A patient with multidrug-resistant tuberculosis (MDR-TB) developed resistance to bedaquiline (BDQ) and clofazimine (CFZ) during treatment. The clinical presentation involved persistent Mycobacterium tuberculosis infection despite standard therapy. Diagnostic methods included whole-genome sequencing, which identified a novel loss-of-function mutation in the pepQ gene. This genetic change was directly associated with the acquired resistance to both BDQ and CFZ, highlighting a critical mechanism of treatment failure. The case underscores the importance of genomic surveillance in guiding effective MDR-TB management and understanding emerging resistance patterns. This finding offers new insights into the molecular basis of drug resistance in M. tuberculosis.
Key note: Novel mutations in genes like pepQ can lead to simultaneous resistance to multiple critical anti-TB drugs.