Understanding the vitamin B12 transport system in Mycobacterium tuberculosis

Year of award: 2022


  • Dr Terry Kipkorir

    London School of Hygiene and Tropical Medicine , United Kingdom

Project summary

More than one million people die every year from tuberculosis (TB), an infectious respiratory disease caused by Mycobacterium tuberculosis (Mtb), a human-adapted bacterial pathogen which exhibits resistance to many currently available antibiotics. Understanding the physiological and metabolic processes enabling the success of Mtb is critical to eradicate TB. Nutrient acquisition is an important component of host defences against Mtb infection and, therefore, is a promising but underexploited area for new drug development. Coenzyme B12 (B12) is an essential cofactor in at least three metabolic pathways in Mtb, including methionine biosynthesis, nucleotide pool maintenance, and fatty acid metabolism. However, during its evolution to specialist pathogen from an environmental ancestor, Mtb lost the ability to produce B12 de novo and must therefore obtain the cofactor from its host. The mechanism(s) for B12 acquisition remain unknown, but could have significant implications for understanding the adaptation of Mtb to human colonisation and refractoriness to clearance. The study proposed here aims to identify and functionally characterise the proteins involved in B12 transport in Mtb, elucidate their cellular organisation, and investigate the regulatory mechanisms underlying their expression. These investigations will reveal the unique aspects of Mtb B12 transport that could be exploited for anti-TB drug design.