Cyclic di-AMP inhibits <i>Listeria monocytogenes</i> thymineless death during infection.

ABSTRACT: Antifolate antibiotics are used to treat meningitis and refractory listeriosis caused by drug-resistant Listeria monocytogenes (Lm). Their bactericidal activity is attributed to the deactivation of thymidylate synthase (ThyA), which subsequently induces bacterial cell death when thymidine is depleted, a process known as thymineless death (TLD). Despite decades of study, the mechanisms of TLD, especially during infection, remain unclear. Cyclic di-AMP (c-di-AMP), a common bacterial second messenger that regulates bacterial stress responses, is elevated in response to antifolate antibiotics. In this study, we found that elevated c-di-AMP is required to inhibit TLD in Lm. Conversely, reducing c-di-AMP levels in the ΔthyA mutant led to increased bacterial cell death

SUBMITTER: Leeming JP 

PROVIDER: S-EPMC12802241 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature