The Antimicrobial Activity of a Carbon Monoxide Releasing Molecule (EBOR-CORM-1) Is Shaped by Intraspecific Variation within Pseudomonas aeruginosa Populations.
The Antimicrobial Activity of a Carbon Monoxide Releasing Molecule (EBOR-CORM-1) Is Shaped by Intraspecific Variation within Pseudomonas aeruginosa Populations.
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DOI：
10.3389/fmicb.2018.00195
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发表时间：
2018
影响因子：
5.2
通讯作者：
Friman VP
中科院分区：
文献类型：
--
作者：
Flanagan L;Steen RR;Saxby K;Klatter M;Aucott BJ;Winstanley C;Fairlamb IJS;Lynam JM;Parkin A;Friman VP
一氧化碳释放分子（CORM）已被建议作为一种新的合成类抗菌剂来治疗细菌感染。在这里，我们利用了一种新的EBOR-CORM-1（[NEt 4][MnBr 2（CO）4]）能够水触发CO释放，并测试了其对一组临床铜绿假单胞菌菌株的疗效，这些菌株在感染相关的毒力性状上不同。我们发现，虽然EBOR-CORM-1以浓度依赖性方式有效清除铜绿假单胞菌菌株PAO 1的嗜酸性和生物膜细胞，但这种作用不太清楚，并且在不同的铜绿假单胞菌囊性纤维化（CF）肺分离株之间变化很大。虽然在CORM应用8小时后观察到细胞生长减少，但在24小时后观察到细胞密度和生物膜量没有影响或甚至略有增加。这种变化可以部分解释细菌毒力性状的差异：虽然CF分离株显示出减弱的体内毒力和生长相比，菌株PAO 1，他们形成了更多的生物膜，这可能有可能保护他们从CORM。尽管在体内蜡螟急性感染模型中没有观察到针对分离物子集的明确治疗益处，但与针对更均匀的单一分离物培养群体的功效相比，EBOR-CORM-1在减少具有种内变异的CF分离物共培养群体的生长方面更有效。总之，这些结果表明，CORM可以有效地控制自然慢性CF感染的典型遗传多样性铜绿假单胞菌种群，并且如果仅针对克隆细菌种群进行测试，则可能无法观察到某些抗生素的潜在益处。
Carbon monoxide releasing molecules (CORMs) have been suggested as a new synthetic class of antimicrobials to treat bacterial infections. Here we utilized a novel EBOR-CORM-1 ([NEt4][MnBr2(CO)4]) capable of water-triggered CO-release, and tested its efficacy against a collection of clinical Pseudomonas aeruginosa strains that differ in infection-related virulence traits. We found that while EBOR-CORM-1 was effective in clearing planktonic and biofilm cells of P. aeruginosa strain PAO1 in a concentration dependent manner, this effect was less clear and varied considerably between different P. aeruginosa cystic fibrosis (CF) lung isolates. While a reduction in cell growth was observed after 8 h of CORM application, either no effect or even a slight increase in cell densities and the amount of biofilm was observed after 24 h. This variation could be partly explained by differences in bacterial virulence traits: while CF isolates showed attenuated in vivo virulence and growth compared to strain PAO1, they formed much more biofilm, which could have potentially protected them from the CORM. Even though no clear therapeutic benefits against a subset of isolates was observed in an in vivo wax moth acute infection model, EBOR-CORM-1 was more efficient at reducing the growth of CF isolate co-culture populations harboring intraspecific variation, in comparison with efficacy against more uniform single isolate culture populations. Together these results suggest that CORMs could be effective at controlling genetically diverse P. aeruginosa populations typical for natural chronic CF infections and that the potential benefits of some antibiotics might not be observed if tested only against clonal bacterial populations.