Temperate Bacillus phages use arbitrium peptides to coordinate lysis–lysogeny decisions, but whether the mature communication peptide can be sensed directly by Bacillus subtilis and affect its physiology and behavior is unknown. Here we show that the φ3T arbitrium peptide SAIRGA elicits a sequence– and stereochemistry-dependent response in Bacillus subtilis that is strongly expressed in surface-grown colony biofilms but is not accompanied by comparable changes in planktonic growth or static-liquid pellicle morphology. The response persists in the absence of AimR, the canonical arbitrium receptor. Within colonies, SAIRGA alters spatial PtapA activity and increases heat-resistant spore formation without increasing total viable cell yield. Untargeted metabolomics reveals broad dose-dependent remodeling that tracks peptide activity, while program-level proteomics independently converges on late-sporulation and mature-spore-associated states. This study highlights how a phage-derived peptide may act as a signal, enabling the host to pivot toward a survival-focused developmental state.
Bacterial toxin-antitoxin (TA) systems are classically viewed as stress-activated toxic switches. Specifically, ribonucleolytic toxins are thought to indiscriminately cleave RNA to halt cellular growth. We recently showed that the MazF toxin of Bacillus subtilis targets an unusually strict 6bp RNA cleavage sequence, but the implications of this stringent specificity were unknown. Here, we demonstrate that the MazEF system functions as a non-lethal post-transcriptional regulator in B. subtilis. Using a specialized single cell fluorescent reporter and transcriptome profiling, we show that MazF is uniformly activated across the population upon entry into the stationary phase, where it cleaves a narrow mRNA regulon to reshape gene expression. Rather than inhibiting growth, MazF activation tunes down the Spo0A stress response by repressing the mRNA level of its kinases. Reduced stress leads to an adaptive shortening of the lag phase upon nutrient replenishment. Furthermore, MazEF’s structural architecture, cleavage specificity, and impact on growth recovery are highly conserved across Gram-positive bacteria. Altogether, our findings redefine a paradigmatic toxin as a precision global mRNA stress regulator that primes cells for rapid regrowth. Graphical abstract
Regev Frenkel, Shira Omer, Tom Borenstein et al.· bioRxiv· 0 citations
