<i>Mycobacterium smegmatis</i> Resists the Bactericidal Activity of Hypochlorous Acid Produced in Neutrophil Phagosomes

Abstract Neutrophils are often the major leukocyte at sites of mycobacterial infection, yet little is known about their ability to kill mycobacteria. In this study we have investigated whether potent antibacterial oxidant hypochlorous acid (HOCl) contributes killing Mycobacterium smegmatis when bacterium phagocytosed by human neutrophils. We found that M. were ingested neutrophils into intracellular phagosomes but killed slowly. measured a t1/2 30 min for survival inside neutrophils, which 5 times longer than reported Staphylococcus aureus and 15 Escherichia coli. Live-cell imaging indicated generated HOCl in containing smegmatis; however, inhibition production did not alter rate bacterial killing. Also, doses likely be produced failed isolated bacteria. Lethal reagent caused oxidation mycothiol, main low-m.w. thiol bacterium. contrast, maintained original level reduced mycothiol. Collectively, these findings suggest can cope with neutrophil phagosomes. A mycothiol-deficient mutant was same as wild-type bacteria, indicating mycothiol itself driver resistance. Understanding how avoids phagosomal could provide new opportunities sensitize pathogenic mycobacteria destruction innate immune system.