Emergence of NDM-1–producing <i>Pseudomonas aeruginosa</i> Sequence Type 773 Clone: Shift of Carbapenemase Molecular Epidemiology and Spread of 16S rRNA Methylase Genes in Korea

Choi, Yu Jeong; Kim, Young Ah; Kim, Junglim; Jeong, Seok Hoon; Shin, Jong Hee; Shin, Kyeong Seob; Shin, Jeong Hwan; Kim, Young Ree; Kim, Hyo Soo; Uh, Young; Ryoo, Nam Hee

doi:10.3343/alm.2023.43.2.196

Cited by 12 publications

(9 citation statements)

References 11 publications

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“…Previous reports from Pakistan detected bla NDM-1 , bla IMP , bla VIM , bla OXA-48 carbapenemases in CRPA [21,71,72,85,93,94]. These findings are supported by various global reports [14,73,90,[95][96][97][98][99][100][101]. On the other hand, the detection of bla KPC among CRPA was reported infrequently in Pakistan [94]; however, an increasing trend in the global dissemination of bla KPC -harboring P. aeruginosa has been observed [22,28,[102][103][104][105][106][107][108].…”

Section: Discussionsupporting

confidence: 54%

Molecular Analysis of Carbapenem and Aminoglycoside Resistance Genes in Carbapenem-Resistant Pseudomonas aeruginosa Clinical Strains: A Challenge for Tertiary Care Hospitals

Gondal,

Choudhry,

Niaz

et al. 2024

Antibiotics

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Carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) strains have become a global threat due to their remarkable capability to survive and disseminate successfully by the acquisition of resistance genes. As a result, the treatment strategies have been severely compromised. Due to the insufficient available data regarding P. aeruginosa resistance from Pakistan, we aimed to investigate the resistance mechanisms of 249 P. aeruginosa strains by antimicrobial susceptibility testing, polymerase chain reaction for the detection of carbapenemases, aminoglycoside resistance genes, extended-spectrum beta-lactamases (ESBLs), sequence typing and plasmid typing. Furthermore, we tested silver nanoparticles (AgNPs) to evaluate their in vitro sensitivity against antimicrobial-resistant P. aeruginosa strains. We observed higher resistance against antimicrobials in the general surgery ward, general medicine ward and wound samples. Phenotypic carbapenemase-producer strains comprised 80.7% (201/249) with 89.0% (179/201) demonstrating genes encoding carbapenemases: blaNDM-1 (32.96%), blaOXA48 (37.43%), blaIMP (7.26%), blaVIM (5.03%), blaKPC-2 (1.12%), blaNDM-1/blaOXA48 (13.97%), blaOXA-48/blaVIM (1.68%) and blaVIM/blaIMP (0.56%). Aminoglycoside-modifying enzyme genes and 16S rRNA methylase variants were detected in 43.8% (109/249) strains: aac(6′)-lb (12.8%), aac(3)-lla (12.0%), rmtB (21.1%), rmtC (11.0%), armA (12.8%), rmtD (4.6%), rmtF (6.4%), rmtB/aac(3)-lla (8.2%), rmtB/aac(6′)-lla (7.3%) and rmtB/armA (3.6%). In total, 43.0% (77/179) of the strains coharbored carbapenemases and aminoglycoside resistance genes with 83.1% resistant to at least 1 agent in 3 or more classes and 16.9% resistant to every class of antimicrobials tested. Thirteen sequence types (STs) were identified: ST235, ST277, ST234, ST170, ST381, ST175, ST1455, ST1963, ST313, ST207, ST664, ST357 and ST348. Plasmid replicon types IncFI, IncFII, IncA/C, IncL/M, IncN, IncX, IncR and IncFIIK and MOB types F11, F12, H121, P131 and P3 were detected. Meropenem/AgNPs and Amikacin/AgNPs showed enhanced antibacterial activity. We reported the coexistence of carbapenemases and aminoglycoside resistance genes among carbapenem-resistant P. aeruginosa with diverse clonal lineages from Pakistan. Furthermore, we highlighted AgNP’s potential role in handling future antimicrobial resistance concerns.

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Section: Discussionsupporting

confidence: 54%

Molecular Analysis of Carbapenem and Aminoglycoside Resistance Genes in Carbapenem-Resistant Pseudomonas aeruginosa Clinical Strains: A Challenge for Tertiary Care Hospitals

Gondal,

Choudhry,

Niaz

et al. 2024

Antibiotics

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“…A recent study conducted in Korea revealed that bla NDM-1 was among the most detected metallo-beta-lactamase genes in carbapenem-resistant P. aeruginosa isolates. This highlights the significance of bla NDM-1 in contributing to carbapenem resistance in P. aeruginosa strains [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Resistance, Genetic Lineages, and Biofilm Formation in Pseudomonas aeruginosa Isolated from Human Infections: An Emerging One Health Concern

