Reciprocal antibiotic collateral sensitivity in Burkholderia multivorans

Area of Science:

• Microbiology
• Genetics
• Pharmacology

Background:

• Antibiotic resistance is a growing global health threat.
• Collateral sensitivity (CS) describes decreased resistance to one antibiotic upon developing resistance to another.
• Understanding CS networks can inform novel treatment strategies.

Purpose of the Study:

• To identify reciprocal collateral sensitivity (CS) networks and candidate genes in Burkholderia multivorans.
• To investigate the genetic basis of CS in this bacterium.
• To explore the potential of CS for long-term antibiotic treatment strategies.

Main Methods:

• Bacterial evolution: Burkholderia multivorans was evolved for resistance to six different antibiotics.
• Antibiogram analysis: Evolved strains were tested for sensitivity to various antibiotics to identify CS and cross-resistance.
• Whole-genome sequencing: Genetic mutations in resistant strains were correlated with observed CS patterns.

Main Results:

• CS interactions were observed in 170 of 279 evolved strains.
• CS patterns clustered based on whether the antibiotic was a beta-lactam.
• Reciprocal CS pairs were found in at least 25% of evolved strains.
• Whole-genome sequencing indicated that CS is likely due to a combination of mutations, not a single gene.

Conclusions:

• Reciprocal collateral sensitivity networks were identified in Burkholderia multivorans.
• CS in B. multivorans is polygenic, resulting from multiple mutations.
• The findings support a treatment strategy involving switching between reciprocal CS antibiotics to manage chronic infections indefinitely.