Data from: Effects of prior exposure to antibiotics on bacterial adaptation to phages

Understanding adaptation to complex environments requires information about how exposure to one selection pressure affects adaptation to others. For bacteria, antibiotics and viral parasites (phages) are two of the most common selection pressures and are both relevant for treatment of bacterial infections: increasing antibiotic resistance is generating significant interest in using phages in addition or as an alternative to antibiotics. However, we lack knowledge of how exposure to antibiotics affects bacterial responses to phages. Specifically, it is unclear how the negative effects of antibiotics on bacterial population growth combine with any possible mutagenic effects or physiological responses to influence adaptation to other stressors such as phages, and how this net effect varies with antibiotic concentration. Here, we experimentally addressed the effect of pre-exposure to a wide range of antibiotic concentrations on bacterial responses to phages. Across 10 antibiotics, we found a strong association between their effects on bacterial population size and subsequent population growth in the presence of phages (which in these conditions indicates phage-resistance evolution). We detected some evidence of mutagenesis among populations treated with fluoroquinolones, quinolones and β-lactams at sub-lethal doses, but these effects were small and not consistent across phage treatments. These results show that, although stressors such as antibiotics can boost adaptation to other stressors at low concentrations, these effects are weak compared to the effect of reduced population growth at inhibitory concentrations, which in our experiments strongly reduced the likelihood of subsequent phage-resistance evolution.

解析生物对复杂环境的适应性机制，需明确单一选择压力的暴露如何影响生物对其他选择压力的适应性。对于细菌而言，抗生素与病毒寄生物（噬菌体，phage）是两类最为常见的选择压力，二者均与细菌感染的治疗密切相关：日益严重的抗生素耐药性问题使得学界愈发关注将噬菌体作为抗生素的补充或替代疗法。然而，目前我们仍不清楚抗生素暴露如何影响细菌对噬菌体的应答反应。具体而言，我们尚不明确：抗生素对细菌种群生长的负面影响，与可能存在的诱变效应或生理应答，二者如何共同作用，影响细菌对噬菌体这类其他胁迫因子的适应性；同时也不清楚该净效应如何随抗生素浓度变化而改变。本研究通过实验探究了不同浓度抗生素预暴露对细菌噬菌体应答反应的影响。针对10种抗生素的实验结果显示，抗生素对细菌种群规模的影响，与噬菌体存在条件下细菌后续的种群生长之间存在显著关联（该关联在本实验条件下可指示噬菌体抗性的进化）。我们在经亚致死剂量氟喹诺酮类、喹诺酮类及β-内酰胺类抗生素处理的细菌种群中，检测到了一定的诱变证据，但此类效应强度较弱，且在不同噬菌体处理组间并不一致。本研究结果表明：尽管像抗生素这类胁迫因子在低浓度下可增强细菌对其他胁迫因子的适应性，但与抑制性浓度下种群生长受抑制所带来的效应相比，此类增强作用十分微弱——在本实验中，种群生长受抑制会显著降低后续噬菌体抗性进化的可能性。