Research Projects

Antimicrobial resistance (AMR) is a significant threat to human health, causing 1.27 million deaths in 2016 and an estimated 10 million deaths annually by 2050. Nontuberculous mycobacteria (NTM) infections, which are lethal in immunocompromised individuals, are also a concern due to the rise in AMR. High levels of intrinsic drug resistance and lengthy treatment regimens contribute to AMR in NTM. Targeting these mechanisms can increase the potency of antibiotics, suggesting co-therapy with inhibitors targeting intrinsic drug resistance can be an effective strategy in controlling mycobacterial infections. A study has identified an extra-cytoplasmic sigma factor sigH1 in Mycobacterium smegmatis, which was overexpressed in response to multiple antibiotics. The study aims to identify the sigH1 regulated gene(s) or pathway(s) that enable intrinsic drug resistance. Cell wall permeability and biofilm forming abilities of wild type, mutant, and complement strains will be compared, followed by relative gene expression analysis using RNA sequencing and qRT-PCR. This identification is critical in understanding the mechanism of intrinsic drug resistance in NTM and developing inhibitors to increase their potency and potentially reduce treatment duration.