Jung Yewon, Kim Jinshil, Ryu Sangryeol
Department of Food and Animal Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Department of Agricultural Biotechnology, Seoul National University, Seoul, 08826, Republic of Korea.
Arch Virol. 2025 Jul 3;170(8):172. doi: 10.1007/s00705-025-06358-7.
In combined treatments with antibiotics and bacteriophages (phages), antibiotics have the potential to influence phage infectivity, exhibiting effects that vary from synergistic to antagonistic. Here, we investigated the effects of various classes of antibiotics on Escherichia coli infection by phages that use different receptors, including vitamin B outer membrane transporter (BtuB), lipopolysaccharide (LPS), outer membrane protein A (OmpA), and nucleoside-specific porin (Tsx). Among the antibiotics tested, ampicillin did not affect phage infection, whereas colistin, chloramphenicol, and tetracycline inhibited phage infection irrespective of the phage receptor. In contrast, kanamycin inhibited infection of kanamycin-resistant E. coli by the BtuB-targeting phages, but not by the phages using LPS, OmpA, or Tsx. The receptor-specific antagonistic effect of kanamycin on BtuB-targeting phage infection was stronger than the effect observed with colistin, chloramphenicol, or tetracycline. When using a btuB-knockout mutant, we observed reduced kanamycin accumulation and increased kanamycin resistance compared to wild-type E. coli, suggesting that BtuB might be involved in kanamycin uptake. These results suggest that the antagonism between kanamycin and BtuB-targeting phage infection may be linked to the role of BtuB in facilitating kanamycin uptake. This study shows that the antimicrobial activity of phage-antibiotic combinations may be phage-receptor-specific, highlighting the need to consider phage receptors when selecting optimal combinations for effective phage therapy.
在抗生素与噬菌体联合治疗中，抗生素有可能影响噬菌体的感染性，其表现出的效果从协同到拮抗各不相同。在此，我们研究了各类抗生素对利用不同受体（包括维生素B外膜转运蛋白（BtuB）、脂多糖（LPS）、外膜蛋白A（OmpA）和核苷特异性孔蛋白（Tsx））的噬菌体感染大肠杆菌的影响。在所测试的抗生素中，氨苄西林不影响噬菌体感染，而黏菌素、氯霉素和四环素无论噬菌体受体如何均抑制噬菌体感染。相比之下，卡那霉素抑制靶向BtuB的噬菌体对卡那霉素抗性大肠杆菌的感染，但不抑制利用LPS、OmpA或Tsx的噬菌体的感染。卡那霉素对靶向BtuB的噬菌体感染的受体特异性拮抗作用强于黏菌素、氯霉素或四环素所观察到的作用。当使用btuB基因敲除突变体时，我们观察到与野生型大肠杆菌相比，卡那霉素积累减少且卡那霉素抗性增加，这表明BtuB可能参与卡那霉素的摄取。这些结果表明，卡那霉素与靶向BtuB的噬菌体感染之间的拮抗作用可能与BtuB在促进卡那霉素摄取中的作用有关。本研究表明，噬菌体 - 抗生素组合的抗菌活性可能具有噬菌体受体特异性，突出了在选择有效噬菌体治疗的最佳组合时考虑噬菌体受体的必要性。
