Vancomycin Derivative Inactivates Carbapenem-Resistant <i>Acinetobacter baumannii</i> and Induces Autophagy

Abstract

Vancomycin\nis a standard drug for the treatment of multidrug-resistant\nGram-positive bacterial infections. Albeit, development of resistance\n(VRE, VRSA) and its inefficacy against persistent infections is a\ndemerit. It is also intrinsically inactive against Gram-negative bacteria.\nHerein, we report a vancomycin derivative, VanQAmC₁₀, that\naddresses these challenges. VanQAmC₁₀ was rapidly bactericidal\nagainst carbapenem-resistant <i>A. baumannii</i> (6 log₁₀ CFU/mL reduction in 6 h), disrupted <i>A. baumannii</i> biofilms, and eradicated their stationary phase cells. In MRSA infected\nmacrophages, the compound reduced the bacterial burden by 1.3 log₁₀ CFU/mL while vancomycin exhibited a static effect. Further\ninvestigation indicated that the compound, unlike vancomycin, promoted\nthe intracellular degradative mechanism, autophagy, in mammalian cells,\nwhich may have contributed to its intracellular activity. The findings\nof the work provide new perspectives on the field of glycopeptide\nantibiotics.