GltS regulates biofilm formation in methicillin-resistant Staphylococcus aureus.

GltS regulates biofilm formation in methicillin-resistant Staphylococcus aureus.
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DOI:
10.1038/s42003-022-04239-2
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发表时间:
2022-11-23
影响因子:
5.9
通讯作者:
--
中科院分区:
生物学2区
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基于生物膜的感染是主要的医疗负担。耐甲氧西林金黄色葡萄球菌(MRSA)是引起生物被膜感染的主要病原体之一。虽然生物膜是由许多环境信号诱导的,但负责环境传感的分子并没有很好地描述。在这里,我们研究了离子转运蛋白在生物膜形成中的作用,发现钠-谷氨酸转运蛋白gltS在MRSA生物膜形成中发挥了重要作用。gltS转座子突变体及其互补性表明了这一点。外源谷氨酸的缺乏也促进了JE 2菌株生物膜的形成。外源性谷氨酸摄入的不足加速了内源性谷氨酸/谷氨酰胺的产生,从而导致尿素循环的激活。我们还表明,尿素循环激活是生物膜形成的关键。总之,我们表明,gltS是一个重要的调节生物膜形成的外源性谷氨酸的摄入量控制。针对谷氨酸摄入的干预可能是对抗生物膜的潜在有用方法。由于GltS钠-谷氨酸转运蛋白的缺乏,外源性谷氨酸的摄入受损,促进体外和体内金黄色葡萄球菌生物膜形成增加。
Biofilm-based infection is a major healthcare burden. Methicillin-resistant Staphylococcus aureus (MRSA) is one of major organisms responsible for biofilm infection. Although biofilm is induced by a number of environmental signals, the molecule responsible for environmental sensing is not well delineated. Here we examined the role of ion transporters in biofilm formation and found that the sodium-glutamate transporter gltS played an important role in biofilm formation in MRSA. This was shown by gltS transposon mutant as well as its complementation. The lack of exogenous glutamate also enhanced biofilm formation in JE2 strain. The deficiency of exogenous glutamate intake accelerated endogenous glutamate/glutamine production, which led to the activation of the urea cycle. We also showed that urea cycle activation was critical for biofilm formation. In conclusion, we showed that gltS was a critical regulator of biofilm formation by controlling the intake of exogenous glutamate. An intervention to target glutamate intake may be a potential useful approach against biofilm. Impaired intake of exogenous glutamate, due to deficiency of the GltS sodium-glutamate transporter, promotes increased Staphylococcus aureus biofilm formation in vitro and in vivo.
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