Silva,

López

et al. 2023

Antibiotics

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Pseudomonas aeruginosa (PA) is a leading nosocomial pathogen and has great versatility due to a complex interplay between antimicrobial resistance and virulence factors. PA has also turned into one the most relevant model organisms for the study of biofilm-associated infections. The objective of the study focused on analyzing the antimicrobial susceptibility, resistance genes, virulence factors, and biofilm formation ability of thirty-two isolates of PA. PA isolates were characterized by the following analyses: susceptibility to 12 antimicrobial agents, the presence of resistance genes and virulence factors in PCR assays, and the quantification of biofilm production as evaluated by two distinct assays. Selected PA isolates were analyzed through multilocus sequence typing (MLST). Thirty PA isolates have a multi-resistant phenotype, and most of the isolates showed high levels of resistance to the tested antibiotics. Carbapenems showed the highest prevalence of resistance. Various virulence factors were detected and, for the quantification of biofilm production, the effectiveness of different methods was assessed. The microtiter plate method showed the highest accuracy and reproducibility for detecting biofilm-producing bacteria. MLST revealed four distinct sequence types (STs) in clinical PA, with three of them considered high-risk clones of PA, namely ST175, ST235, and ST244. These clones are associated with multidrug resistance and are prevalent in hospitals worldwide. Overall, the study highlights the high prevalence of antibiotic resistance, the presence of carbapenemase genes, the diversity of virulence factors, and the importance of biofilm formation in PA clinical isolates. Understanding these factors is crucial for effective infection control measures and the development of targeted treatment strategies.

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“…The growing prevalence and global spread of the multidrug resistance profiles of MBL-producing P. aeruginosa [ 54 ] warn of the occurrence of epidemic outbreaks. Recent antimicrobial resistance surveys in South Korea have revealed an increase in the carbapenem resistance rate of P. aeruginosa isolates [ 55 ]. Given the clinical importance of MBL-producing P. aeruginosa , we used 21 clinical isolates of P. aeruginosa expressing either NDM or IMP collected from patients admitted to a university hospital in Seoul, Korea ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Potentiation of Antibiotic Activity of Aztreonam against Metallo-β-Lactamase-Producing Multidrug-Resistant Pseudomonas aeruginosa by 3-O-Substituted Difluoroquercetin Derivatives

Lee,

Kim

et al. 2024

Pharmaceutics

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The combination of aztreonam (ATM) and ceftazidime–avibactam (CAZ-AVI; CZA) has shown therapeutic potential against serine-β-lactamase (SBL)- and metallo-β-lactamase (MBL)-producing Enterobacterales. However, the ability of CZA to restore the antibiotic activity of ATM is severely limited in MBL-producing multidrug-resistant (MDR) Pseudomonas aeruginosa strains because of the myriad of intrinsic and acquired resistance mechanisms associated with this pathogen. We reasoned that the simultaneous inhibition of multiple targets associated with multidrug resistance mechanisms may potentiate the antibiotic activity of ATM against MBL-producing P. aeruginosa. During a search for the multitarget inhibitors through a molecular docking study, we discovered that di-F-Q, the previously reported efflux pump inhibitor of MDR P. aeruginosa, binds to the active sites of the efflux pump (MexB), as well as various β-lactamases, and these sites are open to the 3-O-position of di-F-Q. The 3-O-substituted di-F-Q derivatives were thus synthesized and showed hereto unknown multitarget MDR inhibitory activity against various ATM-hydrolyzing β-lactamases (AmpC, KPC, and New Delhi metallo-β-lactamase (NDM)) and the efflux pump of P. aeruginosa, presumably by forming additional hydrophobic contacts with the targets. The multitarget MDR inhibitor 27 effectively potentiated the antimicrobial activity of ATM and reduced the MIC of ATM more than four-fold in 19 out of 21 MBL-producing P. aeruginosa clinical strains, including the NDM-producing strains which were highly resistant to various combinations of ATM with β-lactamase inhibitors and/or efflux pump inhibitors. Our findings suggest that the simultaneous inhibition of multiple MDR targets might provide new avenues for the discovery of safe and efficient MDR reversal agents which can be used in combination with ATM against MBL-producing MDR P. aeruginosa.

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Emergence of NDM-1–producing Pseudomonas aeruginosa Sequence Type 773 Clone: Shift of Carbapenemase Molecular Epidemiology and Spread of 16S rRNA Methylase Genes in Korea

Cited by 12 publications

References 11 publications

Molecular Analysis of Carbapenem and Aminoglycoside Resistance Genes in Carbapenem-Resistant Pseudomonas aeruginosa Clinical Strains: A Challenge for Tertiary Care Hospitals

Molecular Analysis of Carbapenem and Aminoglycoside Resistance Genes in Carbapenem-Resistant Pseudomonas aeruginosa Clinical Strains: A Challenge for Tertiary Care Hospitals

Antimicrobial Resistance, Genetic Lineages, and Biofilm Formation in Pseudomonas aeruginosa Isolated from Human Infections: An Emerging One Health Concern

Potentiation of Antibiotic Activity of Aztreonam against Metallo-β-Lactamase-Producing Multidrug-Resistant Pseudomonas aeruginosa by 3-O-Substituted Difluoroquercetin Derivatives

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