Genomic and transcriptomic analysis of trimethoprim-sulfamethoxazole and meropenem resistance in Burkholderia pseudomallei clinical isolates

Burkholderia pseudomallei strains were isolated from a chronic case of melioidosis. Four strains in the 1st sample in 2014. They had divergent morphotypes and divergent antibiotic susceptibilities. Some strains showed resistances to trimethoprim-sulfamethoxazole and fluoroquinolones. In the 2nd clinical sample (2016), only one type of strain was isolated with atypical resistance to meropenem. We performed whole genome sequencing and transcriptomic analysis on the strains isolated during this study to gain further insight into their differences.We thus identified two types of resistance mechanisms occurring in these clinical strains. The first one was an adaptive and transient mechanism that could disappeared in the course of laboratory subcultures. The second one was a mutation in the efflux pump regulator amrR, associated with the overexpression of the related transporter. The activation of such mechanisms may have a clinical impact on the antibiotic treatment. Indeed, the transient nature could lead to an undiagnosed resistance. While efflux overexpression due to mutation leads to an important cross-resistance, reducing the antibiotic effectiveness during treatment.