Marton Huba L, Sagona Antonia P, Kilbride Peter, Gibson Matthew I
Department of Chemistry, University of Warwick Coventry CV4 7AL UK
School of Life Sciences, University of Warwick Coventry CV4 7AL UK
RSC Appl Polym. 2024 Aug 23;2(6):1082-1090. doi: 10.1039/d4lp00202d. eCollection 2024 Nov 14.
Bacteriophages are promising as therapeutics and biotechnological tools, but they also present a problem for routine and commercial bacterial cultures, where contamination must be avoided. Poly(carboxylic acids) have been reported to inhibit phages' ability to infect their bacterial hosts and hence offer an exciting route to discover additives to prevent infection. Their mechanism and limitations have not been explored. Here, we report the role of pH in inactivating phages to determine if the polymers are unique or simply acidic. It is shown that lower pH (=3) triggered by either acidic polymers or similar changes in pH using HCl lead to inhibition. There is no inhibitory activity at higher pHs (in growth media). This was shown across a panel of phages and different molecular weights of commercial and controlled-radical polymerization-derived poly(acrylic acid)s. It is shown that poly(acrylic acid) leads to reversible deactivation of phage, but when the pH is adjusted using HCl alone the phage is irreversibly deactivated. Further experiments using metal binders ruled out ion depletion as the mode of action. These results show that polymeric phage inhibitors may work by unique mechanisms of action and that pH alone cannot explain the observed effects whilst also placing constraints on the practical utility of poly(acrylic acid).
噬菌体有望成为治疗手段和生物技术工具，但它们也给常规和商业细菌培养带来了问题，因为必须避免污染。据报道，聚羧酸能抑制噬菌体感染其细菌宿主的能力，因此为发现预防感染的添加剂提供了一条令人兴奋的途径。其作用机制和局限性尚未得到探索。在这里，我们报告了pH值在使噬菌体失活中的作用，以确定这些聚合物是具有独特性还是仅仅呈酸性。结果表明，由酸性聚合物引发的较低pH值（=3）或使用HCl使pH值发生类似变化都会导致抑制作用。在较高pH值（在生长培养基中）时没有抑制活性。这在一组噬菌体以及不同分子量的商业和可控自由基聚合衍生的聚丙烯酸中都得到了证实。结果表明，聚丙烯酸会导致噬菌体可逆失活，但仅使用HCl调节pH值时，噬菌体会不可逆失活。使用金属结合剂的进一步实验排除了离子耗竭作为作用方式。这些结果表明，聚合物噬菌体抑制剂可能通过独特的作用机制起作用，仅pH值不能解释观察到的效果，同时也对聚丙烯酸的实际应用施加了限制。
