Journal Article

SEDS proteins are a widespread family of bacterial cell wall polymerases

Bernhardt, Thomas G., Robins, William P., Meeske, Alexander J., Kahne, Daniel, Kruse, Andrew C., Uehara, Tsuyoshi, Rudner, David Z., Walker, Suzanne, Mekalanos, John J., Riley, Eammon P.

2016

Overview

Elongation of rod-shaped bacteria is mediated by a dynamic peptidoglycan-synthetizing machinery called the Rod complex. Here we report that, in Bacillus subtilis , this complex is functional in the absence of all known peptidoglycan polymerases. Cells lacking these enzymes survive by inducing an envelope stress response that increases the expression of RodA, a widely conserved core component of the Rod complex. RodA is a member of the SEDS (shape, elongation, division and sporulation) family of proteins, which have essential but ill-defined roles in cell wall biogenesis during growth, division and sporulation. Our genetic and biochemical analyses indicate that SEDS proteins constitute a family of peptidoglycan polymerases. Thus, B. subtilis and probably most bacteria use two distinct classes of polymerase to synthesize their exoskeleton. Our findings indicate that SEDS family proteins are core cell wall synthases of the cell elongation and division machinery, and represent attractive targets for antibiotic development. SEDS proteins are core peptidoglycan polymerases involved in bacterial cell wall elongation and division. SEDS proteins key to bacterial cell wall integrity It has been generally accepted that the cell wall peptidoglycans of the bacterial exoskeleton are synthesized by penicillin binding proteins (PBPs) known as class A PBPs. Now, using genetic manipulation, phylogenetic analysis and functional experiments in Bacillus subtilis , David Rudner and colleagues have identified SEDS family proteins as the main peptidoglycan polymerases more broadly conserved than class A PBPs. Specifically in B. subtilis , they show that the SEDS protein RodA, a widely conserved component of the Rod complex involved in elongation of rod-shaped bacteria, acts with class B PBPs as the core cell wall synthase of the cell elongation and division machinery. The authors conclude that B. subtilis and probably most bacteria use two distinct classes of polymerases to synthesize their exoskeleton. This work also suggests that SEDS family proteins should be attractive targets for antibiotic development.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 14/63 / 38/70 / 631/326/1320 / 631/326/41/1969 / 631/326/88 / 82/83 / Anti-Bacterial Agents - pharmacology / Antigens / Bacillus subtilis / Bacillus subtilis - cytology / Bacillus subtilis - drug effects / Bacillus subtilis - enzymology / Bacillus subtilis - growth & development / Bacteria / Bacterial cell walls / Bacterial infections / Bacterial Proteins - chemistry / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Biosynthesis / Cell Division / Cell Wall - chemistry / Cell Wall - metabolism / Drug Design / Drug Resistance, Bacterial - drug effects / Enzymes / Humanities and Social Sciences / Lipids / multidisciplinary / Mutation / Oligosaccharides - pharmacology / Penicillin / Penicillin-Binding Proteins - classification / Penicillin-Binding Proteins - genetics / Penicillin-Binding Proteins - metabolism / Peptides / Peptidoglycan - biosynthesis / Peptidoglycan Glycosyltransferase - chemistry / Peptidoglycan Glycosyltransferase - genetics / Peptidoglycan Glycosyltransferase - metabolism / Phenotype / Physiological aspects / Polymerization / Proteins / Science