With rising antibiotic resistance, alternative treatments for communicable diseases are increasingly relevant. One possible alternative for some types of infections is honey, used in wound care since before 2000 BCE and more recently in licensed, medical-grade products. However, it is unclear whether medical application of honey results in the evolution of bacterial honey resistance, and whether this has collateral effects on other bacterial traits such as antibiotic resistance. Here, we used single-step screening assays and serial transfer at increasing concentrations to isolate honey-resistant mutants of Escherichia coli. We only detected bacteria with consistently increased resistance to the honey they evolved in with two of the four tested honey products, and the observed increases were small (maximum two-fold increase in IC90). Genomic sequencing and experiments with single-gene knockouts showed a key mechanism by which bacteria increased their honey resistance was by mutating genes involved in detoxifying methylglyoxal, which contributes to the antibacterial activity of Leptospermum honeys. Crucially, we found no evidence that honey adaptation conferred cross-resistance or collateral sensitivity against nine antibiotics from six different classes. These results reveal constraints on bacterial adaptation to different types of honey, improving our ability to predict downstream consequences of wider honey application in medicine.

中文翻译：

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实验性细菌种群中蜂蜜抗性的演变取决于蜂蜜的类型，并且对抗生素敏感性没有重大副作用

随着抗生素耐药性的提高，传染病的替代治疗越来越重要。对于某些类型的感染，一种可能的替代方法是蜂蜜，该蜂蜜自公元前2000年开始用于伤口护理，最近用于许可的医疗级产品。但是，目前尚不清楚蜂蜜在医学上的应用是否会导致细菌对蜂蜜的抵抗力的演变，以及这是否会对其他细菌性状（如抗生素抵抗力）产生附带影响。在这里，我们使用单步筛选测定法和递增浓度的系列转移来分离大肠杆菌的蜂蜜抗性突变体。我们仅检测到了四种测试的蜂蜜产品中的两种产品对细菌进化产生的蜂蜜的抵抗力持续增加，并且观察到的细菌增加很小（IC90最多增加了两倍）。基因组测序和单基因敲除实验表明，细菌增加其蜂蜜抗性的关键机制是突变参与解毒甲基乙二醛的基因，这有助于精子草蜂蜜的抗菌活性。至关重要的是，我们没有发现证据表明蜂蜜适应性对六种不同类别的九种抗生素具有交叉耐药性或附带敏感性。这些结果揭示了细菌对不同类型蜂蜜的适应性限制，从而提高了我们预测在医学中广泛应用蜂蜜的下游后果的能力。它有助于瘦精子蜂蜜的抗菌活性。至关重要的是，我们没有发现证据表明蜂蜜适应性对六种不同类别的九种抗生素具有交叉耐药性或附带敏感性。这些结果揭示了细菌对不同类型蜂蜜的适应性限制，从而提高了我们预测在医学中广泛应用蜂蜜的下游后果的能力。它有助于瘦精子蜂蜜的抗菌活性。至关重要的是，我们没有发现证据表明蜂蜜适应性对六种不同类别的九种抗生素具有交叉耐药性或附带敏感性。这些结果揭示了细菌对不同类型蜂蜜的适应性限制，从而提高了我们预测在医学中广泛应用蜂蜜的下游后果的能力。