title: Cationic antimicrobial peptides elicit a complex stress response in Bacillus subtilis that involves ECF-type sigma factors and two-component signal transduction systems.
abstract: Stress responses of Bacillus subtilis to membrane-active cationic antimicrobial peptides were studied. Global analysis of gene expression by DNA macroarray showed that peptides at a subinhibitory concentration activated numerous genes. A prominent pattern was the activation of two extracytoplasmic function sigma factor regulons, SigW and SigM. Two natural antimicrobial peptides, LL-37 and PG-1, were weak activators of SigW regulon genes, whereas their synthetic analogue poly-L-lysine was clearly a stronger activator of SigW. It was demonstrated for the first time that LL-37 is a strong and specific activator of the YxdJK two-component systems, one of the three highly homologous two-component systems sensing antimicrobial compounds. YxdJK regulates the expression of the YxdLM ABC transporter. The LiaRS (YvqCE) TCS was also strongly activated by LL-37, but its activation is not LL-37 specific, as was demonstrated by its activation with PG-1 and Triton X-100. Other strongly LL-37-induced genes included yrhH and yhcGHI. Taken together, the responses to cationic antimicrobial peptides revealed highly complex regulatory patterns and induction of several signal transduction pathways. The results suggest significant overlap between different stress regulons and interdependence of signal transduction pathways mediating stress responses.
authors.affiliation: Vaccine Development Laboratory, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
authors.forename: Milla
authors.initials: M
authors.lastname: Pietiäinen
authors.affiliation: Vaccine Development Laboratory, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
authors.forename: Marika
authors.initials: M
authors.lastname: Gardemeister
authors.affiliation: Vaccine Development Laboratory, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Mecklin
authors.affiliation: Vaccine Development Laboratory, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
authors.forename: Soile
authors.initials: S
authors.lastname: Leskelä
authors.affiliation: Vaccine Development Laboratory, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Sarvas
authors.affiliation: Vaccine Development Laboratory, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
authors.forename: Vesa P
authors.initials: VP
authors.lastname: Kontinen
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D018869:Heat-Shock Response; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D020543:Proteome; D012808:Sigma Factor