N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Amaral, Eduardo; Conceição, Elisabete; Costa, Diego; Rocha, Michael; Marinho, Jamocyr; Cordeiro-Santos, Marcelo; D'Império-Lima, Maria; Barbosa, Theolis; Sher, Alan; Andrade, Bruno
• Is Part Of: BMC microbiology. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Tuberculosis -- N-acetyl cysteine -- Antimicrobial activity -- Therapy; Microbiology -- Periodicals; 579.05
• DOI: 10.1186/s12866-016-0872-7
• Languages: English
• ISSNs: 1471-2180

Abstract

Abstract Background Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria. Methods Oxidative stress status in plasma was compared between pulmonary TB (PTB) patients and those with latentM. tuberculosis infection (LTBI) or healthy uninfected individuals. Lipid peroxidation, DNA oxidation and cell death, as well as accumulation of reactive oxygen species (ROS) were measured in cultures of primary human monocyte-derived macrophages infected withM. tuberculosis and treated or not with NAC.M. tuberculosis, M. avium andM. bovis BCG cultures were also exposed to different doses of NAC with or without medium pH adjustment to control for acidity. The anti-mycobacterial effect of NAC was assessed inM. tuberculosis infected human THP-1 cells and bone marrow-derived macrophages from mice lacking a fully functional NADPH oxidase system. The capacity of NAC to controlM. tuberculosis infection was further tested in vivo in a mouse (C57BL/6) model. Results PTB patients exhibited elevated levels of oxidation products and a reduction of anti-oxidants compared with LTBI cases or uninfected controls. NAC treatment inM. tuberculosis -infected human macrophages resulted in a decrease of oxidative stress and cell death evoked by mycobacteria. Importantly, we observed a dose-dependent reduction in metabolic activity and in vitro growth of NAC treatedM. tuberculosis, M. avium andM. bovis BCG. Furthermore, anti-mycobacterial activity in infected macrophages was shown to be independent of the effects of NAC on the host NADPH oxidase system in vitro. Short-term NAC treatment ofM. tuberculosis infected mice in vivo resulted in a significant reduction of mycobacterial loads in the lungs. Conclusions NAC exhibits potent anti-mycobacterial effects and may limitM. tuberculosis infection and disease both through suppression of the host oxidative response and through direct antimicrobial activity.