Alain Filloux


Alain Ange-Marie Filloux is a French/British microbiologist who is the director of the Singapore Centre for Environmental Life Sciences Engineering and a professor of molecular microbiology at Nanyang Technological University, Singapore. He holds joint appointments at both the School of Biological Sciences and the Lee Kong Chian School of Medicine at NTU. His research looks at the chronic infection of Pseudomonas aeruginosa, a Gram-negative bacterium that causes nosocomial infections in people who are immunocompromised and a deadly threat for cystic fibrosis patients. He is a visiting professor at Imperial College London.

Education

Filloux was a graduate student at Universite d'Aix-Marseille II, where he started to study protein secretion in Pseudomonas aeruginosa. He obtained his doctorate under the supervision of Andrée Lazdunski in 1988 and with the support of a European Union fellowship moved to the Netherlands for his postdoctoral research, where he joined Utrecht University and the laboratory of Dr Jan Tommassen.

Research and career

In 1990, Filloux became assistant professor at Utrecht University, and continued to explore protein secretion in Gram-negative bacteria. He identified that a common mechanism is responsible for the transport of macromolecules across the outer membrane of Gram-negative bacteria that includes Pseudomonas aeruginosa. In particular he co-discovered what is now called the type II secretion system. This finding contributed to understanding protein secretion systems in Gram-negative bacteria, which are essential to their pathogenicity.
In 1994, Filloux was appointed to the French National Centre for Scientific Research as a research associate. In 2001, he became research director and headed his laboratory on "Molecular Microbiology and Pathogenicity in Pseudomonads". Filloux became director of the CNRS research unit Laboratoire d’Ingénierie des Systèmes Macromoléculaires in 2003. Filloux became increasingly interested in the ability that allows bacteria to live on a surface or tissues as a resilient community known as biofilm. Biofilms are intrinsically resistant to eradication by antibiotics or the immune system, and present a major issue in healthcare. He used bacterial genetics to identify a series of molecular determinants involved in the biofilm formation process, notably extracellular appendages, or fimbriae, he called Cup. Working with Stephen Lory from Harvard Medical School, Filloux discovered a regulatory switch, LadS, which allows Pseudomonas aeruginosa to transition from planktonic to a biofilm.
In 2007 he joined Imperial College London as professor and chair of the Centre for Molecular Bacteriology and Infection. Filloux continued to work on protein secretion systems, but concentrated his research on the so-called Type VI secretion system, a molecular crossbow that delivers toxins in competing bacterial competitors and kills them. He discovered many T6SS toxins in Pseudomonas aeruginosa and described how these could be transported in target bacteria notably by being placed at the tip of the molecular arrowhead.
One such example is VgrG2b, which contains a metallopeptidase domain targeting, in the prey bacteria, proteins involved in cell wall integrity and cell division. Bacterial preys will then collapse, as they do for example when treated with Βeta-lactam antibiotics. Filloux also carried on studying biofilms, and gained interest in a central switch which involves the universal second messenger cyclic-di-GMP. It was known that high levels of c-di-GMP in bacterial cells turns on biofilm development, and Filloux showed that concomitantly high c-di-GMP levels turned on the T6SS. This suggested that the T6SS is put in place when cells enter a phase allowing polymicrobial communities to establish and is thus prepared to eliminate foes.
While continuing to study protein secretion and biofilm formation, Filloux started to investigate antibiotic resistance. He collaborated with Gerald Larrouy-Maumus on the development of a protocol for rapid antibiotic resistance screening using mass spectrometry.
In 2022, Filloux was appointed as the centre director of SCELSE in Singapore, where he continues to explore biofilm formation and bacterial secretion systems.

Membership and editorial boards

Filloux has been an editor for several scientific journals. He was editor-in-chief for FEMS Microbiology Reviews and for npj Biolfilms and Microbiomes '', which is part of the Nature Partner Journals'' series.
Filloux has held scientific administrative positions including membership of the BBSRC - Research Grants Committee B, the MRC Infection and immunity board, the FWO panel Medical Microbiology. He was also chair of the ANR scientific committee on microbiology, immunology and infection.

