title: Direct surfactin-gramicidin S antagonism supports detoxification in mixed producer cultures of Bacillus subtilis and Aneurinibacillus migulanus.
abstract: Antibiotic production as a defence mechanism is a characteristic of a wide variety of organisms. In natural evolutionary adaptation, cellular events such as sporulation, biofilm formation and resistance to antibiotics enable some micro-organisms to survive environmental and antibiotic stress conditions. The two antimicrobial cyclic peptides in this study, gramicidin S (GS) from Aneurinibacillus migulanus and the lipopeptide surfactin (Srf) from Bacillus subtilis, have been shown to affect both membrane and intercellular components of target organisms. Many functions, other than that of antimicrobial activity, have been assigned to Srf. We present evidence that an additional function may exist for Srf, namely that of a detoxifying agent that protects its producer from the lytic activity of GS. We observed that Srf producers were more resistant to GS and could be co-cultured with the GS producer. Furthermore, exogenous Srf antagonized the activity of GS against both Srf-producing and non-producing bacterial strains. A molecular interaction between the anionic Srf and the cationic GS was observed with circular dichroism and electrospray MS. Our results indicate that the formation of an inactive complex between GS and Srf supports resistance towards GS, with the anionic Srf forming a chemical barrier to protect its producer. This direct detoxification combined with the induction of protective stress responses in B. subtilis by Srf confers resistance toward GS from A. migulanus and allows survival in mixed cultures.
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa.
authors.forename: Marina
authors.initials: M
authors.lastname: Rautenbach
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa.
authors.forename: Hans André
authors.initials: HA
authors.lastname: Eyéghé-Bickong
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa.
authors.forename: Nicolas Maré
authors.initials: NM
authors.lastname: Vlok
authors.affiliation: Department of Biochemistry and LCMS-Central Analytical Facility, Science Faculty, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa.
authors.forename: Marietjie
authors.initials: M
authors.lastname: Stander
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa.
authors.forename: Abré
authors.initials: A
authors.lastname: de Beer
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000898:Antibiosis; D056449:Bacillales / Q000187:drug effects* / Q000378:metabolism; D002942:Circular Dichroism; D024881:Drug Resistance, Bacterial; D006096:Gramicidin / Q000378:metabolism / Q000493:pharmacokinetics*; D008658:Inactivation, Metabolic; D055666:Lipopeptides / Q000378:metabolism / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000900:Anti-Bacterial Agents; D055666:Lipopeptides; D010456:Peptides, Cyclic; D006096:Gramicidin; C009365:surfactin peptide