Alain Filloux

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Alain Ange-Marie Filloux
Professor Alain Filloux, January 2021.jpg
Born (1961-05-01) May 1, 1961 (age 61)
Alma mater Universite d'Aix-Marseille II
Scientific career
Fields
Institutions Utrecht University
French National Centre for Scientific Research
Imperial College London
Thesis Etude de la secrétion des protéines chez Pseudomonas aeruginosa  (1988)
Doctoral advisor Professor Andrée Lazdunski

Alain Ange-Marie Filloux (born May 1, 1961) is a French/British microbiologist who is a Professor of Molecular Microbiology at Imperial College London. [1] 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.

Contents

Early life and education

Filloux was a graduate student at Universite d'Aix-Marseille II, where he started to study protein secretion in Pseudomonas aeruginosa. [2] [3] 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. [4]

Research and career

In 1990, Filloux was promoted to Assistant Professor at Utrecht University, and continued to explore protein secretion in Gram-negative bacteria. [3] 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. [3] In particular he co-discovered what is now called the type II secretion system (T2SS). [3] This finding contributed to understanding protein secretion systems in Gram-negative bacteria, which are essential to their pathogenicity. [3]

In 1994, Filloux was appointed to the French National Centre for Scientific Research (CNRS) [4] 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. [4] 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. [5] 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. [6]

One such example is VgrG2b, which contains a metallopeptidase domain targeting, in the prey bacteria, proteins involved in cell wall integrity and cell division. [6] Bacterial preys will then collapse, as they do for example when treated with Βeta-lactam antibiotics. [6] 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. [6]

While continuing studying protein secretion and biofilm formation, Filloux gained interest investigating antibiotic resistance. [7] [8] He collaborated with Dr Gerald Larrouy-Maumus on the development of a protocol for rapid antibiotic resistance screening using mass spectrometry. [9]

Membership and editorial boards

Filloux has served as an editor for several scientific journals. [4] [10] Filloux was appointed Editor-in-Chief for FEMS Microbiology Reviews in 2013. [4] He was appointed Editor-in-Chief for npj Biolfilms and Microbiomes, which is part of the Nature Partner Journals series, in 2018. [10] [11]

Filloux has held several scientific administrative positions including membership of the BBSRC - Research Grants Committee B (2009-2011). [12] [13]

Awards and honours

Selected academic works

Publications

Books

Related Research Articles

<span class="mw-page-title-main">Biofilm</span> Aggregation of bacteria or cells on a surface

A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymeric substances (EPSs). The cells within the biofilm produce the EPS components, which are typically a polymeric conglomeration of extracellular polysaccharides, proteins, lipids and DNA. Because they have three-dimensional structure and represent a community lifestyle for microorganisms, they have been metaphorically described as "cities for microbes".

<i>Pseudomonas</i> Genus of Gram-negative bacteria

Pseudomonas is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a wide range of niches. Their ease of culture in vitro and availability of an increasing number of Pseudomonas strain genome sequences has made the genus an excellent focus for scientific research; the best studied species include P. aeruginosa in its role as an opportunistic human pathogen, the plant pathogen P. syringae, the soil bacterium P. putida, and the plant growth-promoting P. fluorescens, P. lini, P. migulae, and P. graminis.

<span class="mw-page-title-main">Secretion</span> Controlled release of substances by cells or tissues

Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mechanism of cell secretion is via secretory portals at the plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structures embedded in the cell membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.

<span class="mw-page-title-main">Phage therapy</span> Therapeutic use of bacteriophages to treat bacterial infections

Phage therapy, viral phage therapy, or phagotherapy is the therapeutic use of bacteriophages for the treatment of pathogenic bacterial infections. This therapeutic approach emerged at the beginning of the 20th century but was progressively replaced by the use of antibiotics in most parts of the world after the Second World War. Bacteriophages, known as phages, are a form of virus that attach to bacterial cells and inject their genome into the cell. The bacteria's production of the viral genome interferes with its ability to function, halting the bacterial infection. The bacterial cell causing the infection is unable to reproduce and instead produces additional phages. Phages are very selective in the strains of bacteria they are effective against.

