Pseudomonas aeruginosa defense systems against microbicidal oxidants.
Pseudomonas aeruginosa defense systems against microbicidal oxidants.
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DOI：
10.1111/mmi.13768
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发表时间：
2017-11
影响因子：
3.6
通讯作者：
Jakob U
中科院分区：
文献类型：
--
作者：
Groitl B;Dahl JU;Schroeder JW;Jakob U
控制粘膜屏障上皮上细菌定殖的最丰富的氧化剂是次氯酸（HOCl）、次溴酸（HOBr）和次硫氰酸（HOSCN）。所有这三种氧化剂都具有高度的抗菌性，但对它们的相对功效、各自的细胞靶点或它们在细菌中引起的具体反应知之甚少。为了解决这些重要的问题，我们直接测试了有毒的铜绿假单胞菌菌株PA 14上的各个氧化剂。我们发现HOCl和HOBr几乎可互换地起作用，比活跃生长的细菌更显著地影响非生长的细菌培养物，并引发类似的应激反应，包括热休克反应。HOSCN处理明显不同，主要影响活跃生长的PA 14，并引起暗示膜损伤的应激反应。然而，这三种氧化剂的共同点是它们都能引起大量的蛋白质聚集。这种效应在缺乏多磷酸盐（一种新认识的化学伴侣）的菌株中变得特别明显。用FDA批准的抗炎药物美沙拉嗪治疗PA14，最近已被证明可以减弱多种细菌中的聚P产生，有效地降低了PA14对所有三种氧化剂的抗性，这表明我们已经在铜绿假单胞菌中发现了一种新的靶向防御系统。多磷酸盐的积累是铜绿假单胞菌通过减少氧化蛋白的解折叠和聚集来响应和抵抗宿主诱导的抗微生物氧化剂产生的通用策略。由FDA批准的药物美沙拉嗪引起的多磷酸盐产生的损害使病原体对所有三种生理氧化剂敏感，使得美沙拉嗪可能是一种有吸引力的新治疗选择，以提高内源性宿主防御系统杀死抗应激微生物的能力。
The most abundant oxidants controlling bacterial colonization on mucosal barrier epithelia are hypochlorous acid (HOCl), hypobromous acid (HOBr), and hypothiocyanous acid (HOSCN). All three oxidants are highly antimicrobial but little is known about their relative efficacies, their respective cellular targets, or what specific responses they elicit in bacteria. To address these important questions, we directly tested the individual oxidants on the virulent Pseudomonas aeruginosa strain PA14. We discovered that HOCl and HOBr work almost interchangeably, impacting non-growing bacterial cultures more significantly than actively growing bacteria, and eliciting similar stress responses, including the heat shock response. HOSCN treatment is distinctly different, affecting primarily actively growing PA14, and evoking stress responses suggestive of membrane damage. What all three oxidants have in common, however, is their ability to cause substantial protein aggregation. This effect became particularly obvious in strains lacking polyphosphate, a newly recognized chemical chaperone. Treatment of PA14 with the FDA-approved anti-inflammatory drug mesalamine, which has recently been shown to attenuate polyP production in a wide range of bacteria, effectively decreased the resistance of PA14 towards all three oxidants, suggesting that we have discovered a novel, targetable defense system in P. aeruginosa. Accumulation of polyphosphate serves as the universal strategy of P. aeruginosa to respond to and resist the host-induced production of antimicrobial oxidants by reducing oxidative protein unfolding and aggregation. Impairment of polyphosphate production caused by the FDA-approved drug mesalamine sensitizes the pathogen towards all three physiological oxidants making mesalamine potentially an attractive new treatment option to improve the ability of the endogenous host defense systems to kill stress-resistant microbes.
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影响因子：
14.8
作者：
Hmelo LR;Borlee BR;Almblad H;Love ME;Randall TE;Tseng BS;Lin C;Irie Y;Storek KM;Yang JJ;Siehnel RJ;Howell PL;Singh PK;Tolker-Nielsen T;Parsek MR;Schweizer HP;Harrison JJ
通讯作者：
Harrison JJ
影响因子：
3.3
作者：
Chandler, J. D.;Day, B. J.
通讯作者：
Day, B. J.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
7
作者：
Chi, Bui Khanh;Gronau, Katrin;Antelmann, Haike
通讯作者：
Antelmann, Haike
影响因子：
4.4
作者：
Ceragioli, Mara;Mols, Maarten;Abee, Tjakko
通讯作者：
Abee, Tjakko