Marc G.J. Feuilloley, Ph.D.

I got a double scientific experience in human physiology and microbiology that was at the origin of my interest to host-bacteria communication. The topic on “Cellular Microbiology” I developed in the LMDF-SME at my arrival was taking increasing importance, and I was proposed as director of LMSF-SME for a first period (2008-2011). In 2012, I started a second period as director, and my laboratory acquired its present name of “Laboratory of Microbiology Signals and Microenvironment (LMSM, EA4312)”. LMSM was noted A by the French evaluation agency AERES. In 2016, I was heading LMSM for a third period as director and another evaluation with excellent results over the 6 points considered by HCERES (3 notes A, 2 A+ and 1 A++ for society and economic impact). A great achievement in this period, under official mission by the University of Rouen and county of Eure, was the creation in 2016 of a building for research in microbiology, designated as Normandy Sanitary Safety Center (CSSN). The project, was granted for a total of 8.3 M€ plus 320 k€ of initial equipment, including 3.5 M€ from UE-FEDER). I have the scientific management of this building which harbour LMSM and 3 other partners: the technological platform Normandy Sanitary Safety (N2S), an association for food industry (PRAXENS) and a consortium (PFI Cosmetomics@Normandy) working with cosmetic industry. I am also involved in the management of these structures, particularly as member of the direction board and administrator of N2S. Because of my network with industry, from 2007 to 2017 I have been administrator and secretary of the Technopôle Chimie-Biologie-Santé (CBS) (Region Normandy). Since 2017, I am administrator of the cluster PolePharma gathering pharmaceutical industries representing the first production area for pharmaceuticals in Europe. I have been involved in projects headed by the world cluster for cosmetic industry Cosmetic Valley since its creation. I also act as expert form different companies (BioGalenys, LPS Bioscience, Uriage dermatological laboratories, Biomerieux). For those reasons, since 2011 I had was heading different projects labelled by the cluster Cosmetic Valley and granted by the French Ministry of Industry and UE-FEDER (FUI Virtual Skin Sensitization 2007-11: 498 k€ - FUI Skin O Flor 2009-12: 793 k€ - FUI Beta Clear 2011-14: 538 k€ - FUI Emulskin 2014-18:492 k€ - FUI Gynceutics 2017-21:204 k€ - PSPC-PIA4 MICCA 2020-23: 360 k€). I was also head for regional projects (RIN RNAmb and RIN LEGO: 392 948 € and 503 000 €) and UE-FEDER projects (Alternative toxicology: 466 k€ - COS SéSa: 871 k€). In parallel I developed be-to-be partnerships with industrial partners (486 k€ since 2015).

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I am Director of the LMSM, and will transfer the direction of this laboratory in 2022. In 2022 our group, that includes presently 18 permanent academic investigators will fuse with a research unit of Caen Normandy University (U2RM, EA4655) and give birth to the largest microbiology laboratory in Normandy designated as “Laboratory of Microbiology Bacterial Communication and Anti-Infection Strategies (LM-CBSA)” (37 permanent members). In this large unit, I will have the responsibility of the research axis “Communication in the human microbiota”. Indeed, although I exerted scientific and administrative functions (including as member of the French National Council of Universities (CNU) and as administrator of the Rouen Normandy University), and had complete teaching service (192 h/year), I always had an important scientific activity. Since 2011, I was author or co-author of 110 articles and 4 abstracts in peered reviewed journals, 6 articles and 13 reviews in journals not listed in international data bases, 10 book chapters and 2 patents (1 french and 1 international). Over the same period, I was invited to give 38 conferences in national and international symposia (including Netherland, Austria, Poland, Russia, Canada and Korea) and was invited lecturer at the International Max Plank Research School (IMPRS, Germany). I was author and co-author of 83 oral presentations in national and international congress and 177 poster presentations. In was also coordinator of 2 books and gest editor for a review. In was also organizer and co-organizer of 14 national scientific symposia. I was recipient of the price of the French Society of Microbiology SFM (2014) and International Federation of Societies of Cosmetic Chemists IFSCC (2014). My present H index (ResearchGate) is 43.24.

Since 2009, I started to investigate the interaction of cutaneous bacteria with skin. Indeed, skin is the largest neuroimmunoendocrine organ of the human body and almost all neurotransmitters, neurohormones and hormones are produced or released in skin. One quarter of the cutaneous microbiota is installed deeply into the skin and cutaneous bacteria are directly exposed to these local factors. In a first study, I focused on the potential impact of Substance P (SP, the more abundant skin neuropeptide) on bacterial virulence in the context of the sensitive skin syndrome. I showed that SP can specifically stimulate the virulence and/or biofilm formation activity of Gram-positive and Gram negative cutaneous bacterial strains [1, 2]. The sensor, was identified as the thermo unstable ribosomal elongation factor EfTu. This protein is classically involved in the transfer of aminoacylated tRNA to the ribosome, but I showed that EfTu, can be exported through the membrane by MscL large mechanosensitive channels and that SP promotes the association of EfTu to the membrane before leading to the bacterial response [3]. This behaviour is typical of moonlighting proteins, a special class of multifunctional proteins having different functions in the bacteria stroma and in the membrane. In skin, SP is often released in association to the Calcitonin Gene Related Peptide (CGRP) by nerves terminals. I showed that CGRP can also stimulate S. epidermidis virulence but its mechanism of action is different and its sensor was identified as DnaK, a protein of the Hsp70 family which is also a moonlighting protein [4]. Its mechanism of action is now investigated in an ANR project under the responsibility of my collaborators. SP and CGRP are essential components of cutaneous neurogenic inflammation. The third family of neuropeptide involved in this process, natriuretic peptides (ANP and CNP), was investigated in the framework of a PhD I headed in co-direction with Moscow university. We showed that ANP and CNP are modulating the competitiveness of S. aureus in regard of S. epidermidis [5]. Natriuretic peptides can also module the virulence and biofilm formation activity of Pseudomonas, and this discovery was leading to a world patent [6]. Skin is also rich in in sympathetic nerve endings and I showed that catecholamines potentiate Cutibacterium acnes induced sebocytes lipogenesis, suggesting that this bacterium should be a relay between stress and acne [7]. A sensor, the KdpD protein, was suggested from bioinformatics and molecular docking studies. More recently, I initiated a study on the effect of steroid hormones on bacteria. This was investigated in the context of the vaginal mucosa by looking at the impact of 17β estradiol on the physiology of lactobacilles and I demonstrated that 17β-estradiol modulates biosurfactant production and adhesion of Lactobacillus crispatus to vaginal cells[8].

