Exploration of Synergistic Action of Cell Wall-Degrading Enzymes against Mycobacterium tuberculosis

Abstract

The major global health threat tuberculosis is caused by Mycobacterium tuberculosis . M. tuberculosis has a complex cell envelope—a partially covalently linked composite of polysaccharides, peptidoglycan, and lipids, including a mycolic acid layer—which conveys pathogenicity but also protects against antibiotics. Given previous successes in treating Gram-positive and -negative infections with cell wall-degrading enzymes, we investigated such an approach for M. tuberculosis . In this study, we aimed to (i) develop an M. tuberculosis microtiter growth inhibition assay that allows undisturbed cell envelope formation to overcome the invalidation of results by typical clumped M. tuberculosis growth in surfactant-free assays, (ii) exploring anti- M. tuberculosis potency of cell wall layer-degrading enzymes, and (iii) investigate the concerted action of several such enzymes.