A team of researchers from Case Western Reserve University School of Medicine’s Department of Pharmacology recently conducted a study to better understand how essential transport proteins function in Mycobacterium smegmatis, a model organism used to study tuberculosis-related bacteria.
Their findings are expected to be published next month in Science Advances in an article titled “Structures of MmpL complexes reveal the assembly and mechanism of this family of transporters.”
Researchers of the team included faculty members Zhemin Zhang and Edward W. Yu, postdoctoral scholar Rakesh Maharjan, PhD student William D. Gregor and research associate Philip A. Klenotic.
About the study
Tuberculosis (TB), an airborne infectious disease, is caused by the causative agent Mycobacterium tuberculosis (Mtb). It has returned to being the leading cause of death from a single infectious agent, after being briefly replaced by the coronavirus during the COVID-19 pandemic. In 2023, it was estimated that 10.8 million people fell ill with TB and approximately 1.25 million patients died from this disease worldwide.
TB is currently the leading cause of death, exceeding both malaria and HIV/AIDS and causing almost twice as many deaths as the latter. To date, approximately one-third of the world’s population is infected by Mtb with most having the latent form of disease; however, approximately 10% of this population will progress to active TB.
The cell envelope of Mtb appears to be the most complex membranes of all bacteria and plays a dominant role in Mtb’s pathogenesis and virulence. The mycobacterial membrane protein large (MmpL) transporters are major contributors to mycobacterial cell wall biogenesis. The genome of Mtb encodes 13 MmpL transporters, with many engaged in the export of fatty acids and lipid components to the mycobacterial cell envelope.
