title: The self-assembly of a cyclic lipopeptides mixture secreted by a B. megaterium strain and its implications on activity against a sensitive Bacillus species.
abstract: Cyclic lipopeptides are produced by a soil Bacillus megaterium strain and several other Bacillus species. In this work, they are detected both in the Bacillus intact cells and the cells culture medium by MALDI-TOF mass spectrometry. The cyclic lipopeptides self-assemble in water media producing negatively charged and large aggregates (300-800 nm of mean hydrodynamic radius) as evaluated by dynamic light scattering and zeta-potential analysis. The aggregate size depends on pH and ionic strength. However, it is not affected by changes in the osmolarity of the outer medium suggesting the absence of an internal aqueous compartment despite the occurrence of low molecular weight phospholipids in their composition as determined from inorganic phosphorus analysis. The activity against a sensitive Bacillus cereus strain was evaluated from inhibition halos and B. cereus lysis. Essential features determining the antibiotic activity on susceptible Bacillus cereus cells are the preserved cyclic moiety conferring cyclic lipopeptides resistance to proteases and the medium pH. The aggregates are inactive per se at the pH of the culture medium which is around 6 or below. The knock out of the sensitive cells only takes place when the aggregates are disassembled due to a high negative charge at pH above 6.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo SP, Brazil.
authors.forename: Manuel T
authors.initials: MT
authors.lastname: Pueyo
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo SP, Brazil.
authors.forename: Bruna A
authors.initials: BA
authors.lastname: Mutafci
authors.affiliation: Departamento de Química-Física, Facultad de Química, Pontificia Universidad Católica de Chile, Macul, Santiago, Chile.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Soto-Arriaza
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo SP, Brazil.
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Mascio
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo SP, Brazil.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Carmona-Ribeiro
mesh_terms: D001409:Bacillus cereus / Q000187:drug effects; D001410:Bacillus megaterium / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D055666:Lipopeptides / Q000096:biosynthesis* / Q000494:pharmacology; D056265:Microbial Interactions / Q000502:physiology*; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000494:pharmacology; D010758:Phosphorus / Q000032:analysis; D066329:Protein Aggregates; D012988:Soil Microbiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D055666:Lipopeptides; D010456:Peptides, Cyclic; D066329:Protein Aggregates; D013501:Surface-Active Agents; D010758:Phosphorus