<i>Pseudomonas aeruginosa</i> Species of bacterium

Pseudomonas aeruginosa is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes.

<span class="mw-page-title-main">Filamentation</span>

Filamentation is the anomalous growth of certain bacteria, such as Escherichia coli, in which cells continue to elongate but do not divide. The cells that result from elongation without division have multiple chromosomal copies.

<span class="mw-page-title-main">Cyclic di-GMP</span> Chemical compound

Cyclic di-GMP is a second messenger used in signal transduction in a wide variety of bacteria. Cyclic di-GMP is not known to be used by archaea, and has only been observed in eukaryotes in Dictyostelium. The biological role of cyclic di-GMP was first uncovered when it was identified as an allosteric activator of a cellulose synthase found in Gluconacetobacter xylinus in order to produce microbial cellulose.

Roberto Kolter is Professor of Microbiology, Emeritus at Harvard Medical School, an author, and past president of the American Society for Microbiology. Kolter has been a professor at Harvard Medical School since 1983 and was Co-director of Harvard's Microbial Sciences Initiative from 2003-2018. During the 35-year term of the Kolter laboratory from 1983 to 2018, more than 130 graduate student and postdoctoral trainees explored an eclectic mix of topics gravitating around the study of microbes. Kolter is a fellow of the American Association for the Advancement of Science and of the American Academy of Microbiology.

<span class="mw-page-title-main">Pseudomon-1 RNA motif</span>

The Pseudomon-1 RNA motif is a conserved RNA identified by bioinformatics. It is used by most species whose genomes have been sequenced and that are classified within the genus Pseudomonas, and is also present in Azotobacter vinelandii, a closely related species. It is presumed to function as a non-coding RNA. Pseudomon-1 RNAs consistently have a downstream rho-independent transcription terminator.

Bacterial small RNAs (bsRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.

Bacterial morphological plasticity refers to changes in the shape and size that bacterial cells undergo when they encounter stressful environments. Although bacteria have evolved complex molecular strategies to maintain their shape, many are able to alter their shape as a survival strategy in response to protist predators, antibiotics, the immune response, and other threats.

<span class="mw-page-title-main">Urs Jenal</span>

Urs Jenal is a Swiss Microbiologist and Professor at the Biozentrum University of Basel, Switzerland.

The type VI secretion system (T6SS) is molecular machine used by a wide range of Gram-negative bacterial species to transport effectors from the interior of a bacterial cell across the cellular envelope into an adjacent target cell. While often reported that the T6SS was discovered in 2006 by researchers studying the causative agent of cholera, Vibrio cholerae, the first study demonstrating that T6SS genes encode a protein export apparatus was actually published in 2004, in a study of protein secretion by the fish pathogen Edwardsiella tarda.

<span class="mw-page-title-main">Twitching motility</span> Form of crawling bacterial motility

Twitching motility is a form of crawling bacterial motility used to move over surfaces. Twitching is mediated by the activity of hair-like filaments called type IV pili which extend from the cell's exterior, bind to surrounding solid substrates and retract, pulling the cell forwards in a manner similar to the action of a grappling hook. The name twitching motility is derived from the characteristic jerky and irregular motions of individual cells when viewed under the microscope. It has been observed in many bacterial species, but is most well studied in Pseudomonas aeruginosa, Neisseria gonorrhoeae and Myxococcus xanthus. Active movement mediated by the twitching system has been shown to be an important component of the pathogenic mechanisms of several species.

<span class="mw-page-title-main">Bacterial secretion system</span> Protein complexes present on the cell membranes of bacteria for secretion of substances

Bacterial secretion systems are protein complexes present on the cell membranes of bacteria for secretion of substances. Specifically, they are the cellular devices used by pathogenic bacteria to secrete their virulence factors to invade the host cells. They can be classified into different types based on their specific structure, composition and activity. Generally, proteins can be secreted through two different processes. One process is a one-step mechanism in which proteins from the cytoplasm of bacteria are transported and delivered directly through the cell membrane into the host cell. Another involves a two-step activity in which the proteins are first transported out of the inner cell membrane, then deposited in the periplasm, and finally through the outer cell membrane into the host cell.

