Pseudomonas aeruginosa gshA Mutant Is Defective in Biofilm Formation, Swarming, and Pyocyanin Production.
Pseudomonas aeruginosa gshA Mutant Is Defective in Biofilm Formation, Swarming, and Pyocyanin Production.
复制标题
铜绿假单胞菌gshA突变体在生物膜形成、蜂群和花青素产生方面存在缺陷。
DOI：
10.1128/msphere.00155-18
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发表时间：
2018-04-25
期刊：
影响因子：
4.8
通讯作者：
Rawat M
中科院分区：
文献类型：
--
作者：
Van Laar TA;Esani S;Birges TJ;Hazen B;Thomas JM;Rawat M
铜绿假单胞菌是一种普遍存在的细菌，可引起严重的机会性感染，包括许多医院获得性感染。它也是囊性纤维化患者感染的主要原因。铜绿假单胞菌本质上对多种药物具有耐药性，并且能够形成难以用抗生素根除的生物膜。耐药菌株的数量也在增加，使得铜绿假单胞菌感染的治疗变得非常困难。因此，迫切需要了解铜绿假单胞菌如何引起疾病，以便找到治疗感染的新方法。我们发现主要的氧化还原缓冲剂谷胱甘肽 (GSH) 参与对磷霉素和利福平抗生素的内在耐药性。我们进一步证明 GSH 在铜绿假单胞菌疾病和感染中发挥作用，因为缺乏 GSH 的突变体生物膜形成较少，聚集能力较差，并且产生较少的绿脓素（一种与感染相关的色素）。铜绿假单胞菌是一种普遍存在的革兰氏阴性细菌，可引起严重的机会性感染。该生物体使用的主要氧化还原缓冲剂是谷胱甘肽（GSH）。为了评估 GSH 在铜绿假单胞菌毒力中的作用，使用缺乏 gshA（不产生 GSH）的突变菌株进行了多项分析。与野生型菌株相比，突变菌株在基本培养基中表现出生长延迟。此外，gshA突变体在生物膜和存留细胞形成以及游动和集群运动方面存在缺陷，并且产生的绿脓素（一种关键毒力因子）水平降低。最后，gshA 突变株表现出对甲基紫精（一种氧化还原循环剂）以及硫醇反应性抗生素磷霉素和利福平的敏感性增加。总而言之，这些数据表明 GSH 在铜绿假单胞菌的毒力中发挥着关键作用。重要性 铜绿假单胞菌是一种普遍存在的细菌，可引起严重的机会性感染，包括许多医院获得性感染。它也是囊性纤维化患者感染的主要原因。铜绿假单胞菌本质上对多种药物具有耐药性，并且能够形成难以用抗生素根除的生物膜。耐药菌株的数量也在增加，使得铜绿假单胞菌感染的治疗变得非常困难。因此，迫切需要了解铜绿假单胞菌如何引起疾病，以便找到治疗感染的新方法。我们发现主要的氧化还原缓冲剂谷胱甘肽 (GSH) 参与对磷霉素和利福平抗生素的内在耐药性。我们进一步证明 GSH 在铜绿假单胞菌疾病和感染中发挥作用，因为缺乏 GSH 的突变体生物膜形成较少，聚集能力较差，并且产生较少的绿脓素（一种与感染相关的色素）。
Pseudomonas aeruginosa is a ubiquitous bacterium that can cause severe opportunistic infections, including many hospital-acquired infections. It is also a major cause of infections in patients with cystic fibrosis. P. aeruginosa is intrinsically resistant to a number of drugs and is capable of forming biofilms that are difficult to eradicate with antibiotics. The number of drug-resistant strains is also increasing, making treatment of P. aeruginosa infections very difficult. Thus, there is an urgent need to understand how P. aeruginosa causes disease in order to find novel ways to treat infections. We show that the principal redox buffer, glutathione (GSH), is involved in intrinsic resistance to the fosfomycin and rifampin antibiotics. We further demonstrate that GSH plays a role in P. aeruginosa disease and infection, since a mutant lacking GSH has less biofilm formation, is less able to swarm, and produces less pyocyanin, a pigment associated with infection. Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium that can cause severe opportunistic infections. The principal redox buffer employed by this organism is glutathione (GSH). To assess the role of GSH in the virulence of P. aeruginosa, a number of analyses were performed using a mutant strain deficient in gshA, which does not produce GSH. The mutant strain exhibited a growth delay in minimal medium compared to the wild-type strain. Furthermore, the gshA mutant was defective in biofilm and persister cell formation and in swimming and swarming motility and produced reduced levels of pyocyanin, a key virulence factor. Finally, the gshA mutant strain demonstrated increased sensitivity to methyl viologen (a redox cycling agent) as well as the thiol-reactive antibiotics fosfomycin and rifampin. Taken together, these data suggest a key role for GSH in the virulence of P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa is a ubiquitous bacterium that can cause severe opportunistic infections, including many hospital-acquired infections. It is also a major cause of infections in patients with cystic fibrosis. P. aeruginosa is intrinsically resistant to a number of drugs and is capable of forming biofilms that are difficult to eradicate with antibiotics. The number of drug-resistant strains is also increasing, making treatment of P. aeruginosa infections very difficult. Thus, there is an urgent need to understand how P. aeruginosa causes disease in order to find novel ways to treat infections. We show that the principal redox buffer, glutathione (GSH), is involved in intrinsic resistance to the fosfomycin and rifampin antibiotics. We further demonstrate that GSH plays a role in P. aeruginosa disease and infection, since a mutant lacking GSH has less biofilm formation, is less able to swarm, and produces less pyocyanin, a pigment associated with infection.