Individual bacteria in structured environments rely on phenotypic resistance to phage.
Individual bacteria in structured environments rely on phenotypic resistance to phage.
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DOI：
10.1371/journal.pbio.3001406
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发表时间：
2021-10
期刊：
影响因子：
9.8
通讯作者：
Pagliara S
中科院分区：
文献类型：
--
作者：
Attrill EL;Claydon R;Łapińska U;Recker M;Meaden S;Brown AT;Westra ER;Harding SV;Pagliara S
噬菌体代表了克服当前抗生素耐药性危机的一种途径，但对抗生素的遗传耐药性的进化仍然是一个令人担忧的问题。在体外，细菌进化出遗传抗性，防止噬菌体吸附或降解噬菌体DNA。在自然环境中，进化的抗性较低，可能是因为生物膜、小菌落或壁种群内的空间异质性有利于表型存活至裂解性。然而，遗传敏感细菌的持续存在也可能是由于自然环境中噬菌体扩增效率较低，细菌可以隐藏的避难所的存在以及耐药基因型的传播减少。在这里，我们通过跟踪单个细胞的存活来监测在短暂避难所中隔离的单个寄生细菌与噬菌体之间的相互作用。我们发现，在这些短暂的空间避难所，由于减少表达的噬菌体受体的表型抗性是细菌存活的关键决定因素。这种生存策略与在混合良好的环境中没有短暂避难所的情况下出现的遗传抗性形成对比。通过一个数学建模框架来跟踪细菌对细菌的反应所产生的预测表明，空间避难所的存在导致了根本不同的种群动态，为了预测和操纵自然结构环境中细菌-噬菌体相互作用的进化和生态动态，应该考虑这些种群动态。噬菌体代表了克服当前抗生素耐药性危机的有希望的途径，但噬菌体耐药性的演变仍然是一个问题。这项研究表明，在空间避难所的存在下，对噬菌体的遗传抗性比通常假设的问题要小，但遗传易感细菌的持续存在表明，从结构化环境中根除细菌病原体可能需要联合噬菌体抗生素疗法。
Bacteriophages represent an avenue to overcome the current antibiotic resistance crisis, but evolution of genetic resistance to phages remains a concern. In vitro, bacteria evolve genetic resistance, preventing phage adsorption or degrading phage DNA. In natural environments, evolved resistance is lower possibly because the spatial heterogeneity within biofilms, microcolonies, or wall populations favours phenotypic survival to lytic phages. However, it is also possible that the persistence of genetically sensitive bacteria is due to less efficient phage amplification in natural environments, the existence of refuges where bacteria can hide, and a reduced spread of resistant genotypes. Here, we monitor the interactions between individual planktonic bacteria in isolation in ephemeral refuges and bacteriophage by tracking the survival of individual cells. We find that in these transient spatial refuges, phenotypic resistance due to reduced expression of the phage receptor is a key determinant of bacterial survival. This survival strategy is in contrast with the emergence of genetic resistance in the absence of ephemeral refuges in well-mixed environments. Predictions generated via a mathematical modelling framework to track bacterial response to phages reveal that the presence of spatial refuges leads to fundamentally different population dynamics that should be considered in order to predict and manipulate the evolutionary and ecological dynamics of bacteria–phage interactions in naturally structured environments. Bacteriophages represent a promising avenue to overcome the current antibiotic resistance crisis, but evolution of phage resistance remains a concern. This study shows that in the presence of spatial refuges, genetic resistance to phage is less of a problem than commonly assumed, but the persistence of genetically susceptible bacteria suggests that eradicating bacterial pathogens from structured environments may require combined phage-antibiotic therapies.
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DOI：
10.1098/rspb.2003.2556
发表时间：
2004-01-07
影响因子：
4.7
作者：
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通讯作者：
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影响因子：
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影响因子：
1.7
作者：
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DOI：
10.1073/pnas.1708954115
发表时间：
2018-01-09
影响因子：
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通讯作者：
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