Macrophage killing of bacterial and fungal pathogens is not inhibited by intense intracellular accumulation of the lipoglycopeptide antibiotic oritavancin

巨噬细胞杀死细菌和真菌病原体的能力不会因脂糖肽类抗生素奥利万星在细胞内的大量积累而受到抑制

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作者:Beverlie Baquir, Sandrine Lemaire, Françoise Van Bambeke, Paul M Tulkens, Lin Lin, Brad Spellberg

Abstract

Intact phagocytic effector function is fundamental to host defense against microbial pathogens. Concern has been raised regarding the potential that accumulation of certain agents, including cationic amphiphilic antibiotics, within macrophages could cause a mixed-lipid storage disorder, resulting in macrophage dysfunction in recipients. The ability of 2 macrophage cell lines (HL-60; RAW 264.7) to kill archetypal Gram-positive (Staphylococcus aureus), Gram-negative (Acinetobacter baumannii), and fungal (Candida albicans) pathogens was tested following exposure of the macrophages to the lipoglycopeptide antibiotic oritavancin. Oritavancin did not affect killing of C. albicans but markedly enhanced killing of S. aureus by both macrophages. Oritavancin modestly reduced killing of A. baumannii by HL-60 cells but not by RAW 264.7 cells. Thus, macrophage killing of microbes remains intact despite substantial intracellular accumulation with a lipoglycopeptide antibiotic.

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