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Recently, in India, there has been a shift from NDM to OXA48-like carbapenemases. OXA-181 and OXA-232 are the frequently produced variants of OXA48-like carbapenemases. OXA48-like carbapenemases are also known to be carried on transposons such as Tn1999, Tn1999.2 and it is also associated with IS1R carried on Tn1999. In India, there are no previous reports studying the association of mobile genetic elements (MGEs) with OXA48-like carbapenemases. The present study was aimed at determining the genetic backbone of OXA48-like carbapenemases to determine the role of MGEs in its transfer and to investigate the Inc plasmid type carrying bla . A total of 49 carbapenem resistant K. pneumoniae which included 25 isolates from South India and 24 isolates from North India, were included in the study. Whole genome sequencing using Ion Torrent PGM was performed to study the isolates. OXA-232 was present in 35 isolates (71%). In 19 isolates (39%), bla was associated with MGEs. Insertion sequences such as ISX4, IS1, IS3, ISKpn1, ISKpn26, ISKpn25, ISSpu2, ISKox1, IS4321R, ISEc36, and ISPa38; and transposons such as TnAs3 and Tn2, were present. Isolates from northern and southern India belonging to same sequence type (ST) had diverse genetic backbone for bla . ST14 isolates from north had IS5 and Tn3 families while from south they had IS1, IS5 and IS630 families. ST231 from north had IS5, IS6 and Tn3 families with bla while from south, IS1, IS3 and IS5 families were observed; with ISKpn26 being present among isolates from both the regions. bla was predominantly found on ColKP3 plasmid. ST231 was the predominant ST in 22 isolates (45%). OXA-232 is the predominant variant of OXA48-like carbapenemase with ST231 being the commonest ST of OXA48-like carbapenemase producing K. pneumoniae in India. Diverse MGEs have been associated with both bla and bla which contribute to their spread. The MGEs in the present study are different from those reported earlier. There is no clonal expansion of bla producing K. pneumoniae since diverse STs were observed. Monitoring the genetic backbone of OXA48-like carbapenemase is essential to better understand the transmission dynamics of XDR K. pneumoniae.

Globally, the infection rate of carbapenem-resistant (CRKP) producing OXA-48-like carbapenemase is increasing, posing a significant public health threat due to its high antibiotic resistance. Between December 2019 and April 2023, ten CRKP strains carrying the OXA-48-like carbapenemase were isolated from inpatients at the First Affiliated Hospital of Kunming Medical University. Wholegenome sequencing (WGS) revealed that all strains carried the OXA-232 gene, a variant of OXA-48-like, located on the non-conjugative ColKP3 plasmid. Sequence typing identified nine strains as ST231 and one as ST11. The ST231 strains carried common virulence genes, including yersiniabactin (ybtA, fyuA, irp2) and aerobactin (iucABCD, iutA), while the ST11 strain carried high-virulence genes (rmpA, rmpA2, peg-344) as well as KPC-2 and OXA-232 carbapenemase genes on separate plasmids, suggesting that CRKP can harbor multiple plasmids with carbapenemase genes. Sequence typing of 264 global ST231 CRKP isolates (n = 264) showed a distinct clonal relationship between our strains and Indian CRKP isolates, indicating potential cross-border transmission. The virulence potential and immune response of the ST231 strains were assessed using a mouse respiratory infection model. The concentrations of inflammatory factors CCL2/MCP-1, IL-6, and TNF-α in the alveolar lavage fluid and blood of the model mice were detected. Combined with the pathological analysis of lung and liver tissues, it reveals variability in virulence and immune response despite carrying identical resistance and virulence genes. This underscores the urgent need for monitoring and tailored public health strategies to combat the global spread of drug-resistant strains.