Antibiotics such as β-lactams and aminoglycosides are often subtherapeutic to intracellular infections due to their high hydrophilicity, resulting in low effectiveness against intracellular pathogens and the emergence of antibiotic resistance. Here we reported that an endogenous aminoglycan, hyaluronic acid could be an effective carbohydrate carrier of the aminoglycoside antibiotic, streptomycin against intracellular pathogens. This conjugation could enhance phagocytic activity, and facilitated the entry of streptomycin into host cells via a CD44-mediated pathway. It appeared that this conjugate could clear intracellular bacteria in phagocytic or nonphagocytic cells in a short-term therapy (4 h) at a lower effective dose. In addition, this conjugate was more efficient in reducing bacteria burden in an in vivo acute infection model than streptomycin did. Interestingly, subcutaneous injection of this conjugate at an excess amount had undetectable side effects such as nephrotoxicity. These results suggested that hyaluronic acid might be an efficient Trojan horse for the delivery of hydrophilic antibiotics to deal with intracellular infections.

中文翻译：

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透明质酸结合促进链霉素清除细胞内细菌感染，且肾毒性可忽略不计

诸如β-内酰胺和氨基糖苷类的抗生素由于它们的高亲水性，经常对细胞内感染亚治疗，从而导致针对细胞内病原体的效力低下和出现抗生素抗性。在这里，我们报道了内源性氨基聚糖，透明质酸可能是氨基糖苷类抗生素链霉素对细胞内病原体的有效碳水化合物载体。这种结合可以增强吞噬活性，并促进链霉素通过CD44介导的途径进入宿主细胞。似乎这种结合物可以在短期治疗（4 h）中以较低的有效剂量清除吞噬细胞或非吞噬细胞中的细胞内细菌。此外，与链霉素相比，这种结合物在体内急性感染模型中在减少细菌负担方面更有效。有趣的是，过量的这种缀合物的皮下注射具有不可检测的副作用，例如肾毒性。这些结果表明，透明质酸可能是一种有效的特洛伊木马，用于递送亲水性抗生素以应对细胞内感染。