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Updated: Aug 24, 2026

An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis
Published on: August 16, 2021
Tubercle bacilli generate a novel cell wall-associated pigment after long-term anaerobic culture
Adam F Cunningham1, Peter R Ashton, Claire L Spreadbury
1Birmingham Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, UK. a.f.Cunningham@bham.ac.uk
Abstract:
Many cases of tuberculosis result from reactivation of previously acquired latent infections. Models to study such persister forms often involve gradual depletion of oxygen during culture as poor aeration is a characteristic of non-progressive TB granulomas. Anaerobically cultured bacilli develop a thickened outer-most cell wall layer. Here, we analyzed this layer from anaerobically cultured Mycobacterium tuberculosis and Mycobacterium bovis BCG. By six weeks of anaerobiosis a pigment was detected at levels > 60-fold higher in anaerobic than aerobic bacilli. This pigment was responsible for the electron-dense appearance of the thickened cell wall layer and gave an electrospray mass spectrometry peak at 409 Da (M+Na)+ or (M+H)+. We termed this pigment APP1, anaerobically produced pigment 1, the first pigment identified in M. tuberculosis.
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