Transient drug-tolerance and permanent drug-resistance rely on the trehalose-catalytic shift in Mycobacterium tuberculosis

• DOI: 10.1038/s41467-019-10975-7
• Publication Date: 2019-07-02T10:02:56Z
• Authors: Jae Jin Lee; Sun-Kyung Lee; Naomi Song; Temitope O. Nathan; Benjamin M. Swarts; Seok-Yong Eum; Sabine Ehrt; Sang-Nae Cho; Hyungjin Eoh
• Keywords: Drug tolerance; Multidrug tolerance; Efflux

Abstract Stochastic formation of Mycobacterium tuberculosis (Mtb) persisters achieves a high level antibiotic-tolerance and serves as source multidrug-resistant (MDR) mutations. As conventional treatment is not effective against infections by MDR-Mtb, novel therapeutics are needed. Several approaches were proposed to kill altering their metabolism, obviating the need target active processes. Here, we adapted biofilm culture model Mtb persister-like bacilli (PLB) demonstrated that PLB underwent trehalose metabolism remodeling. use an internal carbon biosynthesize central intermediates instead cell surface glycolipids, thus maintaining levels ATP antioxidants. Similar changes identified in following antibiotic-treatment, MDR-Mtb mechanisms circumvent antibiotic effects. This suggests associated only with transient drug-tolerance but also permanent drug-resistance, adjunctive therapeutic options, potentiating efficacy interfering adaptive strategies.