Nature Communications, Published online: 05 June 2026; doi:10.1038/s41467-026-73952-x Mutations that cause antibiotic resistance in bacteria can have collateral effects that increase the vulnerability of other pathways to inhibition. Here, Wang et al. use genome-scale CRISPR interference to identify shared and strain-specific vulnerabilities associated with different drug-resistant genotypes in Mycobacterium tuberculosis.