Global silent transmission of the class A ß-lactamase LAP-2 by plasmid transfer and clonal expansion of Klebsiella pneumoniae lineagesFIRST REVIEW ROUND - REVIEWERS COMMENTSAUTHORS RESPONSE TO REVIEWERSREVIEWERS COMMENTS.

BACKGROUND Narrow-spectrum antibiotics, such as narrow-spectrum β-lactams, have been pointed out as an efficient strategy to mitigate resistance and reach successful outcomes in treating enterobacterial infections. The narrow-spectrum class A β-lactamase LAP-2, conferring resistance to narrow-spectrum cephalosporins/penicillin derivatives, is spread among Enterobacteriaceae from Asia but is rarely reported in the Americas. Due to the lack of information concerning the bla LAP-2 genetic background involved with its dissemination, this study determined the bla LAP-2 genomic environment and contextualised the LAP-2-positive Klebsiella pneumoniae strains from Brazil in the current epidemiological scenario.

OBJECTIVES This study characterised LAP-2-positive K. pneumoniae strains, focusing on their genetic environment and epidemiology.

METHODS Whole-genome sequencing and in silico analyses were performed to identify the genetic context of bla LAP-2 in five clinical isolates from Brazil. Comparative genomics and phylogenomic analysis were conducted to investigate the transmission dynamics of bla LAP-2 globally.

FINDINGS The bla LAP-2 gene was embedded in a conserved genetic module (IS3-bla LAP-2-ftsI), facilitating its dissemination among diverse Enterobacteriaceae species. The Brazilian strains harboured bla LAP-2 within a pXJ-K2 variant plasmid, a key vector in LAP-2 spread. Phylogenomic analysis revealed that, in Brazil, bla LAP-2 was carried by an ST11 K. pneumoniae lineage distinct from the Chinese lineage but globally disseminated.

MAIN CONCLUSIONS This study provides insights into the epidemiology and transmission dynamics of bla LAP-2, revealing its silent spread via plasmid transfer and clonal expansion of ST11 lineages. The high transmission potential of bla LAP-2 may compromise the application of narrow-spectrum β-lactams as a viable treatment option for enterobacteria-causing infections.