PDF(Pubmed)
Abstract：
Fungi and bacteria coexist in many polymicrobial communities, yet the molecular basis of their interactions remains poorly understood. Here, we show that the fungus Candida albicans sequesters essential magnesium ions from the bacterium Pseudomonas aeruginosa. To counteract fungal Mg2+ sequestration, P. aeruginosa expresses the Mg2+ transporter MgtA when Mg2+ levels are low. Thus, loss of MgtA specifically impairs P. aeruginosa in co-culture with C. albicans, but fitness can be restored by supplementing Mg2+. Using a panel of fungi and bacteria, we show that Mg2+ sequestration is a general mechanism of fungal antagonism against gram-negative bacteria. Mg2+ limitation enhances bacterial resistance to polymyxin antibiotics like colistin, which target gram-negative bacterial membranes. Indeed, experimental evolution reveals that P. aeruginosa evolves C. albicans-dependent colistin resistance via non-canonical means; antifungal treatment renders resistant bacteria colistin-sensitive. Our work suggests that fungal-bacterial competition could profoundly impact polymicrobial infection treatment with antibiotics of last resort.
摘要：
真菌和细菌共存于许多多微生物群落中，然而，它们相互作用的分子基础仍然知之甚少。这里,我们表明，真菌白色念珠菌从细菌铜绿假单胞菌中螯合必需的镁离子。为了对抗真菌Mg2+隔离，当Mg2+水平低时,铜绿假单胞菌表达Mg2+转运蛋白MgtA。因此，MgtA损失在与白色念珠菌共培养中特别损害铜绿假单胞菌，但是补充Mg2+可以恢复健康。使用一组真菌和细菌，我们表明Mg2+螯合是真菌拮抗革兰氏阴性菌的一般机制。Mg2+限制增强细菌对多粘菌素抗生素如粘菌素的耐药性，靶向革兰氏阴性细菌膜。的确,实验进化表明，铜绿假单胞菌通过非规范手段进化出依赖白色念珠菌的粘菌素抗性；抗真菌治疗使耐药细菌对粘菌素敏感。我们的工作表明，真菌-细菌竞争可能会极大地影响最后使用抗生素的多微生物感染治疗。
