electrostatic field that governs diffusion charged molecules. This functional adaptation through porins maintains entry solutes necessary bacterial growth but critically controls influx harmful molecules such as β-lactams at reduced cost. data recently published show importance understanding underlying parameters uptake antibiotics infectious bacteria. Furthermore, development reliable methods measure concentration within cells key combat impermeability-resistance mechanisms.

Language: Английский

Citations

3
Spread and evolution of blaKPC-plasmid between Serratia marcescens and Klebsiella pneumoniae DOI
Weiwei Yang, Chengkang Tang, Siquan Shen

et al.

International Journal of Antimicrobial Agents, Journal Year: 2024, Volume and Issue: 63(5), P. 107149 - 107149

Published: March 19, 2024

Language: Английский

Citations

2
Overexpression of β-lactamase genes ( bla KPC, bla SHV ) and novel CirA deficiencies contribute to decreased cefiderocol susceptibility in carbapenem-resistant Klebsiella pneumoniae before its approval in China DOI
Hanxu Hong,

Lin-Ping Fan,

Wenbo Shi

et al.

Antimicrobial Agents and Chemotherapy, Journal Year: 2024, Volume and Issue: 68(11)

Published: Oct. 10, 2024

ABSTRACT Cefiderocol (FDC) is an effective antibiotic that used to treat severe infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). The mechanisms underlying FDC resistance and molecular epidemiology in China remain unclear. We collected 477 non-duplicate CRKP clinical isolates central characterized their susceptibility FDC, virulence genes, sequence typing. overall rate of was 99.2% China, which higher than North America Europe (96.1%), with MIC 50/90 values 1/2 mg/L. decrease concentrated the ST11 CRKP-carrying plasmids. Whole-genome sequencing (WGS) quantitative reverse transcription PCR (qRT-PCR) experiments showed serine β-lactamases, especially highly expressed KPC SHV, substantially decreased four non-susceptible (two resistant two intermediate isolates). Notably, different CirA deficiencies, p.E450GfsTer16 p.E133Ter, were found both isolates. In contrast, global WGS data indicate primarily associated NDM variants, predominantly ST307 ST147. Overall, exhibits excellent activity against related high SHV expression, along deficiencies CirA, frequently observed ST11. This remarkably from situation will directly impact choice interventions. Additionally, surveillance imperative.

Language: Английский

Citations

2
Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime-Avibactam in an ST11 Klebsiella Pneumoniae Strain DOI Open Access

Yanqiao Gong,

Yu Feng, Xiaoju Lv

et al.

Published: May 17, 2024

This study describes KPC-204, a novel variant of Klebsiella Pneumoniae carbapenemase, characterized by KDD amino acid insertion at Ambler position 269 deviates from KPC-2. was identified in an ST11-type clinical isolate carbapenem-resistant China. Notably, KPC-204 exhibits resistance to both ceftazidime-avibactam and carbapenems. Genetic analysis revealed that blaKPC-204 located on highly mobile IncFII/IncR plasmid within complex genetic structure facilitates its spread. Functional analysis, achieved through cloning into E. coli DH5α, validates KPC-204's contribution increased ceftazidime-avibactam. The kinetic parameters showed exhibited similar affinity KPC-2 toward ceftazidime reduced sensitivity avibactam. Mating experiments demonstrated the resistance's transmissibility. investigation underscores evolving diversity KPC variants affecting resistance, highlighting necessity for continuous monitoring.

Language: Английский

Citations

1