Rasch Maria, Kastbjerg Vicky Gaedt, Bruhn Jesper Bartholin, Dalsgaard Inger, Givskov Michael, Gram Lone
Danish Institute for Fisheries Research, Department of Seafood Research, Technical University of Denmark, Søltofts Plads bldg. 221, 2800 Kgs. Lyngby, Denmark.
Dis Aquat Organ. 2007 Dec 13;78(2):105-13. doi: 10.3354/dao01865.
Many pathogens control production of virulence factors by self-produced signals in a process called quorum sensing (QS). We demonstrate that acyl homoserine lactone (AHL) signals, which enable bacteria to express certain phenotypes in relation to cell density, are produced by a wide spectrum of Aeromonas salmonicida strains. All 31 typical strains were AHL producers as were 21 of 26 atypical strains, but on a strain population basis, production of virulence factors such as protease, lipase, A-layer or pigment did not correlate with the production and accumulation of AHLs in the growth medium. Pigment production was only observed in broth under highly aerated conditions. Quorum sensing inhibitors (QSIs) are compounds that specifically block QS systems without affecting bacterial growth and 2 such compounds, sulphur-containing AHL-analogues, reduced production of protease in a typical strain of Aeromonas salmonicida. The most efficient compound N-(heptylsulfanylacetyl)-L-homoserine lactone (HepS-AHL), reduced protease production by a factor of 10. Five extracellular proteases were detected on gelatin-containing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gels and 3 of these were completely down regulated by HepS-AHL. Hence, QSIs can curb virulence in some strains and could potentially be pursued as bacterial disease control measures in aquaculture.
许多病原体通过一种称为群体感应(QS)的过程,利用自身产生的信号来控制毒力因子的产生。我们证明,酰基高丝氨酸内酯(AHL)信号能使细菌根据细胞密度表达某些表型,多种杀鲑气单胞菌菌株均可产生该信号。所有31株典型菌株均为AHL产生菌,26株非典型菌株中的21株也是如此,但从菌株群体角度来看,蛋白酶、脂肪酶、A层或色素等毒力因子的产生与生长培养基中AHL的产生和积累并无关联。仅在高通气条件下的肉汤中观察到色素产生。群体感应抑制剂(QSIs)是一类能特异性阻断QS系统而不影响细菌生长的化合物,两种此类化合物,即含硫的AHL类似物,可降低杀鲑气单胞菌典型菌株中蛋白酶的产生。最有效的化合物N-(庚基硫烷基乙酰基)-L-高丝氨酸内酯(HepS-AHL)可使蛋白酶产量降低10倍。在含明胶的十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)凝胶上检测到5种细胞外蛋白酶,其中3种被HepS-AHL完全下调。因此,QSIs可抑制某些菌株的毒力,并有可能作为水产养殖中控制细菌性疾病的措施加以应用。