Proteus mirabilis新的quorum sensing系統及其作為新藥標地開發之研究

Serratia marcescens swarming behavior is thermoregulated, which is characterized by continuous populational surface migration on rich swarming agar surface at 30°C, but not at 37°C. Here we report that environmental temperature shift and fatty acids (especially the saturated fatty acids, SFAs) act as the signal cues regulating S. marcescens swarming through an RssA-RssB two component signal transduction system. SFAs or temperature upshift specifically and negatively regulate S. marcescens swarming, but not swimming motility or the identified factors known to be involved in Serratia swarming, possibly through influencing pattern of cellular fatty acid profile. Fatty acid profile analysis strongly indicates that addition of SFAs at a constant temperature and temperature upshift may either directly or indirectly affect the signaling state of the RssA sensor protein by increasing the incorporation of the high-melting point fatty acids into membrane phospholipid, which subsequently inhibits S. marcescens swarming. The RssA-RssB two-component system mediates this response, as both partners are required to sense and transduce the signals. Expression of a fatty acid synthesis gene fabG and a hemolysin gene shlA is coordinately regulated with swarming by RssA-RssB. Biofilm formation, cell surface structure and extracellular polysaccharide are also affected in the rssA or rssB mutant. Similar phenomena of SFA inhibition are also observed in swarming regulation of Proteus mirabilis and Salmonella typhimurium. Thus, evidence suggests it may be common that membrane fluidity optimization through modulation of cellular fatty acid profile under different physiological culture conditions may subsequently affect two-component signaling pathway, which regulates the composition of cellular fatty acids, expression of virulence factor and multicellular swarming behaviours. This may provide an unidentified and common regulatory circuit for controlling swarming behaviour of not only S. marcescens, but also other swarming bacteria