Department of Civil and Environmental Engineering, Rice University, Houston, Texas, USA.
Appl Environ Microbiol. 2021 Jul 13;87(15):e0046821. doi: 10.1128/AEM.00468-21.
The common cooccurrence of antibiotics and phages in both natural and engineered environments underscores the need to understand their interactions and implications for bacterial control and antibiotic resistance propagation. Here, aminoglycoside antibiotics that inhibit protein synthesis (e.g., kanamycin and neomycin) impeded the replication of coliphage T3 and phage BSP, reducing their infection efficiency and mitigating their hindrance of bacterial growth, biofilm formation, and tolerance to antibiotics. For example, treatment with phage T3 reduced subsequent biofilm formation by Escherichia coli liquid cultures to 53% ± 5% of that of the no-phage control, but a smaller reduction of biofilm formation (89% ± 10%) was observed for combined exposure to phage T3 and kanamycin. Despite sharing a similar mode of action with aminoglycosides (i.e., inhibiting protein synthesis) and antagonizing phage replication, albeit to a lesser degree, tetracyclines did not inhibit bacterial control by phages. Phage T3 combined with tetracycline showed higher suppression of biofilm formation than when combined with aminoglycosides (25% ± 6% of the no-phage control). The addition of phage T3 to E. coli suspensions with tetracycline also suppressed the development of tolerance to tetracycline. However, this suppression of antibiotic tolerance development disappeared when tetracycline was replaced with 3 mg/liter kanamycin, corroborating the greater antagonism with aminoglycosides. Overall, this study highlights this overlooked antagonistic effect on phage proliferation, which may attenuate phage suppression of bacterial growth, biofilm formation, antibiotic tolerance, and maintenance of antibiotic resistance genes. The coexistence of residual antibiotics and phages is common in many environments, which underscores the need to understand their interactive effects on bacteria and the implications for antibiotic resistance propagation. Here, aminoglycosides acting as bacterial protein synthesis inhibitors impeded the replication of various phages. This alleviated the suppressive effects of phages against bacterial growth and biofilm formation and diminished bacterial fitness costs that suppress the emergence of tolerance to antibiotics. We show that changes in bacteria caused by environmentally relevant concentrations of sublethal antibiotics can affect phage-host dynamics that are commonly overlooked but can result in unexpected environmental consequences.
在自然和工程环境中，抗生素和噬菌体的共同存在突出表明需要了解它们的相互作用及其对细菌控制和抗生素耐药性传播的影响。在这里，抑制蛋白质合成的氨基糖苷类抗生素（例如卡那霉素和新霉素）阻碍了噬菌体 T3 和噬菌体 BSP 的复制，从而降低了它们的感染效率，并减轻了它们对细菌生长、生物膜形成和抗生素耐药性的阻碍。例如，噬菌体 T3 的处理将大肠杆菌液体培养物的随后生物膜形成降低至无噬菌体对照的 53%±5%，但当同时暴露于噬菌体 T3 和卡那霉素时，生物膜形成的减少幅度较小（89%±10%）。尽管氨基糖苷类药物（即抑制蛋白质合成）和噬菌体复制具有相似的作用模式，并且在较小程度上拮抗噬菌体复制，但四环素类药物并未抑制噬菌体对细菌的控制。噬菌体 T3 与四环素联合使用比与氨基糖苷类药物联合使用时更能抑制生物膜形成（无噬菌体对照的 25%±6%）。噬菌体 T3 与四环素联合使用还抑制了大肠杆菌悬浮液对四环素的耐药性发展。然而，当用 3mg/L 的卡那霉素代替四环素时，这种对抗生素耐药性发展的抑制作用消失了，这与氨基糖苷类药物的拮抗作用更强是一致的。总的来说，这项研究强调了这种对噬菌体增殖的被忽视的拮抗作用，这可能会减弱噬菌体对细菌生长、生物膜形成、抗生素耐药性和抗生素耐药基因维持的抑制作用。在许多环境中，残留抗生素和噬菌体共存是很常见的，这突出表明需要了解它们对细菌的相互作用及其对抗生素耐药性传播的影响。在这里，作为细菌蛋白质合成抑制剂的氨基糖苷类药物阻碍了各种噬菌体的复制。这减轻了噬菌体对细菌生长和生物膜形成的抑制作用，并降低了抑制抗生素耐药性出现的细菌适应性成本。我们表明，亚致死浓度的环境相关抗生素引起的细菌变化会影响噬菌体-宿主动态，这通常被忽视，但会导致意想不到的环境后果。
