Control of bacterial cell wall autolysins by peptidoglycan crosslinking mode

• Published in: Nature communications 2024-09, Vol.15 (1), p.7937-11, Article 7937
• Main Authors: Alvarez, Laura, Hernandez, Sara B., Torrens, Gabriel, Weaver, Anna I., Dörr, Tobias, Cava, Felipe
• Format: Article
• Language: English
• Subjects: 14/63; 45/70; 49; 631/326/1320; 631/326/41; 631/326/41/2528; 631/45/607; 82/16; 82/83; Autolysins; Bacillus subtilis - metabolism; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Cell Wall - metabolism; Cell walls; Crosslinking; Environmental impact; Enzymes; Escherichia coli - metabolism; External pressure; Glycan; Glycosyltransferases - metabolism; Homeostasis; Humanities and Social Sciences; Immunogenicity; multidisciplinary; N-Acetylmuramoyl-L-alanine Amidase - chemistry; N-Acetylmuramoyl-L-alanine Amidase - metabolism; Peptidoglycan - metabolism; Peptidoglycans; Polymers; Regulatory mechanisms (biology); Saccule; Science; Science (multidisciplinary); Turgor
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52325-2

To withstand their internal turgor pressure and external threats, most bacteria have a protective peptidoglycan (PG) cell wall. The growth of this PG polymer relies on autolysins, enzymes that create space within the structure. Despite extensive research, the regulatory mechanisms governing these PG-degrading enzymes remain poorly understood. Here, we unveil a novel and widespread control mechanism of lytic transglycosylases (LTs), a type of autolysin responsible for breaking down PG glycan chains. Specifically, we show that LD-crosslinks within the PG sacculus act as an inhibitor of LT activity. Moreover, we demonstrate that this regulation controls the release of immunogenic PG fragments and provides resistance against predatory LTs of both bacterial and viral origin. Our findings address a critical gap in understanding the physiological role of the LD-crosslinking mode in PG homeostasis, highlighting how bacteria can enhance their resilience against environmental threats, including phage attacks, through a single structural PG modification. The regulatory mechanisms governing peptidoglycan-degrading autolysins remain poorly understood. In this work, Alvarez et al . show that lytic transglycosylase activity is inhibited by LD-crosslinks in Vibrio cholerae and other bacteria, providing resistance against predatory enzymes of both bacterial and viral origin.