Unveiling the response of efflux pump genes to delamanid in Mycobacterium tuberculosis H37Rv: a transcriptomic...

Overexpression of efflux pumps has been associated with drug resistance in Mycobacterium tuberculosis. However, their specific role in delamanid resistance remains unclear. This study aimed to identify efflux pump genes influenced by delamanid exposure through transcriptomic analysis. Cultures of M. tuberculosis H37Rv were exposed to delamanid at a sub-inhibitory concentration of ½ MIC for 24 h and transcriptomic sequencing was performed on exposed and unexposed cultures. Differentially expressed genes (DEGs) were annotated using the UniProt database. Transcriptomic analysis revealed that 23 efflux pump genes were significantly upregulated under delamanid stress, with 17/23 (73.9%) belonging to the ABC family, 4/23 (17.39%) to the RND family and 2/23 (8.69%) to the MFS superfamily. Quantitative real-time PCR (qRT-PCR) was conducted to validate the transcriptomic results for efflux pump genes following exposure of M. tuberculosis H37Rv to delamanid at ½ and ¼ MIC. qRT-PCR confirmed that 20/23 (86.95%) genes were significantly upregulated at ½ MIC, with 14/20 (70%) of these belonging to the ABC family. In contrast, only 3/23 (13%) efflux pump genes demonstrated upregulation at ¼ MIC. This study identified a set of efflux pump genes significantly upregulated in response to sub-inhibitory concentrations of delamanid and suggested that ½ MIC is a more suitable concentration than ¼ MIC for evaluating the expression of efflux pump genes in response to delamanid in M. tuberculosis.