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These studies were leading to revise the mechanism of cutaneous neurogenic inflammation by inserting in the pathway the role of the skin microbiota [9], and to promote the concept of “Cutaneous bacterial endocrinology”[10]. As considered by the French research evaluation committee HCERES and industrial partners, my lab and myself are presently leaders in the field of skin-bacteria communication.

References

1. Mijouin L, Hillion M, Ramdani Y, Jaouen T, Duclairoir-Poc C, Follet-Gueye M-L, Lati E, Yvergnaux F, Driouich A, Lefeuvre L, Farmer C, Misery L, Feuilloley M.G.J. (2013) Effects of a neuropeptide (substance P) on cutaneous microflora. PLoS One 8: e78773. doi:10.1371/journal.pone.0078773

2. N’Diaye A, Mijouin L, Hillion M, Diaz S, Konto-Ghiorghi Y, Percoco G, Chevalier S, Lefeuvre L, Harmer N.J, Lesouhaitier O, Feuilloley M.G.J. (2016) Effect of Substance P in Staphylococcus aureus and Staphylococcus epidermidis virulence: Implication for skin homeostasis. Front. Microbiol. 7: 1-15, Art 506. doi: 10.3389/fmicb.2016.00506

3. N'Diaye A.R, Borrel V, Racine P-J, Clamens T, Depayras S, Maillot O, Schaack B, Chevalier S, Lesouhaitier O, Feuilloley M.G.J. (2019) Mechanism of action of the moonlighting protein EfTu as a Substance P sensor in Bacillus cereus. Sci. Rep. 9: 1304. doi: 10.1038/s41598-018-37506-6

4. N’Diaye A.R, Leclerc C, Kentache T, Hardouin J, Duclairoir Poc C, Konto-Ghiorghi Y, Chevalier S, Lesouhaitier O, Feuilloley M.G.J. (2016) Skin - bacteria communication: Involvement of the neurohormone Calcitonin Gene Related Peptide (CGRP) in the regulation of Staphylococcus epidermidis virulence. Sci. Rep. 6: 35379. doi: 10.1038/srep35379

5. Gannesen AV, Lesouhaitier O, Netrusov AI, Plakunov VK, Feuilloley M.G.J. (2018) The new role of human natriuretic peptides: regulation of monospecies and binary biofilms formation of skin Staphylococcus epidermidis and Staphylococcus aureus. Microbiology 87: 597-609. doi:10.1134/S0026261718050090

6. Lesouhaitier O, Feuilloley M, Clamens T, Rodrigues S, Laurency S, Louis M. (2021) Osteocrin, lebetin or and ANP for destroying bacterial biofilms. 04/02/2021. World patent WO2021/018792

7. Borrel V, Thomas P, Catovic C, Racine P-J, Konto-Ghiorghi Y, Lefeuvre L, Duclairoir-Poc C, Zouboulis C.C, Feuilloley M.G.J. (2019) Acne and stress: Impact of catecholamines on Cutibacterium acnes. Front. Med., 6: 155. doi: 10.3389/fmed.2019.00155

8. Clabaut M, Boukerb A, Mlouka A.B, Suet A, Tahrioui A, Verdon J, Barreau M, Maillot O, Le Tirant A, Karsybayeva M, Kremser C, Redziniak G, Duclairoir-Poc C, Pichon C, Hardouin J, Cosette P, Chevalier S, Feuilloley M.G.J. (2021) Variability of human vaginal Lactobacillus crispatus response to 17β-estradiol. Sci. Rep. 11: 11533. doi: 10.1038/s41598-021-91017-5

9. Feuilloley M.G.J. (2018) Antidromic neurogenic activity and cutaneous bacterial flora. Sem. Immunopathol. 40: 281-289 doi: 10.1007/s00281-018-0671-3

10. Racine P-J, Janvier X, Clabaut M, Catovic C, Souak D, Boukerb A.M, Groboillot A, Konto-Ghiorghi Y, Duclairoir-Poc C., Lesouhaitier O, Orange N, Chevalier S, Feuilloley M.G.J. (2020) Dialog between skin and its microbiota: Emergence of “Cutaneous Bacterial Endocrinology”. Exp. Dermato. 29: 1-11. doi : 10.1111/exd.14158