Mycobacterium tuberculosis borderline rpoB mutations: emerging from the unknown. Issue 3 (2nd September 2021)

• Record Type: Journal Article
• Authors: Van Deun, Armand; Decroo, Tom; Aung, Kya Jai Maug; Hossain, Mohamed Anwar; Gumusboga, Mourad; De Rijk, Willem Bram; Tahseen, Sabira; de Jong, Bouke Catherine; Rigouts, Leen
• Is Part Of: European respiratory journal. Volume 58:Issue 3(2021)
• Publication Date: 2021-09-02
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.00783-2021
• Languages: English
• ISSNs: 0903-1936

Abstract

Rifampicin drives the efficacy of the current first-line treatment regimen for tuberculosis (TB) [1]. Mutations in the rpoB gene cause rifampicin resistance (RR) of varying levels. Common mutations typically confer high-level, "high-confidence" resistance, providing a selective advantage to Mycobacterium tuberculosis during treatment at low fitness cost [2]. Growth-based phenotypic drug-susceptibility testing (pDST) is very reliable for high-confidence mutations. Mutations conferring low-level resistance at high fitness cost are easily lost during primary culture or will cause phenotypically false-susceptible results if not given enough time for growth, especially with the widely used automated MGIT 960 DST [3]. Due to disagreement on their significance, such rpoB mutations were called "disputed". Despite their name, borderline rpoB mutations are correlated with unfavourable outcomes when rifampicin-throughout treatment is used. They may become the drivers of rifampicin-resistant tuberculosis. Second-line treatment is recommended. https://bit.ly/3nbkZjt