1) Research focus

Towards understanding the immunochemistry of cell wall mycolic acids in tuberculosis

2) Research leaders

Prof Jan Verschoor 

3) Collaborators

Prof M Baird (University of Wales, UK), Prof Johan Grooten (Gent University, Belgium), Prof C de Chastellier (Centre d’Immunologie de Marseille-Luminy, France), Dr Yolandy Lemmer (CSIR, South Africa).

4) Background

Mycobacterial cell wall mycolic acids (MA) are known to play an important role in the pathogen - host macrophage interaction that precedes manifestation of tuberculosis (TB) and subsequently in sustaining the disease by nurturing the persistent stage of mycobacterial infection in or outside of the macrophages in the TB granulomas. How the three functional classes of MA (alpha-, keto- and methoxy-MA) differentially contribute to this is largely unknown. Insight in how this happens is likely to reveal novel ways whereby TB can be diagnosed, prevented and/or cured. With our collaborators at University of Bangor, UK, we were involved in the first stereo-controlled chemical synthesis of the various mycolic acid classes and have prepared the first combinatorial monoclonal antibodies with mycolic acid specificities as powerful tools to investigate this. This is reviewed in our pioneering work “Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis” that was published in 2012 in “Progress in Lipid Research”.

5) Current research activities/developments

Our current research revolves around recombinant antibodies against mycolic acids for their use in TB diagnostics as well as immunocytochemistry to evaluate the role that mycolic acids play in tuberculosis disease progression and manifestation. Structure function studies are facilitated by collaborations with the University of Bangor in the UK, who supply us with stereo-controlled chemically synthetic mycolic acids of all functional types.

A university start-up company was established in 2014 to undertake the further development and clinical trials of the MARTI-TB test that was developed by the team of students and staff in department of Biochemistry.

6) Research objectives

We apply these skills and tools to (1) determine the composition of MA antigens in the early and late stages of TB in in vitro mycobacterial culture and in infected guinea pigs, (2) determine the preferred MA composition to serologically distinguish between human TB and control patient sera, (3) investigate MA as targeting ligand on anti-TB drug loaded PLGA nanoparticles to effect targeted uptake by M. tuberculosis infected human and mouse macrophage cell cultures and maintain the mycobacteria in the active, replicating state to increase their susceptibility to the antibiotics.