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MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections.
Sethiya, Jigar P; Sowards, Melanie A; Jackson, Mary; North, Elton Jeffrey.
  • Sethiya JP; Department of Pharmacy Sciences, School of Pharmacy & Health Professions, Creighton University, Omaha, NE 68178, USA.
  • Sowards MA; Department of Pharmacy Sciences, School of Pharmacy & Health Professions, Creighton University, Omaha, NE 68178, USA.
  • Jackson M; Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
  • North EJ; Department of Pharmacy Sciences, School of Pharmacy & Health Professions, Creighton University, Omaha, NE 68178, USA.
Int J Mol Sci ; 21(17)2020 Aug 27.
Article in English | MEDLINE | ID: covidwho-831264
Semantic information from SemMedBD (by NLM)
1. Nontuberculous Mycobacteria CAUSES Infection
Subject
Nontuberculous Mycobacteria
Predicate
CAUSES
Object
Infection
2. Current Therapy TREATS Mycobacterium Infection
Subject
Current Therapy
Predicate
TREATS
Object
Mycobacterium Infection
3. Plasma membrane PRODUCES Mycolic Acids
Subject
Plasma membrane
Predicate
PRODUCES
Object
Mycolic Acids
4. Membrane LOCATION_OF Mycolic Acids
Subject
Membrane
Predicate
LOCATION_OF
Object
Mycolic Acids
5. Nontuberculous Mycobacteria CAUSES Infection
Subject
Nontuberculous Mycobacteria
Predicate
CAUSES
Object
Infection
6. Current Therapy TREATS Mycobacterium Infections, Nontuberculous
Subject
Current Therapy
Predicate
TREATS
Object
Mycobacterium Infections, Nontuberculous
7. Plasma membrane PRODUCES Mycolic Acids
Subject
Plasma membrane
Predicate
PRODUCES
Object
Mycolic Acids
8. Membrane LOCATION_OF Mycolic Acids
Subject
Membrane
Predicate
LOCATION_OF
Object
Mycolic Acids
ABSTRACT
Outside of Mycobacterium tuberculosis and Mycobacterium leprae, nontuberculous mycobacteria (NTM) are environmental mycobacteria (>190 species) and are classified as slow- or rapid-growing mycobacteria. Infections caused by NTM show an increased incidence in immunocompromised patients and patients with underlying structural lung disease. The true global prevalence of NTM infections remains unknown because many countries do not require mandatory reporting of the infection. This is coupled with a challenging diagnosis and identification of the species. Current therapies for treatment of NTM infections require multidrug regimens for a minimum of 18 months and are associated with serious adverse reactions, infection relapse, and high reinfection rates, necessitating discovery of novel antimycobacterial agents. Robust drug discovery processes have discovered inhibitors targeting mycobacterial membrane protein large 3 (MmpL3), a protein responsible for translocating mycolic acids from the inner membrane to periplasm in the biosynthesis of the mycobacterial cell membrane. This review focuses on promising new chemical scaffolds that inhibit MmpL3 function and represent interesting and promising putative drug candidates for the treatment of NTM infections. Additionally, agents (FS-1, SMARt-420, C10) that promote reversion of drug resistance are also reviewed.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Membrane Transport Proteins / Anti-Bacterial Agents / Nontuberculous Mycobacteria / Mycobacterium Infections, Nontuberculous Type of study: Observational study Limits: Humans Language: English Year: 2020 Document Type: Article Affiliation country: Ijms21176202

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Membrane Transport Proteins / Anti-Bacterial Agents / Nontuberculous Mycobacteria / Mycobacterium Infections, Nontuberculous Type of study: Observational study Limits: Humans Language: English Year: 2020 Document Type: Article Affiliation country: Ijms21176202