Data from: Bacterial competition and quorum-sensing signalling shapes the eco-evolutionary outcomes of model in vitro phage therapy

The rapid rise of antibiotic resistance has renewed interest in phage therapy – the use of bacteria-specific viruses (phages) to treat bacterial infections. Even though phages are often pathogen-specific, little is known about the efficiency and eco-evolutionary outcomes of phage therapy in polymicrobial infections. We studied this experimentally by exposing both quorum sensing (QS) signalling PAO1 and QS-deficient lasR Pseudomonas aeruginosa genotypes (differing in their ability to signal intra-specifically) to lytic PT7 phage in the presence and absence of two bacterial competitors: Staphylococcus aureus and Stenotrophomonas maltophilia – two bacteria commonly associated with P. aeruginosa in polymicrobial cystic fibrosis lung infections. Both the P. aeruginosa genotype and the presence of competitors had profound effects on bacteria and phage densities and bacterial resistance evolution. In general, competition reduced the P. aeruginosa frequencies leading to a lower rate of resistance evolution. This effect was clearer with QS-signalling PAO1 strain due to lower bacteria and phage densities and relatively larger pleiotropic growth cost imposed by both phage and competitors. Unexpectedly, phage selection decreased the total bacterial densities in the QS-deficient lasR pathogen communities, while an increase was observed in the QS-signalling PAO1 pathogen communities. Together these results suggest that bacterial competition can shape the eco-evolutionary outcomes of phage therapy.

抗生素耐药性的快速兴起重新唤起了学界对噬菌体疗法（phage therapy）的关注——该疗法指利用以细菌为特异性宿主的病毒（噬菌体，phage）治疗细菌感染。尽管噬菌体通常具有病原体特异性，但目前人们对多微生物感染环境下噬菌体疗法的疗效及其生态-进化结局知之甚少。本研究通过实验手段开展相关探究：将具备群体感应（quorum sensing, QS）信号通路的PAO1菌株，与群体感应缺陷型lasR铜绿假单胞菌（Pseudomonas aeruginosa）基因型菌株（二者种内信号传导能力存在差异），分别置于添加或不添加两种细菌竞争者——金黄色葡萄球菌（Staphylococcus aureus）与嗜麦芽窄食单胞菌（Stenotrophomonas maltophilia）——的环境中，使其接触裂解性PT7噬菌体（PT7 phage），上述两种细菌常与铜绿假单胞菌共生于多微生物性囊性纤维化肺部感染病灶内。铜绿假单胞菌的基因型与竞争者的存在与否，均对细菌与噬菌体的密度以及细菌的耐药性进化产生了显著影响。总体而言，竞争者的存在降低了铜绿假单胞菌的相对丰度，进而导致耐药性进化速率下降。这一效应在具备QS信号通路的PAO1菌株中更为显著，原因在于该菌株的细菌与噬菌体密度更低，且噬菌体与竞争者共同施加的多效性生长成本相对更高。出乎意料的是，噬菌体选择压力使群体感应缺陷型lasR病原体群落的总细菌密度下降，而在具备QS信号通路的PAO1病原体群落中则观察到总细菌密度上升。综合上述结果可知，细菌竞争可塑造噬菌体疗法的生态-进化结局。