Rhodomyrtone decreases Staphylococcus aureus SigB activity during exponentially growing phase and inhibits haemolytic activity within membrane vesicles
Rhodomyrtone decreases Staphylococcus aureus SigB activity during exponentially growing phase and inhibits haemolytic activity within membrane vesicles
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DOI：
10.1016/j.micpath.2018.12.019
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发表时间：
2019-03-01
影响因子：
3.8
通讯作者：
Voravuthikunchai, Supayang P.
中科院分区：
文献类型：
--
作者：
Mitsuwan, Watcharapong;Jimenez-Munguia, Irene;Voravuthikunchai, Supayang P.
Sigma因子B控制包括毒力因子在内的金黄色葡萄球菌基因的表达，并通过膜泡的产生在细菌分泌系统中发挥作用。抑制SigB可以减弱SigB依赖的毒力和分泌系统。本研究的目的是确定玫瑰内酯对SigB的影响以及与SigB相关的毒力因子。该药对67株临床分离的耐甲氧西林金黄色葡萄球菌的最小抑菌浓度(MIC)和最小杀菌浓度(MBC)为0.25~8mU g/ml，与万古霉素相近。将荧光素酶基因融合到asp23的SigB依赖启动子中，用红景天处理细菌3h后，SigB活性下降5倍，在指数生长的细胞中，红景天以浓度依赖的方式显著降低SigB活性(P<；0.05)。此外，SIGB突变体比野生型突变体和yabJ-spoVG突变体对罗丹草酮浓度的增加更为敏感。与yabJ-spVG突变体和野生型相比，0.625 mU g/ml的红内酯对sigb突变体的生长抑制约99%。0.5倍最低抑菌浓度的柔红花内酯可显著减少细菌细胞膜上的囊泡(P<；0.05)。在罗丹香酮处理的膜小泡中检测到溶血活性降低。结果表明，金黄色葡萄球菌在指数生长期对SigB活性有抑制作用，膜泡内溶血活性也受到抑制。
Sigma factor B (SigB) controls the expression of Staphylococcus aureus genes including virulence factors and plays a role in the bacterial secretion system through membrane vesicle production. Inhibition of SigB could attenuate SigB dependent virulence and secretion system. The objective of this study was to determine the effects of rhodomyrtone on SigB and virulence factors related to SigB. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values of rhodomyrtone against 67 clinical methicillin-resistant S. aureus isolates were 0.25-8 mu g/ml, which were similar to those of vancomycin. Using luciferase gene fused to SigB dependent promoters of asp23, five time reduction in SigB activity was observed when the bacteria were treated with rhodomyrtone for 3 h. Rhodomyrtone significantly reduced SigB activity in a concentration dependent manner in exponentially growing cells (P < 0.05). In addition, sigB mutant was more sensitive towards increasing concentrations of rhodomyrtone than the wild type and yabJ-spoVG mutant. Rhodomyrtone at 0.625 mu g/ml reduced the growth of sigB mutant by approximately 99%, compared with the yabJ-spoVG mutant and the wild type. Membrane vesicles were significantly reduced in the bacterial cells when treated with 0.5 x MIC rhodomyrtone (P < 0.05). Decreased haemolytic activity was detected within rhodomyrtone-treated membrane vesicles. The results indicated that rhodomyrtone inhibited S. aureus SigB activity during exponentially growing phase and inhibited haemolytic activity within membrane vesicles.