In 1990, Filloux was promoted to Assistant Professor at Utrecht University, and continued to explore protein secretion in Gram-negative bacteria.[2] 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.[2] In particular he co-discovered what is now called the type II secretion system (T2SS).[2] This finding contributed to understanding protein secretion systems in Gram-negative bacteria, which are essential to their pathogenicity.[2]
In 1994, Filloux was appointed to the French National Centre for Scientific Research (CNRS)[3] as a Research Associate (CR1). In 2001, he was promoted as Research Director and headed his laboratory on “Molecular Microbiology and Pathogenicity in Pseudomonads”. Filloux became the Director of the CNRS research unit Laboratoire d’Ingénierie des Systèmes Macromoléculaires in 2003.[3] 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, where he was appointed Professor and Chair of the Centre for Molecular Bacteriology and Infection.[4] Filloux continued to work on protein secretion systems, but concentrated his research on the so-called Type VI secretion system (T6SS), 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.[5]
One such example is VgrG2b, which contains a metallopeptidase domain targeting, in the prey bacteria, proteins involved in cell wall integrity and cell division.[5] Bacterial preys will then collapse, as they do for example when treated with Βeta-lactam antibiotics.[5] 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.[5]
While continuing studying protein secretion and biofilm formation, Filloux gained interest investigating antibiotic resistance.[6][7] He collaborated with Dr Gerald Larrouy-Maumus on the development of a protocol for rapid antibiotic resistance screening using mass spectrometry.[8]
In 2022, Filloux was appointed as the centre director of SCELSE in Singapore, where he continues to explore biofilm formation and bacterial secretion systems. His research on biofilms and bacterial virulence factors continues to shape the field of bacterial infection biology.
Filloux has held several scientific administrative positions including membership of the BBSRC - Research Grants Committee B (2009-2011),[11][12] the MRC Infection and immunity board (2016-2020), the FWO panel Medical Microbiology (2017-2023). He was also chair of the ANR scientific committee on microbiology, immunology and infection (2008-2011 and 2014-2018).
Bernal, P.; Furniss, R. C. D.; Fecht, S.; Leung, R. C. Y.; Spiga, L.; Mavridou, D. A. I.; Filloux, A. (2021-02-16). "A novel stabilization mechanism for the type VI secretion system sheath". Proceedings of the National Academy of Sciences of the United States of America. 118 (7): e2008500118. doi:10.1073/pnas.2008500118. PMID 33558227.
Hachani, A.; Wood, T. E.; Filloux, A. (2016-02). "Type VI secretion and anti-host effectors". Current Opinion in Microbiology. 29: 81–93. doi:10.1016/j.mib.2015.11.006. Epub 2015 Dec 24. PMID 26722980.
