한빛사 논문
Jae Jin Lee1,6, Sun-Kyung Lee2,6, Naomi Song3, Temitope O. Nathan4, Benjamin M. Swarts4, Seok-Yong Eum2, Sabine Ehrt3, Sang-Nae Cho2,5 & Hyungjin Eoh1,*
1 Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. 2 Division of Immunopathology and Cellular Immunology, International Tuberculosis Research Center, Changwon 51755, Republic of Korea. 3 Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA. 4 Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI 48859, USA. 5 Department of Microbiology and Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. 6These authors contributed equally: Jae Jin Lee, Sun-Kyung Lee.
*Correspondence and requests for materials should be addressed to H.E.
Abstract
Stochastic formation of Mycobacterium tuberculosis (Mtb) persisters achieves a high level of antibiotic-tolerance and serves as a source of multidrug-resistant (MDR) mutations. As conventional treatment is not effective against infections by persisters and MDR-Mtb, novel therapeutics are needed. Several approaches were proposed to kill persisters by altering their metabolism, obviating the need to target active processes. Here, we adapted a biofilm culture to model Mtb persister-like bacilli (PLB) and demonstrated that PLB underwent trehalose metabolism remodeling. PLB use trehalose as an internal carbon to biosynthesize central carbon metabolism intermediates instead of cell surface glycolipids, thus maintaining levels of ATP and antioxidants. Similar changes were identified in Mtb following antibiotic-treatment, and MDR-Mtb as mechanisms to circumvent antibiotic effects. This suggests that trehalose metabolism is associated not only with transient drug-tolerance but also permanent drug-resistance, and serves as a source of adjunctive therapeutic options, potentiating antibiotic efficacy by interfering with adaptive strategies.
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