A novel mechanism for bacterial sporulation based on programmed peptidoglycan degradation

Abstract Many bacteria form spores to endure unfavorable conditions. While Firmicutes generate endospores through cell division, sporulation in non-Firmicutes remains less understood. The Gram-negative bacterium Myxococcus xanthus undergoes sporulation through two distinct mechanisms: rapid sporulation triggered by chemical induction and slow sporulation driven by starvation, both occurring independently of cell division. Instead, these processes depend on the complete degradation of the peptidoglycan (PG) cell wall by lytic transglycosylases (LTGs), with both LtgA and LtgB supporting rapid sporulation and LtgB alone driving slow sporulation. Remarkably, LtgB programs the pace of PG degradation by LtgA during rapid sporulation, ensuring a controlled process that prevents abrupt PG breakdown and the formation of non-resistant pseudospores. In addition to regulation between LTGs, PG degradation is also influenced by its synthesis; cells exhibiting increased muropeptide production often circumvent sporulation. These findings not only reveal novel mechanisms of bacterial sporulation but also shed light on the regulatory network governing PG dynamics.