Davis Carly M, McCutcheon Jaclyn G, Dennis Jonathan J
Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Microorganisms. 2021 Jan 12;9(1):152. doi: 10.3390/microorganisms9010152.
is a pernicious bacterial pathogen that is difficult to treat because of high levels of antibiotic resistance. A promising alternative treatment option for such bacteria is the application of bacteriophages; the correct combination of phages plus antibiotics can produce synergistic inhibitory effects. In this study, we describe morphological changes induced by sub-MIC levels of the antibiotic aztreonam lysine (AzLys) on PA01, which may in part explain the observed phage-antibiotic synergy (PAS). One-step growth curves for phage E79 showed increased adsorption rates, decreased infection latency, accelerated time to lysis and a minor reduction in burst size. Phage E79 plus AzLys PAS was also able to significantly reduce biofilm growth over 3-fold as compared to phage treatment alone. Sub-inhibitory AzLys-induced filamentation of cells resulted in loss of twitching motility and a reduction in swimming motility, likely due to a reduction in the number of polar Type IV pili and flagella, respectively, on the filamented cell surfaces. Phage phiKZ, which uses Type IV pili as a receptor, did not exhibit increased activity with AzLys at lower sub-inhibitory levels, but still produced phage-antibiotic synergistic killing with sub-inhibitory AzLys. A one-step growth curve indicates that phiKZ in the presence of AzLys also exhibits a decreased infection latency and moderately undergoes accelerated time to lysis. In contrast to prior PAS studies demonstrating that phages undergo delayed time to lysis with cell filamentation, these PAS results show that phages undergo accelerated time to lysis, which therefore suggests that PAS is dependent upon multiple factors, including the type of phages and antibiotics used, and the bacterial host being tested.
是一种有害的细菌病原体，由于其高水平的抗生素耐药性而难以治疗。对于此类细菌，一种有前景的替代治疗选择是应用噬菌体；噬菌体与抗生素的正确组合可产生协同抑制作用。在本研究中，我们描述了亚抑菌水平的抗生素氨曲南赖氨酸（AzLys）对PA01诱导的形态变化，这可能部分解释了观察到的噬菌体 - 抗生素协同作用（PAS）。噬菌体E79的一步生长曲线显示吸附率增加、感染潜伏期缩短、裂解时间加速且爆发量略有减少。与单独的噬菌体处理相比，噬菌体E79加AzLys的PAS还能够显著减少生物膜生长超过3倍。亚抑菌浓度的AzLys诱导的细胞丝化导致颤动运动丧失和游动运动减少，可能分别是由于丝化细胞表面上极性IV型菌毛和鞭毛数量的减少。以IV型菌毛作为受体的噬菌体phiKZ在较低的亚抑菌水平下与AzLys一起未表现出活性增加，但仍与亚抑菌浓度的AzLys产生噬菌体 - 抗生素协同杀伤作用。一步生长曲线表明，在存在AzLys的情况下phiKZ也表现出感染潜伏期缩短并适度加速裂解时间。与先前的PAS研究表明噬菌体随着细胞丝化裂解时间延迟相反，这些PAS结果表明噬菌体裂解时间加速，因此表明PAS取决于多种因素，包括所用噬菌体和抗生素的类型以及所测试的细菌宿主。
