Heteroresistance of tuberculosis: Mechanism, detection, and clinical treatment

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, has remained a persistent threat to global public health. Heteroresistance, a unique and complex form of TB drug resistance, refers to the co-existence of drug-resistant and drug-susceptible subpopulations within a host. This review aims to summarize the molecular mechanisms, detection methods, and targeted therapeutic strategies associated with TB heteroresistance.

PubMed was searched through both key terms and subject headings. The literatures were screened, assessed for the quality, and evidence synthesized.

Heteroresistance arises from mixed infections or clonal heterogeneity under drug pressure, affecting multiple anti‑TB drugs with widely varying mutant proportions. Conventional phenotypic tests are slow and insensitive, whereas advanced molecular assays enable reliable detection of low‑abundance resistant subpopulations. Heteroresistance correlates with discordant susceptibility results, delayed treatment response, and poorer outcomes, especially in immunocompromised patients, though optimized combination regimens may offer benefit.

Incorporating heteroresistance evaluation and high‑sensitivity molecular diagnostics into clinical algorithms is critical to prevent progression to full resistance. Future work should focus on standardized surveillance and broader access to these technologies to effectively curb drug‑resistant TB.