Potential role of avibactam in restoring susceptibility in Escherichia coli with two copies of bla and PBP3 mutations.

UNLABELLED

The emergence of carbapenemase-producing represents a significant clinical challenge. Resistance mechanisms involve carbapenemase production, porin and efflux pump alterations, penicillin-binding protein (PBP) modifications, and biofilm formation. This study characterizes a KPC- and a concurrent isolate harboring the same resistance genes, with also exhibiting PBP3 mutations. Whole-genome sequencing and plasmid analysis identified an IncFII(K) plasmid carrying the gene. Both strains shared two resistance genes (, ). contained a single copy of on Tn, whereas carried two copies on separate Tn transposons. Plasmid reconstruction revealed high homology (99.85%) with plasmid pECAZ147_KPC and plasmid pKPC. This suggests that transposon-mediated transfer between the two strains may have occurred via the same plasmid. Moreover, harbored PBP3 mutations (A233T, I332V), which have been previously linked to increased ceftazidime MICs and two missense mutations in . Despite carrying two copies of the gene, along with and PBP3 mutations, our isolate did not exhibit a significant increase in ceftazidime/avibactam MIC. This phenomenon could be explained by avibactam’s ability to bind to PBP2, potentially compensating for the reduced binding of ceftazidime to the mutated PBP3.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1038/s41598-025-07624-z.