The antiphage defense system CBASS controls resistance and enables killing by antifolate antibiotics inVibrio cholerae

• DOI: 10.1101/2023.02.27.530311
• Publication Date: 2023-02-28T02:40:10Z
• Authors: Susanne Brenzinger; Martina Airoldi; Adewale Joseph Og...; Ana Rita Brochado
• Keywords: Antifolate

Summary Toxic bacterial modules, in particular toxin-antitoxin (TA) systems, have been long sought-after for their antimicrobial potential, although with limited success 1–6 . Here we show that the cyclic-oligonucleotide-based antiphage signaling system (CBASS), another example of a toxic module, increases sensitivity to well-established antifolate antibiotics, interferes synergy, and ultimately enables lysis by antifolates - classic bacteriostatic Vibrio cholerae We propose molecular mechanism CBASS-antifolate interaction based on onset cyclic-oligonucleotide production nucleotidyltransferase DncV upon folate depletion antifolates. is specific CBASS systems closely related nucleotidyltransferases similar binding. Altogether, our findings illustrate such as defense system, can dramatically impact antibiotic activity, open possibility endogenous metabolites could also act triggers/silencers modules under stress beyond treatment, during phage infection, biofilm formation or disease environments.