Molecular analysis of mutant strains sensitive to antimicrobial peptides in Salmonella enterica.

MARTÍN ESPARIZ; FERNANDO C. SONCINI

Carlos Paz, Córdoba, Argentina.

Congreso; Argentine Society for Biochemistry and Molecular Biology XXXVIII Annual Meeting.; 2002

Sociedad Argentina de Bioquímica y Biología molecular.

  The knowledge of the mechanisms that mediate the resistance to microbicidal peptides in pathogenic bacteria is essential to understand those tools used throughout the infective process to colonize the host and to evade its innate immune response. Because the bacterial genes involved in the resistance to antimicrobial peptides are ideal targets for the action of novel antibacterial agents, the detailed knowledge of their mechanism of action will entail the development of alternative therapies. In an attempt to identify novel genes required for resistance to antimicrobial peptides in Salmonella enterica serovar Typhimurium (S. enterica), we screened 20,000 random MudJ transposon insertion mutants for their increase sensitivity to protamine, and isolated 21 that, after their retransduction were more susceptible than the wild type strain. We determined the presence of new genes involved in the resistance to this peptide by a direct genomic DNA sequencing using a primer homologous to the transposon attL end. We identified the presence of insertions in genes involved in the regulation of the cellular response to extracytoplasmic stress; in the synthesis of a siderophore; in the synthesis of lipid A; in the synthesis or modification of surface structures; as well as in genes previously determined to be involved in resistance to antimicrobial peptides.