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Kevin Pethe

Associate Professor Kevin Pethe
Assistant Dean, Research
Associate Professor of Infectious Disease
Principal Investigator, Microbiology and Systems Biology Laboratory​​
Research Programmes: Microbiome Medicine​;
Respiratory & Infectious Diseases


  • Nurlilah Binte Ab Rahman, Research Assistant
  • Sangeeta Susan Thomas, PhD Student
  • Bei Shi Lee, PhD Student
  • Ria Sorayah, PhD Student
  • Benny Yeo, PhD Student
  • Ting Lim, PhD Student
  • Ekaterina Sviryaeva, PhD Student
  • Nitin Kalia, Research Fellow


Associate Professor Kevin Pethe is the Assistant Dean for Research and 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, A/Prof Pethe was appointed senior research investigator and project manager at the Novartis Institute 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. 

A/Prof 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, on microbial bioenergetics, 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.

Selected Publications


Kalia NP, Hasenoehrl EJ, ... Pethe K. (2017). Exploiting the synthetic lethality betweenterminal respiratory oxidases to kill M. tuberculosis and clear host infection. Proceedings of the National Academy of Sciences. 114(28):7426-31.

Murima P, Zimmermann M, ... Pethe K, et al. (2016). A rheostat mechanism governs the bifurcation of carbonflux in mycobacteria.  Nature Communications. 7:12527.

Pethe K, Bifani P, Jang J, et al. (2013). Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nature Medicine. 19(9);1157-60.

Mak PA, Srinivasa PSR, ... Pethe K, et al. (2012)A high throughput screen to identify inhibitors of ATP homeostasis innon-replicating Mycobacterium tuberculosis.  ACS Chemical Biology. 7(7);1190-7.

Pethe K, Sequeira PC, Agarwalla S, et al. (2010). A chemical genetic screen inMycobacterium tuberculosis identifies carbon-source dependent growth inhibitorsdevoid of in vivo efficacy. Nature Communications. 1:57.

Rao SP, Alonso S, ... Pethe K. (2008). The protonmotive force is required formaintaining ATP homeostasis and viability of hypoxic, nonreplicating Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences. 105(33);11945-50.

Pethe K, Swenson DL, Alonso S, et al. (2004). Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosomematuration. Proceedings of the National Academy of Sciences of the United States of America, 101(37), 13642-7. 

Temmerman S, Pethe K, Alonso S,  et al. (2004). Methylation-dependent Tcell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin. Nature Medicine. 10(9);935-41.

Pethe K, Bifani P, Drobecq H, et al. (2002). Mycobacterial heparin-binding hemagglutinin and laminin-binding protein shareantigenic methyllysines that confer resistance to proteolysis. Proceedings of the National Academy of Sciences. 99(16);10759-64. 

Pethe K, Alonso S, Biet F, et al. (2001). The my​cobacterialheparin-binding haemagglutinin adhesion is required for extrapulmonarydissemination. Nature. 412(6843);190-4.

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