title: Against the mainstream: the membrane-associated type I toxin BsrG from Bacillus subtilis interferes with cell envelope biosynthesis without increasing membrane permeability.
abstract: Toxin-antitoxin loci, which encode a toxic protein alongside with either RNA or a protein able to counteract the toxicity, are widespread among archaea and bacteria. These loci are implicated in persistence, and as addiction modules to ensure stable inheritance of plasmids and phages. In type I toxin-antitoxin systems, a small RNA acts as an antitoxin, which prevents the synthesis of the toxin. Most type I toxins are small hydrophobic membrane proteins generally assumed to induce pores, or otherwise permeabilise the cytoplasmic membrane and, as a result, induce cell death by energy starvation. Here we show that this mode of action is not a conserved property of type I toxins. The analysis of the cellular toxicity caused by Bacillus subtilis prophage SPβ-encoded toxin BsrG revealed that, surprisingly, it neither dissipates membrane potential nor affects cellular ATP-levels. In contrast, BsrG strongly interferes with the cell envelope biosynthesis, causes membrane invaginations together with delocalisation of the cell wall synthesis machinery and triggers autolysis. Furthermore, efficient inhibition of protein biosynthesis is observed. These findings question the simplistic assumption that small membrane targeting toxins generally act by permeabilising the membrane.
authors.affiliation: Friedrich-Schiller-Universität Jena, Biologisch-Pharmazeutische Fakultät, AG Bakteriengenetik, Philosophenweg 12, Jena, D-07743, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Jahn
authors.affiliation: Friedrich-Schiller-Universität Jena, Biologisch-Pharmazeutische Fakultät, AG Bakteriengenetik, Philosophenweg 12, Jena, D-07743, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Brantl
authors.affiliation: Newcastle University, Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Strahl
mesh_terms: D017103:Bacillus Phages / Q000235:genetics; D001412:Bacillus subtilis / Q000166:cytology / Q000235:genetics* / Q000378:metabolism* / Q000821:virology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002463:Cell Membrane Permeability; D002473:Cell Wall / Q000378:metabolism / Q000648:ultrastructure; D015964:Gene Expression Regulation, Bacterial; D039002:Prophages / Q000235:genetics; D014176:Protein Biosynthesis
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins