Modulation of Swarming and Virulence by Fatty Acids through the RsbA Protein inProteus mirabilis

Abstract

After sensing external signals, Proteus mirabilis undergoes a multicellular behavior called swarming which is coordinately regulated with the expression of virulence factors. Here we report that exogenously added fatty acids could act as signals to regulate swarming in P. mirabilis. Specifically, while oleic acid enhanced swarming, some saturated fatty acids, such as lauric acid, myristic acid, palmitic acid, and stearic acid, inhibited swarming. We also found that expression of hemolysin, which has been shown to be coordinately regulated with swarming, was also inhibited by the above saturated fatty acids. Previously we identified a gene, rsbA, which may encode a histidine-containing phosphotransmitter of the bacterial two-component signaling system and act as a repressor of swarming and virulence factor expression in P. mirabilis. We found that while myristic acid, lauric acid, and palmitic acid exerted their inhibitory effect on swarming and hemolysin expression through an RsbAdependent pathway, the inhibition by stearic acid was mediated through an RsbA-independent pathway. Biofilm formation and extracellular polysaccharide (EPS) production play an important role in P. mirabilis infection. We found that RsbA may act as a positive regulator of biofilm formation and EPS production. Myristic acid was found to slightly stimulate biofilm formation and EPS production, and this stimulation was mediated through an RsbA-dependent pathway. Together, these data suggest that fatty acids may act as environmental cues to regulate swarming and virulence in P. mirabilis and that RsbA may play an important role in this process.

Production of Quorum Sensing Inhibitors in Growing Onion Bulbs Infected withPseudomonas aeruginosaE (HQ324110)

“…Data of current research indicate that myristic acid and pantolactone may act as negative signals for regulation of bacterial virulence. Our finding supports the work of Liaw et al [41] who found that some saturated fatty acids inhibited swarming and virulence factor expression in Proteus mirabilis , Serratia marcescens , and Salmonella enterica . Hentzer et al [42] demonstrated that the Pseudomonas aeruginosa communication systems can be blocked by halogenated furanone compound.…”

Pathogenesis of Proteus mirabilis Infection

“…Logically, regulators of the above biofilm factors, such as the RcsBCD phosphorelay (RcsD is also known as RsbA) (140, 177, 279) and RNA chaperone Hfq (164), control biofilm formation. Surface hydrophobicity, mediated by lipopolysaccharide (LPS) (53, 280, 281) and capsular polysaccharides (282–284), influence both initial surface colonization and biofilm maturation.…”

Proteus mirabilisand Urinary Tract Infections

“…During swarming, this mutant expresses higher levels of flagellin, as well as other swarming co-regulated virulence factors including hemolysin, protease, and urease (105). An RsbA-mediated pathway may involve sensing of saturated fatty acids to determine a tendency toward swarming or biofilm formation (107). That is, in the presence of specific fatty acids (myristic acid, lauric acid, palmitic acid), swarming behavior is inhibited while biofilm formation and extracellular polysaccharide production is enhanced.…”