Novel genes involved in the resistance of antimicrobial peptides in Salmonella enterica

MARTÍN ESPARIZ; JULIETA BARCHIESI; FERNANDO C. SONCINI

San Carlos de Bariloche, Argentina.

Congreso; Argentine Society for Biochemistry and Molecular Biology XXXIX Annual Meeting. Biophysical society of Argentina XXXII Annual Meeting. Bariloche Protein Symposium.; 2003

Sociedad Argentina de Bioquímica y Biología Molecular y Sociedad Argentina de Biofísica.

Studies that provided new insight into the relationship between the host and their pathogens are necessary to solve the growing problem of resistance to conventional antibiotic. The bacterial genes involved in 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 Salmonella enterica serovar Typhimurium it has been demonstrated that resistance to antimicrobial peptides is essential to colonize the tissues of the infected host. We perform a genetic analysis of an operon that increased the bacterial resistance to the antimicrobial peptide protamine and cecropin P1 and that is essential for the virulence behaviour of Salmonella. On the other hand and interestingly, this mutant showed increased resistence to polimixina B. The LPS extracted from the MudJ insertional mutant showed an electrophoresis pattern similar to the one that characterizes PmrA constitutive (PmrAc) polymyxin resistance strains. Nevertheless, expression of this gene was independent of either PmrA-PmrB, or PhoP-PhoQ. Surprisingly, the mutant do not loss the abilities to replicate in macrophages, indicating that resistance to antimicrobial peptides is not associated to macrophage survival. Current experiments show the crucial rol of antimicrobial peptides outside the macrophage and explain the different pathologies caused by a particular strain of Salmonella to different host. Our analysis will broaden the knowledge of the actions taken by Salmonella to resist the initial host antimicrobial assault in order to prosper in the infection process.