Phage cocktail strategies for the suppression of a pathogen in a cross-feeding coculture.,Microbial Biotechnology

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Phage cocktail strategies for the suppression of a pathogen in a cross-feeding coculture.
Microbial Biotechnology ( IF 4.8 ) Pub Date : 2020-08-19 , DOI: 10.1111/1751-7915.13650
Lisa Fazzino _{1,

2} , Jeremy Anisman _{3,

4} , Jeremy M Chacón _{2,

5} , William R Harcombe _{2,

5}

Affiliation

Cocktail combinations of bacteria‐infecting viruses (bacteriophages) can suppress pathogenic bacterial growth. However, predicting how phage cocktails influence microbial communities with complex ecological interactions, specifically cross‐feeding interactions in which bacteria exchange nutrients, remains challenging. Here, we used experiments and mathematical simulations to determine how to best suppress a model pathogen, E. coli, when obligately cross‐feeding with S. enterica. We tested whether the duration of pathogen suppression caused by a two‐lytic phage cocktail was maximized when both phages targeted E. coli, or when one phage targeted E. coli and the other its cross‐feeding partner, S. enterica. Experimentally, we observed that cocktails targeting both cross‐feeders suppressed E. coli growth longer than cocktails targeting only E. coli. Two non‐mutually exclusive mechanisms could explain these results: (i) we found that treatment with two E. coli phage led to the evolution of a mucoid phenotype that provided cross‐resistance against both phages, and (ii) S. enterica set the growth rate of the coculture, and therefore, targeting S. enterica had a stronger effect on pathogen suppression. Simulations suggested that cross‐resistance and the relative growth rates of cross‐feeders modulated the duration of E. coli suppression. More broadly, we describe a novel bacteriophage cocktail strategy for pathogens that cross‐feed.

中文翻译：

在交叉饲养共培养物中抑制病原体的噬菌体鸡尾酒策略。

细菌感染病毒（噬菌体）的混合物可以抑制致病细菌的生长。然而，预测噬菌体混合物如何影响具有复杂生态相互作用的微生物群落，特别是细菌交换营养物质的交叉喂养相互作用，仍然具有挑战性。在这里，我们使用实验和数学模拟来确定当与肠沙门氏菌强制交叉喂养时如何最好地抑制模型病原体大肠杆菌。我们测试了当两种噬菌体都针对大肠杆菌时，或者当一种噬菌体针对大肠杆菌而另一种噬菌体针对其交叉喂养伙伴肠沙门氏菌时，双裂解噬菌体混合物引起的病原体抑制持续时间是否最大化。通过实验，我们观察到针对两个交叉饲养者的混合物比仅针对大肠杆菌的混合物抑制大肠杆菌生长的时间更长。两种非相互排斥的机制可以解释这些结果：（i）我们发现用两种大肠杆菌噬菌体处理导致了粘液表型的进化，该表型提供了对两种噬菌体的交叉抗性，并且（ii）肠沙门氏菌设定了共培养物的生长速度，因此，针对肠沙门氏菌对病原体抑制具有更强的效果。模拟表明，交叉耐药性和交叉饲养者的相对生长率调节了大肠杆菌抑制的持续时间。更广泛地说，我们描述了一种针对交叉喂养的病原体的新型噬菌体混合物策略。

更新日期：2020-10-05

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