Artificial sweeteners inhibit multidrug-resistant pathogen growth and potentiate antibiotic activity.
Artificial sweeteners inhibit multidrug-resistant pathogen growth and potentiate antibiotic activity.
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DOI：
10.15252/emmm.202216397
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发表时间：
2023-01-11
影响因子：
11.1
通讯作者：
McCarthy, Ronan R.
中科院分区：
文献类型：
--
作者：
de Dios, Ruben;Proctor, Chris R.;Maslova, Evgenia;Dzalbe, Sindija;Rudolph, Christian J.;McCarthy, Ronan R.
抗生素耐药性是我们这个时代最紧迫的问题之一。人类饮食中含有丰富的化合物，可以改变细菌肠道群落和毒力相关行为，这表明食品添加剂可能是发现新型抗毒力化合物的利基。在这里，我们确定了三种人工甜味剂，糖精，甜蜜素和乙酰磺胺酸钾（ace-K），对优先病原体具有主要的生长抑制作用。我们进一步验证了ace-K对多重耐药鲍曼不动杆菌的影响，证明它可以使毒力行为失效，如生物膜形成、运动性和获得外源抗生素耐药基因的能力。进一步的分析表明，生长抑制的机制是通过隆突介导的细胞溶解，并且可以通过阳离子补充来拯救细胞。抗生素敏感性试验表明，在亚致死浓度下，ace-K可以使A重新敏感。鲍曼不动杆菌感染者最后使用抗生素，包括碳青霉烯类。使用一种新的离体猪皮肤伤口模型，我们表明ace-K的抗微生物活性在伤口微环境中得以维持。我们的研究结果证明了人工甜味剂对病原体行为的影响，并揭示了它们的治疗潜力。人工甜味剂可以抑制多重耐药病原体的生长，破坏与毒力相关的行为，并增强抗生素活性。在伤口模型中，甜味剂Acesulfame K显示出作为局部伤口治疗的潜力。
Antimicrobial resistance is one of the most pressing concerns of our time. The human diet is rich with compounds that alter bacterial gut communities and virulence‐associated behaviours, suggesting food additives may be a niche for the discovery of novel anti‐virulence compounds. Here, we identify three artificial sweeteners, saccharin, cyclamate and acesulfame‐K (ace‐K), that have a major growth inhibitory effect on priority pathogens. We further characterise the impact of ace‐K on multidrug‐resistant Acinetobacter baumannii, demonstrating that it can disable virulence behaviours such as biofilm formation, motility and the ability to acquire exogenous antibiotic‐resistant genes. Further analysis revealed the mechanism of growth inhibition is through bulge‐mediated cell lysis and that cells can be rescued by cation supplementation. Antibiotic sensitivity assays demonstrated that at sub‐lethal concentrations, ace‐K can resensitise A. baumannii to last resort antibiotics, including carbapenems. Using a novel ex vivo porcine skin wound model, we show that ace‐K antimicrobial activity is maintained in the wound microenvironment. Our findings demonstrate the influence of artificial sweeteners on pathogen behaviour and uncover their therapeutic potential. Artificial sweeteners can inhibit the growth of multidrug resistant pathogens, disrupt virulence associated behaviours and potentiate antibiotic activity. In wound models the sweetener, Acesulfame K, shows potential as a topical wound treatment.
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影响因子：
4.5
作者：
Andrade FF;Silva D;Rodrigues A;Pina-Vaz C
通讯作者：
Pina-Vaz C
影响因子：
48
作者：
Choi, KH;Gaynor, JB;Schweizer, HP
通讯作者：
Schweizer, HP
影响因子：
4.3
作者：
Chappell, G. A.;Wikoff, D. S.;Borghoff, S. J.
通讯作者：
Borghoff, S. J.
影响因子：
4.2
作者：
Cai B;Echols R;Magee G;Arjona Ferreira JC;Morgan G;Ariyasu M;Sawada T;Nagata TD
通讯作者：
Nagata TD
影响因子：
2.9
作者：
Guest JF;Fuller GW;Vowden P
通讯作者：
Vowden P