Persister cell formation and biofilms of pathogens are extensively involved in the development of chronic infectious diseases. Eradicating persister cells is challenging, owing to their tolerance to conventional antibiotics, which cannot kill cells in a metabolically dormant state. A high frequency of persisters in biofilms makes inactivating biofilm cells more difficult, because the biofilm matrix inhibits antibiotic penetration. Fatty acids may be promising candidates as antipersister or antibiofilm agents, because some fatty acids exhibit antimicrobial effects. We previously reported that fatty acid ethyl esters effectively inhibit Escherichia coli persister formation by regulating an antitoxin. In this study, we screened a fatty acid library consisting of 65 different fatty acid molecules for altered persister formation. We found that undecanoic acid, lauric acid, and N-tridecanoic acid inhibited E. coli BW25113 persister cell formation by 25-, 58-, and 44-fold, respectively. Similarly, these fatty acids repressed persisters of enterohemorrhagic E. coli EDL933. These fatty acids were all medium-chain saturated forms. Furthermore, the fatty acids repressed EHEC biofilm formation (for example, by 8-fold for lauric acid) without having antimicrobial activity. This study demonstrates that medium-chain saturated fatty acids can serve as antipersister and antibiofilm agents that may be applied to treat bacterial infections.

中文翻译：

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十一烷酸、月桂酸和 N-十三烷酸可抑制大肠杆菌的持久性和生物膜的形成。


病原体的存留细胞形成和生物膜广泛参与慢性传染病的发展。根除持久细胞具有挑战性，因为它们对传统抗生素具有耐受性，而传统抗生素无法杀死处于代谢休眠状态的细胞。生物膜中高频率的持续存在使得生物膜细胞失活更加困难，因为生物膜基质抑制抗生素渗透。脂肪酸可能是作为抗持久剂或抗生物膜剂的有前途的候选者，因为一些脂肪酸表现出抗菌作用。我们之前报道过脂肪酸乙酯通过调节抗毒素有效抑制大肠杆菌持久菌的形成。在这项研究中，我们筛选了由 65 种不同脂肪酸分子组成的脂肪酸库，以改变持久细胞的形成。我们发现十一烷酸、月桂酸和 N-十三烷酸分别抑制大肠杆菌BW25113 持留细胞形成 25 倍、58 倍和 44 倍。同样，这些脂肪酸抑制了肠出血性大肠杆菌EDL933 的持续存在。这些脂肪酸都是中链饱和形式。此外，脂肪酸可抑制肠出血性大肠杆菌生物膜的形成（例如，月桂酸的抑制程度为 8 倍），但不具有抗菌活性。这项研究表明，中链饱和脂肪酸可以作为抗持久剂和抗生物膜剂，可用于治疗细菌感染。