Dissemination of Metallo-β-Lactamase-Producing Pseudomonas aeruginosa in Serbian Hospital Settings: Expansion of ST235 and ST654 Clones

Abstract

This nationwide study aimed to investigate the molecular characteristics of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa in Serbia, underlying resistance mechanisms, the genetic context of detected MBL genes, and the clonal relationship between isolates harboring genes-encoding MBL. Overall, 320/5334 isolates collected from 2018 to 2021 were identified as P. aeruginosa. Carbapenem-resistant P. aeruginosa (CRPA) were screened for the presence of blaVIM, blaIMP, and blaNDM, genes whereas MBL-positive isolates were tested for the presence of the blaCTX-M-2, blaPER, blaTEM, blaSHV, blaVEB, and blaGES. Multilocus sequence typing and phylogenomic analysis were performed for P. aeruginosa-producing MBL. The majority of the P. aeruginosa isolates were recovered from the lower respiratory tract (n = 120; 37.5%) and wound specimens (n = 108; 33.75%). CRPA isolates accounted for 43.1% (n = 138) of the tested isolates, 31 out of them being blaNDM-1-positive (22.5%). The colistin resistance rate was 0.3%. MLST analysis revealed the occurrence of ST235 (n = 25) and ST654 (n = 6), mostly confined to Serbia. The distribution of beta-lactamase-encoding genes in these isolates suggested clonal dissemination and possible recombination: ST235/blaNDM-1, ST235/blaNDM-1/blaPER-1, ST654/blaNDM-1, ST654/blaNDM-1/blaPER-1, and ST654/blaNDM-1/blaGES-5. High-risk clones ST235 and ST654 identified for the first time in Serbia, are important vectors of acquired MBL and ESBL and their associated multidrug resistance phenotypes represent a cause for considerable concern.

Antibiotic influx and efflux in Pseudomonas aeruginosa: Regulation and therapeutic implications

“…Since antibiotic resistance genes can be carried by mobile genetic elements such as plasmids, transposons, and phages, it is easy for bacteria to acquire antibiotic‐resistant genes through horizontal gene transfer. For example, the acquisition of genes encoding β‐lactamases, which confer resistance to β‐lactam antibiotics, has been frequently reported in P. aeruginosa (Kabic et al., 2023 ). Acquired resistance is also achieved through mutational changes in resistance genes.…”

Whole-Genome Sequencing-Based Resistome Analysis of Nosocomial Multidrug-Resistant Non-Fermenting Gram-Negative Pathogens from the Balkans

“…A recent study investigated the molecular characteristics of MBL-producing CRPA isolates in Serbia, as well as the underlying resistance mechanisms and the genetic context of the MBL genes detected [ 131 ]. Their distribution suggested clonal dissemination and possible recombination.…”

“…Kabic et al also performed detailed phylogenomic analysis by calling and comparing single nucleotide polymorphisms (SNPs) from the core gene alignment of 165 P. aeruginosa genomes, of which four were sequenced by the authors. It should be mentioned that this is the second study form the Balkans that utilizes ONT long reads (MinION) in combination with the short reads generated by an Illumina platform (Illumina HiSeq, 2 × 150 bp) [ 131 ]. This results in the generation of the second complete genome of a CRPA isolate again carrying the bla NDM-1 gene similar to the report from Bulgaria [ 127 ].…”

First Detection and Molecular Characterization of Pseudomonas aeruginosa blaNDM-1 ST308 in Greece

“…NDM-1 has been identified mostly in Escherichia coli , Klebsiella pneumoniae , and, to a lesser extent, Acinetobacter and Pseudomonas . P. aeruginosa strain carriers of the bla NDM-1 -encoding gene have been found to circulate in various countries internationally, belonging in different Sequence Types (STs): ST773 in Libya; STs 38, 773, 235, 357, and 654 in Asia; STs 235 and 654 in Serbia; ST 773 in Korea; ST654 in Chile; ST274 in Ethiopia; ST1966 in China; and ST 308 in Singapore and Malaysia [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”