Congratulations to Marie Haufroid and Elise Pierson who presented the “Best Communication” at the Journées Franco-Belges de Pharmacochimie 2017

The Laboratory of Structural Biological Chemistry (CBS) led by Prof. Johan Wouters is involved in the search for new anti-tuberculosis targets and drugs. PhD student Marie Haufroid and master student Elise Pierson conduct a structural and inhibition study of SerB2, an enzyme of Mycobacterium tuberculosis, known to be a virulence factor and to be essential for bacterial survival.

On the occasion of the “Journées Franco-Belges de Pharmacochimie” 2017, Marie Haufroid and Elise Pierson presented a poster entitled "Study of the inhibition of Mycobacterium tuberculosis SerB2 (phosphoserine phosphatase): identification of new potential inhibitors" (see abstract). Moreover, Marie Haufroid delivered a 3-min speech about their research in front of a jury composed of members of the organizing committee. The jury awarded them the “Best Communication” prize! Thanks to this prize, the open online journal « Pharmaceuticals » offers them the possibility of a free publication of their research.

ABSTRACT

Study of the inhibition of SerB2 (Mycobacterium tuberculosis phosphoserine phosphatase)

Elise Pierson⁽¹⁾, Marie Haufroid⁽¹⁾, Johan Wouters⁽¹⁾, Ramandeep Singh⁽²⁾

(1) University of Namur (UNamur), Namur Research Institute for Life Sciences (NARILIS), Namur Medicine and Drug Innovation Center (Namedic), Laboratoire de Chimie Biologique Structurale (CBS)
(2) Vaccine and Infectious Disease Reasearch Centre, Translational Health Science and Technology Institute, Gurgaon 122016, Haryana, India

Drug-resistant tuberculosis, caused by a strain of Mycobacterium tuberculosis resistant to first and second-line drugs, is a major global health threat. ^[1-3] Treatment options being limited, the search for new anti-tuberculosis targets and drugs is therefore needed. SerB2 is known to be a virulence factor of M. tuberculosis ^[4-6] and to be essential for bacteria survival, which makes this enzyme a promising therapeutic target for tuberculosis treatment.
SerB2 is secreted into the cytoplasm of THP-1 macrophages infected by M. tuberculosis. Through its phosphatase activity, the enzyme dephosphorylates definite proteins and transcription factors, which causes microtubule rearrangement within the macrophage and deactivates the immune system of the host. SerB2 then assists the bacteria in immune invasion and evasion. ^[4-6]

The objective of this work is to inhibit SerB2, with the overall aim of reducing M. tuberculosis virulence. The starting point was to express and purify SerB2. Then, new inhibitors were identified through an enzymatic activity assay using colorimetric phosphate determination. To achieve this, a screening of previously selected small molecules of the NAMEDIC’s library was performed. This experiment led to the identification of three promising inhibitors that are harmine derivatives. Clofazimine potent inhibitory effect was also confirmed. The inhibition type of the scaffolds will be assessed by further kinetic studies and other derivatives will be synthesized and characterized.

Acknowledgment. The authors thank members of NAMEDIC who generated NAMEDIC library, in particular Prof B. Masereel and L. Pochet.

[1] S. Sarkar and M.R. Suresh. Journal of Pharmacy & Pharmaceutical Sciences, 14(2):148–161, 2011.

[2] K. Green and S. Garneau-Tsodikova. Frontiers in microbiology, 4:208, 2013.

[3] P.D.A Da Silva and J.C. Palomino. Journal of antimicrobial chemotherapy, 66(7):1417–1430, 2011.

[4] A. K. Sharma, N. Dhasmana, N. Dubey, N. Kumar, A. Gangwal, M. Gupta, and Y. Singh. Indian Journal of Microbiology, 57(1):1–10, 2017.

[5] G.P. Yadav, S. Shree, R. Maurya, N. Rai, D.K. Singh, K.K. Srivastava, and R. Ramachandran. PLoS ONE, 9(12):1–24, 2014.

[6] S. Shree, A.K. Singh, R. Saxena, H. Kumar, A. Agarwal, V.K. Sharma, K. Srivastava, K.K. Srivastava, S. Sanyal, and R. Ramachandran. Cellular and Molecular Life Sciences, 73(17):3401–3417, 2016

* Correspondence: elise.pierson@student.unamur.be