Azithromycin inhibits the intracellular persistence of Acinetobacter baumannii by inducing host cell autophagy in human bronchial epithelial cells.

Abstract

The invasion of host cells by bacteria, leading to intracellular infections, is a major cause of infection recurrence. Drug-resistant Acinetobacter baumannii (A. baumannii) is one of the most challenging public health issues worldwide, with very limited clinical treatment options available. A. baumannii has been found to be able to invade host cells and proliferate within them in recent studies. In addition to the direct antimicrobial effect of antibiotics, the activation of host autophagic flux also plays an important role in eliminating intracellular pathogens. Herein, this study aimes to evaluate the clearance effect of antibiotics on intracellular A. baumannii both in vivo and in vitro, and explore the relationship between this effect and autophagy. The results showed that intracellular pathogens resulted in a significant increase in the minimum bactericidal concentration, while azithromycin can significantly eliminate intracellular A. baumannii in vitro and in vivo. Notably, 60 μg/mL azithromycin demonstrated intracellular clearance against multidrug-resistant A. baumannii and markedly induced autophagosomes in BEAS-2B cells with a mild stimulation of autophagosomes degradation. These findings indicated that azithromycin can significantly clear intracellular A. baumannii and its ability to clear intracellular A. baumannii may be related to the stimulation of autophagosome formation and the induction of host autophagy, which has important implications for the clinical treatment of A. baumannii infections, especially when intracellular infections are present.