Antibiotic Cycling Reverts Extensive Drug Resistance in Burkholderia multivorans.

Area of Science:

• Microbiology
• Genetics
• Infectious Diseases

Background:

• Antibiotic resistance is a growing global health threat.
• Collateral sensitivity, where resistance to one antibiotic increases susceptibility to another, is a known phenomenon.
• Burkholderia multivorans is an opportunistic pathogen often found in cystic fibrosis patients.

Purpose of the Study:

• To investigate antibiotic collateral sensitivity in extensively drug-resistant Burkholderia multivorans.
• To identify genetic mutations associated with this collateral sensitivity phenotype.

Main Methods:

• Treatment of drug-resistant B. multivorans variants with meropenem or sulfamethoxazole-trimethoprim.
• Phenotypic analysis of antibiotic susceptibility.
• Genomic sequencing to identify mutations.

Main Results:

• Treatment with meropenem or sulfamethoxazole-trimethoprim resulted in increased sensitivity to five different antibiotic classes.
• Identified mutations in resistance-nodulation-division (RND) efflux pump regulators and other uncharacterized pumps.

Conclusions:

• Antibiotic collateral sensitivity is a viable strategy against extensively drug-resistant B. multivorans.
• RND efflux pumps and related regulators are likely involved in mediating this collateral sensitivity phenotype.
• Findings may inform novel therapeutic approaches for multidrug-resistant infections.