Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.

Bacteria exhibit an evolutionary trade-off through their development of collateral sensitivity (CS) which allows them to resist one antibiotic while becoming more vulnerable to another. This vulnerability offers a compelling therapeutic opportunity by selecting against resistant isolates. Laboratory evolution studies, genome sequencing, deep mutagenesis and use of artificial intelligence and machine learning can design the bespoke strategy against multi-drug-resistant bacteria. This review discusses about recent studies that are rationally designed to harness this evolutionary trade-off for the development of alternative antimicrobial strategies. The translational barriers to the clinical implementation of CS are addressed and evidence-based design principles for optimization of CS-guided therapy are discussed.