Awards and honours

Selected academic works

Publications

  • Fecht, S.; Paracuellos, P.; Subramoni, S.; Tan, C. A. Z.; Ilangovan, A.; Costa, T. R. D.; Filloux, A.. "". Nature Communications. 15 : 4283. doi:10.1038/s41467-024-48487-8. PMID 38769318.
  • Rudzite, M.; Subramoni, S.; Endres, R. G.; Filloux, A.. "". PLOS Pathogens. 19 : e1011428. doi:10.1371/journal.ppat.1011428. PMID 37253075.
  • Nolan, L. M.; Cain, A. K.; Clamens, T.; Furniss, R. C. D.; Manoli, E.; Sainz-Polo, M. A.; Dougan, G.; Albesa-Jové, D.; Parkhill, J.; Mavridou, D. A. I.; Filloux, A.. "". Nature Microbiology. 6 : 1199–1210. doi:10.1038/s41564-021-00950-8. PMID 34413503.
  • Bernal, P.; Furniss, R. C. D.; Fecht, S.; Leung, R. C. Y.; Spiga, L.; Mavridou, D. A. I.; Filloux, A.. "". Proceedings of the National Academy of Sciences of the United States of America. 118 : e2008500118. doi:10.1073/pnas.2008500118. PMID 33558227.
  • Wood, T. E.; Howard, S. A.; Förster, A.; Nolan, L. M.; Manoli, E.; Bullen, N. P.; Yau, H. C. L.; Hachani, A.; Hayward, R. D.; Whitney, J. C.; Vollmer, W.; Freemont, P. S.; Filloux, A.. "". Cell Reports. 29 : 187–201.e7. doi:10.1016/j.celrep.2019.08.094. PMID 31577948.
  • Valentini, M.; Filloux, A.. "". Annual Review of Microbiology. 73: 387–406. doi:10.1146/annurev-micro-020518-115555. PMID 31500536.
  • Pissaridou, P.; Allsopp, L. P.; Wettstadt, S.; Howard, S. A.; Mavridou, D. A. I.; Filloux, A.. "T". Proceedings of the National Academy of Sciences of the United States of America. 115 : 12519–12524. doi:10.1073/pnas.1814181115. PMID 30455305.
  • Dortet, L.; Lombardi, C.; Cretin, F.; Dessen, A.; Filloux, A.. "". Nature Microbiology. 3 : 378–386. doi:10.1038/s41564-018-0109-7. PMID 29403015.
  • Valentini, M.; Gonzalez, D.; Mavridou, D. A.; Filloux, A.. "". Current Opinion in Microbiology. 41: 15–20. doi:10.1016/j.mib.2017.11.006. PMID 29166621.
  • Allsopp, L. P.; Wood, T. E.; Howard, S. A.; Maggiorelli, F.; Nolan, L. M.; Wettstadt, S.; Filloux, A.. "". Proceedings of the National Academy of Sciences of the United States of America. 114 : 7707–7712. doi:10.1073/pnas.1700286114. PMID 28673999.
  • McCarthy, R. R.; Mazon-Moya, M. J.; Moscoso, J. A.; Hao, Y.; Lam, J. S.; Bordi, C.; Mostowy, S.; Filloux, A.. "". Nature Microbiology. 2: 17027. doi:10.1038/nmicrobiol.2017.27. PMID 28263305.
  • Valentini, M.; Laventie, B. J.; Moscoso, J.; Jenal, U.; Filloux, A.. "". PLOS Genetics. 12 : e1006354. doi:10.1371/journal.pgen.1006354. PMID 27792789.
  • Planamente, S.; Salih, O.; Manoli, E.; Albesa-Jové, D.; Freemont, P. S.; Filloux, A.. "". EMBO Journal. 35 : 1613–1627. doi:10.15252/embj.201694024. PMID 27288401.
  • Valentini, M.; Filloux, A.. "". Journal of Biological Chemistry. 291 : 12547–12555. doi:10.1074/jbc.R115.711507. PMID 27129226.
  • Hachani, A.; Wood, T. E.; Filloux, A.. "". Current Opinion in Microbiology. 29: 81–93. doi:10.1016/j.mib.2015.11.006. Epub 2015 Dec 24. PMID 26722980.
  • Hachani, A.; Allsopp, L. P.; Oduko, Y.; Filloux, A.. "". Journal of Biological Chemistry. 289 : 17872–17884. doi:10.1074/jbc.M114.563429. Epub 2014 May 2. PMID 24794869.
  • Filloux, A.. "". Nature. 500 : 284–285. doi:10.1038/nature12545. Epub 2013 Aug 7. PMID 23925115.
  • Moscoso, J. A.; Mikkelsen, H.; Heeb, S.; Williams, P.; Filloux, A.. "". Environmental Microbiology. 13 : 3128–3138. doi:10.1111/j.1462-2920.2011.02595.x. Epub 2011 Sep 29. PMID 21955777.
  • Garvis, S.; Munder, A.; Ball, G.; de Bentzmann, S.; Wiehlmann, L.; Ewbank, J. J.; Tümmler, B.; Filloux, A.. "". PLoS Pathogens. 5 : e1000540. doi:10.1371/journal.ppat.1000540. Epub 2009 Aug 7. PMID 19662168.
  • Filloux, A.. "". Biochimica et Biophysica Acta. 1694: 163–179. doi:10.1016/j.bbamcr.2004.05.003. PMID 15546665.
  • Voulhoux, R.; Ball, G.; Ize, B.; Vasil, M. L.; Lazdunski, A.; Wu, L. F.; Filloux, A.. "". EMBO Journal. 20 : 6735–6741. doi:10.1093/emboj/20.23.6735. PMID 11726509.
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Books

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