Associate Prof Kevin Pethe

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Associate Professor Kevin Pethe
PhD
Associate Professor of Infectious Disease
Email: kevin.pethe@ntu.edu.sg
Principal Investigator, Microbiology and Systems Biology Laboratory

 
 
 

Laboratory Staff
  • Michelle Ang Lay Teng, Research Assistant
  • Lim Hui Wen, Research Assistant
  • Nurlilah Binte Ab Rahman, Research Assistant
  • Ting Hui Jun, Research Assistant
  • Sangeeta Susan Thomas, Research Assistant
 
Introduction
Assoc Prof Kevin Pethe is an Associate Professor of Infectious Diseases in Lee Kong Chian School of Medicine, Nanyang Technological University.
He obtained his PhD in genetics and molecular biology from Institut Pasteur, Lille II, and received his postdoctoral training in cellular microbiology at Cornell University.

In 2004, Dr Pethe was appointed senior research investigator and project manager at the Novartis Institut for Tropical Diseases, Singapore, to work on small molecule drug discovery for tuberculosis. In 2011, he took a position of principal investigator at Institut Pasteur Korea to pursue his interest on host-pathogen interactions and chemical biology applied to tuberculosis and multidrug resistant bacteria. He was promoted to head of the department of disease biology & chemical genomics in 2013 and nominated acting CEO of Institut Pasteur Korea in the same year.
Dr Kevin Pethe is recognised for his contribution to the area of chemical genomics and drug discovery for tuberculosis. He has provided fundamental insights into the pathogenesis of Mycobacterium tuberculosis and on strategies to discover novel antibacterial agents.
His professional experience includes evaluating research grants for the European Union and the French National Research Agency. He is a former director of the board of Institut Pasteur Korea and former member of a selection committee for the appointment of principal investigators at the Institut for Basic Science, Korea.
Research Focus

The research interest of the team is focused on the strategies that pathogens use to attack and exploit hosts, and how hosts defend themselves against those attacks. A primary goal of the laboratory is to understand how bacteria adapt their metabolism and energy production mechanisms to exploit the nutritional resources of the host for growth and persistence. We believe that an in depth understanding of the bacterial metabolic circuits, required to establish infection in vivo, is also a requirement for the development of innovative strategies to control disease progression.
We are also interested in characterising metabolic synthetic lethal genetic interactions in bacteria. Several new lines of evidence suggest that a combination of weakly active chemical entities can result in a potent synergistic drug combination against multidrug resistant bacteria, revealing the existence of numerous synthetic-lethal genetic interactions. We are using a chemical genomics approach to decipher how a slight perturbation of multiple metabolic pathways can lead to a collapse of an entire biological system and to exploit this knowledge to develop novel antibacterial drug combinations.
A related interest of the lab is to study the system-level perturbation induced by antibiotics. Recent findings suggest that antibiotic-induced cell death is not directly linked to the inhibition of the primary target but to a collapse of central metabolism. We thus seek to elucidate the mechanisms behind antibacterial induced cell-death using a multidisciplinary approach combining functional genomics, chemical biology, genetics and biochemistry.
Publications

1. Pethe K*, Bifani P, Jang Jichan et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. (2013). Nat Med. 19, 1157-60. *Corresponding author.
2. Phong WY, Lin W, Rao SP, Dick T, Alonso S, Pethe K. Characterization of phosphofructokinase activity in Mycobacterium tuberculosis reveals that a functional glycolytic carbon flow is necessary to limit the accumulation of toxic metabolic intermediates under hypoxia. (2013). PloS One. 8 (2):e56037
3. Mak AP, Srinivasa PS Rao, Tan MP, Lin X, Chyba J, Tay J, Ng SH, Tan BH, Cherian J, Duraiswamy J, Bifani P, Lim V, Lee BH, Ma NL, Beer B, Thayalan P, Kelli Kuhen K, Chatterjee A, Supek F, Glynne R, J, Boshoff HI, Barry CE 3rd, Dick T, Pethe K*, and Camacho LR*. A high throughput screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis. (2012). ACS Chem Biol. 7, 1190-7. *Corresponding authors.
4. Pethe K*, Sequeira PC, Agarwalla S, Rhee K, et al. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source dependent growth inhibitors devoid of in vivo efficacy.(2010). Nat Commun. 1, 1-8. * Corresponding author.
5. Rao SP, Alonso S, Rand L, Dick T, Pethe K. The protonmotive force is required for maintaining ATP homeostasis and viability of hypoxic, nonreplicating Mycobacterium tuberculosis. (2008). Proc Natl Acad Sci, U S A. 105, 11945-50.
6. Pethe K, Swenson DL, Alonso S, Anderson J, Wang C, Russell DG. Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosome maturation. (2004). Proc Natl Acad Sci, U S A. 101, 13642-47.
7. Temmerman S*, Pethe K*, Alonso S,  Parra M, Pickett T, Drowart A, Debrie AS, Menozzi FD, C., Sergheraert C, Brennan MJ, Mascart F and Locht C. Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin. (2004). Nat Med. 10, 935-41. * Equal contribution.
8. Pethe K, Bifani P, Drobecq H, Sergheraert C, Debrie AS, Locht C, Menozzi FD. Mycobacterial heparin-binding hemagglutinin and laminin-binding protein share antigenic methyllysines that confer resistance to proteolysis. (2002). Proc Natl Acad Sci, U S A. 99, 10759-64.
9. Pethe K, Alonso S, Biet F, Delogu G, Brennan MJ, Locht C, Menozzi FD. The mycobacterial heparin-binding haemagglutinin adhesin is required for extrapulmonary dissemination. (2001). Nature. 412, 190-194.
10. Pethe K, Aumercier M, Fort E, Gatot C, Locht C, Menozzi FD. Characterization of the heparin-binding site of the mycobacterial heparin-binding hemagglutinin adhesin. (2000). J Biol Chem. 275,14273-80.