STARVATION-PHASE-INDUCED AND STATIONARY-PHASE-INDUCED RESISTANCE TO THE ANTIMICROBIAL PEPTIDE POLYMYXIN-B IN SALMONELLA-TYPHIMURIUM IS RPOS(SIGMA(S)) INDEPENDENT AND OCCURS THROUGH BOTH PHOP-DEPENDENT AND PHOP-INDEPENDENT PATHWAYS

A common stress encountered by Salmonella serovars involves exposure t o membrane-permeabilizing antimicrobial peptides and proteins such as defensins, cationic antibacterial proteins, and polymyxins, We wanted to determine if starvation induces cross-resistance to the membrane-pe rmeabilizing antimicrobial peptide polymyxin B (PmB), We report here t hat starved and stationary-phase (Luria-Bertani [LB] medium) cells exh ibited ca. 200- to 1,500-fold-higher (cross-)resistance to a 60-min Pm B challenge than log-phase cells, Genetic analysis indicates that this PmB resistance involves both phoP-dependent acid -independent pathway s, Furthermore, both pathways were sigma(S) independent, indicating th at they are different from other known os-dependent cross-resistance m echanisms, Additionally, both pathways were important for PmB resistan ce early during C starvation and for cells in stationary phase in LB m edium, However, only the phoP-independent pathway was important for P- starvation-induced PmB resistance and the sustained PmB resistance see n in 24-h-C-starved (and N-starved) or stationary-phase cells in LB me dium, The results indicate the presence of an rpoS- and phoP-independe nt pathway important to starvation- and stationary-phase-induced resis tance to membrane-permeabilizing antimicrobial agents.