Heteroresistance in Mycobacterium tuberculosis: from molecular mechanisms and advanced detection to clinical implications.

Drug resistance in Mycobacterium species, particularly Mycobacterium tuberculosis, remains a protracted and severe challenge to global public health. Recent studies have revealed that heteroresistance, serving as a critical precursor stage to full resistance, plays a pivotal role in treatment failure and disease relapse. Heteroresistance is characterized by the co-existence of susceptible and resistant subpopulations within a single bacterial population; however, due to the low proportion of the resistant subpopulation, it is highly susceptible to being missed in routine clinical diagnosis. This review summarizes the genetic and phenotypic mechanisms underlying the emergence of heteroresistance in Mycobacterium tuberculosis, evaluates the utility of various molecular detection technologies in identifying heteroresistance, and discusses its impact on clinical treatment regimen adjustments and the evolutionary trajectory of drug resistance. Ultimately, this review aims to provide a theoretical foundation for optimizing individualized, precision treatment for patients infected with Mycobacterium tuberculosis.