Starvation- 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 -independent pathways.
A common stress encountered by Salmonella serovars involves exposure to 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-permeabilizing antimicrobial peptide polymyxin B (PmB). We report here that starved and stationary-phase (Luria-Bertani [LB] medium) cells exhibited ca. 200- to 1,500-fold-higher (cross-)resistance to a 60-min PmB challenge than log-phase cells. Genetic analysis indicates that this PmB resistance involves both phoP-dependent and -independent pathways. Furthermore, both pathways were sigma(S) independent, indicating that they are different from other known sigma(S) -dependent cross-resistance mechanisms. Additionally, both pathways were important for PmB resistance early during C starvation and for cells in stationary phase in LB medium. However, only the phoP-independent pathway was important for P-starvation-induced PmB resistance and the sustained PmB resistance seen in 24-h-C-starved (and N-starved) or stationary-phase cells in LB medium. The results indicate the presence of an rpoS- and phoP-independent pathway important to starvation- and stationary-phase-induced resistance to membrane-permeabilizing antimicrobial agents.
McLeod
G I
GI
Department of Biomedical Sciences, University of South Alabama, Mobile, Alabama 36688-0002, USA.
Spector
M P
MP
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002244:Carbon / Q000494:pharmacology; D002453:Cell Cycle; D003470:Culture Media / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D010710:Phosphates / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D012808:Sigma Factor / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D010710:Phosphates; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; C061064:PhoP protein, Bacteria; D002244:Carbon; D011112:Polymyxin B