Drug-mediated metabolic tipping between antibiotic resistant states in a mixed-species community.
Drug-mediated metabolic tipping between antibiotic resistant states in a mixed-species community.
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DOI：
10.1038/s41559-018-0582-7
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发表时间：
2018-08
影响因子：
16.8
通讯作者：
Gudelj I
中科院分区：
文献类型：
--
作者：
Beardmore RE;Cook E;Nilsson S;Smith AR;Tillmann A;Esquivel BD;Haynes K;Gow NAR;Brown AJP;White TC;Gudelj I
微生物很少孤立存在，相反，它们形成复杂的多物种群落，在我们的身体和插入的医疗设备中定居。然而，抗微生物剂的功效在临床实验室中仅使用微生物单一培养物来测量。在这里，为了确定多物种相互作用如何介导抗生素治疗期间的耐药性选择，特别是在停药后，我们研究了由两种微生物病原体组成的实验室群落。单物种剂量反应不能很好地预测治疗期间的群落动态，因此，为了更好地了解这些动态，我们引入了剂量反应马赛克的概念，这是一张多维地图，表明物种丰度如何受到非生物变化的影响。条件。我们研究了两个物种社区的剂量-反应镶嵌与“基因×基因×环境×环境”的生态相互作用，其中光滑念珠菌，这是抗真菌药物氟康唑，竞争生存与白色念珠菌，这是敏感的氟康唑。马赛克由几个区域组成，这些区域描绘了每个物种占主导地位的非生物条件。区域由分叉点和临界点的位置分开，这些位置确定了什么样的环境变化会引发任何一个物种的消失。对实验室群落的观察证实了这一理论，表明抗生素浓度和营养物质供应的变化可以推动种群超越临界点，从而使群落组成从药物敏感物种向耐药物种发生不可逆转的转变。这有一个重要的后果：即使抗生素被撤回，耐药物种的频率也会增加，因为在治疗过程中不知不觉地超过了临界点。
Microbes rarely exist in isolation, rather, they form intricate multi-species communities that colonize our bodies and inserted medical devices. However, the efficacy of antimicrobials is measured in clinical laboratories exclusively using microbial monocultures. Here, to determine how multi-species interactions mediate selection for resistance during antibiotic treatment, particularly following drug withdrawal, we study a laboratory community consisting of two microbial pathogens. Single-species dose responses are a poor predictor of community dynamics during treatment so, to better understand those dynamics, we introduce the concept of a dose-response mosaic, a multi-dimensional map that indicates how species’ abundance is affected by changes in abiotic conditions. We study the dose-response mosaic of a two-species community with a ‘Gene × Gene × Environment × Environment’ ecological interaction whereby Candida glabrata, which is resistant to the antifungal drug fluconazole, competes for survival with Candida albicans, which is susceptible to fluconazole. The mosaic comprises several zones that delineate abiotic conditions where each species dominates. Zones are separated by loci of bifurcations and tipping points that identify what environmental changes can trigger the loss of either species. Observations of the laboratory communities corroborated theory, showing that changes in both antibiotic concentration and nutrient availability can push populations beyond tipping points, thus creating irreversible shifts in community composition from drug-sensitive to drug-resistant species. This has an important consequence: resistant species can increase in frequency even if an antibiotic is withdrawn because, unwittingly, a tipping point was passed during treatment.
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影响因子：
8.8
作者：
Carpenter, SR;Brock, WA
通讯作者：
Brock, WA
DOI：
10.1073/pnas.0802430105
发表时间：
2008-09-23
影响因子：
11.1
作者：
Dakos, Vasilis;Scheffer, Marten;Held, Hermann
通讯作者：
Held, Hermann
影响因子：
3
作者：
Basson, NJ
通讯作者：
Basson, NJ
DOI：
10.1038/nrmicro2259
发表时间：
2010-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1164/ajrccm.162.3.9905050
发表时间：
2000-09-01
影响因子：
24.7
作者：
Gruson, D;Hilbert, G;Cardinaud, JP
通讯作者：
Cardinaud, JP