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Introduction: Burkholderia cepacia complex (Bcc) clonal complex (CC) 31, the predominant lineage causing devastating outbreaks globally, has been a growing concern of infections in non-cystic fibrosis (NCF) patients in India. B. cenocepacia is very challenging to treat owing to its virulence determinants and antibiotic resistance. Improving the management of these infections requires a better knowledge of their resistance patterns and mechanisms., Methods: Whole-genome sequences of 35 CC31 isolates obtained from patient samples, were analyzed against available 210 CC31 genomes in the NCBI database to glean details of resistance, virulence, mobile elements, and phylogenetic markers to study genomic diversity and evolution of CC31 lineage in India., Results: Genomic analysis revealed that 35 isolates belonging to CC31 were categorized into 11 sequence types (ST), of which five STs were reported exclusively from India. Phylogenetic analysis classified 245 CC31 isolates into eight distinct clades (I-VIII) and unveiled that NCF isolates are evolving independently from the global cystic fibrosis (CF) isolates forming a distinct clade. The detection rate of seven classes of antibiotic-related genes in 35 isolates was 35 (100%) for tetracyclines, aminoglycosides, and fluoroquinolones; 26 (74.2%) for sulphonamides and phenicols; 7 (20%) for beta-lactamases; and 1 (2.8%) for trimethoprim resistance genes. Additionally, 3 (8.5%) NCF isolates were resistant to disinfecting agents and antiseptics. Antimicrobial susceptibility testing revealed that majority of NCF isolates were resistant to chloramphenicol (77%) and levofloxacin (34%). NCF isolates have a comparable number of virulence genes to CF isolates. A well-studied pathogenicity island of B . cenocepacia , GI11 is present in ST628 and ST709 isolates from the Indian Bcc population. In contrast, genomic island GI15 (highly similar to the island found in B . pseudomallei strain EY1) is exclusively reported in ST839 and ST824 isolates from two different locations in India. Horizontal acquisition of lytic phage ST79 of pathogenic B . pseudomallei is demonstrated in ST628 isolates Bcc1463, Bcc29163, and BccR4654 amongst CC31 lineage., Discussion: The study reveals a high diversity of CC31 lineages among B. cenocepacia isolates from India. The extensive information from this study will facilitate the development of rapid diagnostic and novel therapeutic approaches to manage B . cenocepacia infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Saroha, Patil, Rana, Kumar, Kumar, Singhal, Gautam and Patil.)

Aim: This study aimed at investigating the association of gene expression of multidrug efflux pumps ( Mex A, Mex C, Mex E, and Mex X), the outer membrane porin Opr D, and the β-lactamase Amp C with the antimicrobial susceptibility among 44 clinical isolates of Burkholderia cepacia complex (Bcc). Results: Increased expression of ampC gene showed significant association with reduced susceptibility to chloramphenicol. In fact, reduced susceptibility to chloramphenicol was correlated with overexpression of most genes ( ampC , mexC , mexE , and mexX ) studied here in majority (>95%) of the Bcc isolates. Increased mexA expression showed significant association with reduced susceptibility to β-lactam antimicrobials (ceftazidime, piperacillin-tazobactam, and meropenem) and co-trimoxazole. Reduced susceptibility to meropenem also showed significant correlation with overexpression of mexC and mexX , whereas reduced susceptibility to ceftazidime was also associated with mexE overexpression. Reduced susceptibility to levofloxacin was significantly associated with overexpression of mexX . The involvement of the efflux pumps in levofloxacin and ceftazidime resistance was further inferred from the finding that the efflux pump inhibitor, carbonyl cyanide m-chlorophenylhydrazone reduced minimum inhibitory concentrations for both the antimicrobials. Conclusions: To conclude, this study explored the high-level expression of mexC , mexE , and mexX efflux pumps genes and ampC in the clinical isolates of Bcc, which can be targeted at treating infections caused by Bcc.

Burkholderia cepacia complex (Bcc) is a complex group of bacteria causing opportunistic infections in immunocompromised and cystic fibrosis (CF) patients. Herein, we report multilocus sequence typing and analysis of the 57 clinical isolates of Bcc collected over the period of seven years (2005-2012) from several hospitals across India. A total of 21 sequence types (ST) including two STs from cystic fibrosis patient's isolates and twelve novel STs were identified in the population reflecting the extent of genetic diversity. Multilocus sequence analysis revealed two lineages in population, a major lineage belonging to B. cenocepacia and a minor lineage belonging to B. cepacia. Split-decomposition analysis suggests absence of interspecies recombination and intraspecies recombination contributed in generating genotypic diversity amongst isolates. Further linkage disequilibrium analysis indicates that recombination takes place at a low frequency, which is not sufficient to break down the clonal relationship. This knowledge of the genetic structure of Bcc population from a rapidly developing country will be invaluable in the epidemiology, surveillance and understanding global diversity of this group of a pathogen.