Mycobacterium avium complex (MAC) species are the most commonly isolated nontuberculous mycobacteria to cause pulmonary infections worldwide. The lengthy and complicated therapy required to cure lung disease due to MAC is at least in part due to the phenomenon of antibiotic tolerance. In this review, we will define antibiotic tolerance and contrast it with persistence and antibiotic resistance. We will discuss physiologically relevant stress conditions that induce altered metabolism and antibiotic tolerance in mycobacteria. Next, we will review general molecular mechanisms underlying bacterial antibiotic tolerance, particularly those described for MAC and related mycobacteria, including Mycobacterium tuberculosis, with a focus on genes containing significant sequence homology in MAC. An improved understanding of antibiotic tolerance mechanisms can lay the foundation for novel approaches to target antibiotic-tolerant mycobacteria, with the goal of shortening the duration of curative treatment and improving survival in patients with MAC.
The prolonged treatment required to eradicate
Mycobacterium avium
complex (MAC) infection is likely due to the presence of subpopulations of antibiotic-tolerant bacteria with reduced susceptibility to currently available drugs. However, little is known about the genes and pathways responsible for antibiotic tolerance in MAC.
of an isopotential point at Ed -0.03-0.05 V in the purified HCIO4, both in the successive cathodic and anodic disk potential scans. These IP's are surprisingly well developed. As has been shown by electrochemical mass spectrometry (38), an unknown organic impurity is adsorbed when the Pt disk electrode is held more cathodic than 0.5 V. This organic species can be desorbed simultaneously with the adsorption of strongly bonded adsorbed H, resulting in the IP in the cathodic scan. Seemingly, this impurity starts adsorbing with the desorption of H in the anodic disk electrode scan, = 0 rpm, resulting in the IP in the anodic disk scan. In unelectrolyzed solutions, especially at higher concentrations of HCIO4, simultaneous reduction/oxidation of other electroactive impurities interferes and IP's are either illdeveloped or disappear.The results of the above experiments showed that the commercially available oxyacids and NaOH we studied contain impurities which can be deposited on a Pt electrode at 0.5 < < -0.2 V. These impurities prevent Hadsorption, inhibit oxygen reduction, and can be oxidized simultaneously with Pt. However, these impurities can rapidly be removed by passing the solution through a bed of reduced Pt sponge held at a potential slightly anodic of bulk hydrogen evolution.
ACKNOWLEDGMENTThe cooperation of J. Comeau in performing and evaluating the electrochemical mass spectrometric study is acknowledged.
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