<span class="mw-page-title-main">Katharina Ribbeck</span> German-American biochemist and biophysicist

Katharina Ribbeck is a German-American biologist. She is the Andrew (1956) and Erna Viterbi Professor of Biological Engineering at the Masschusetts Institute of Technology. She is known as one of the first researchers to study how mucus impacts microbial behavior. Ribbeck investigates both the function of mucus as a barrier to pathogens such as fungi, bacteria, and viruses and how mucus can be leveraged for therapeutic purposes. She has also studied changes that cervical mucus undergoes before birth, which may lead to a novel diagnostic for the risk of preterm birth.

Karine Gibbs is a Jamaican American microbiologist and immunologist and an associate professor in the Department of Plant and Microbial Biology at the University of California, Berkeley. Gibbs’ research merges the fields of sociomicrobiology and bacterial cell biology to explore how the bacterial pathogen Proteus mirabilis, a common gut bacterium which can become pathogenic and cause urinary tract infections, identifies self versus non-self. In 2013, Gibbs and her team were the first to sequence the genome of P. mirabilis BB2000, the model organism for studying self-recognition. In graduate school at Stanford University, Gibbs helped to pioneer the design of a novel tool that allowed for visualization of the movement of bacterial membrane proteins in real time. In 2020, Gibbs was recognized by Cell Press as one of the top 100 Inspiring Black Scientists in America.

Kalai Mathee is a professor at Florida International University, joint editor-in-chief of the Journal of Medical Microbiology, and an elected fellow of the American Academy of Microbiology. She is known for her research on bacterial infections caused by Pseudomonas aeruginosa.

Niels Høiby is a Danish physician, professor and politician. He specialises in microbiology and was a pioneer in the study of biofilms and their role in conditions such as cystic fibrosis. He worked for many years as a department head at Denmark's largest hospital, the Rigshospitalet.

Garth David Ehrlich is a molecular biologist, genomic scientist, academic, and author who is most known for his development of the distributed genome hypothesis and bringing the biofilm paradigm to the field of chronic mucosal bacterial diseases. He is a Professor of Microbiology and Immunology, and Otolaryngology-Head and Neck Surgery at Drexel University. He is also the founder and executive director of three Research Centers of Excellence: the Center for Genomic Sciences (CGS); the Center for Advanced Microbial Processing (CAMP); and the Center for Surgical Infections and Biofilms. In addition, he serves as the executive director of the Genomics Core Facility and the director of Molecular Pathology within Drexel Medicine Diagnostics and the Sidney Kimmel Cancer Center's Meta-omics Core Facility.

References

  1. "Alain Filloux". scholar.google.com. Retrieved 2021-06-23.
  2. Filloux, Alain (1988). Etude de la secrétion des protéines chez Pseudomonas aeruginosa (Thesis) (in French). OCLC   1164072817.
  3. 1 2 3 4 5 6 "Filloux". Fondation Bettencourt Schueller (in French). 2014-09-30. Retrieved 2021-01-05.
  4. 1 2 3 4 5 6 "FEMS Expert: Professor Alain Filloux". FEMS. Retrieved 2021-01-05.
  5. "Professor Alain Filloux". Imperial College London. Retrieved 2021-01-05.
  6. 1 2 3 4 "'Poisoned arrowhead' used by warring bacteria could lead to new antibiotics | Imperial News | Imperial College London". Imperial News. Retrieved 2021-01-05.
  7. "A toxic bullet involved in bacterial competition found by researchers | Imperial News | Imperial College London". Imperial News. Retrieved 2021-01-05.
  8. "A toxic bullet involved in bacterial competition". ScienceDaily. Retrieved 2021-01-05.
  9. "New test can identify dangerous bacteria resistant to last-resort antibiotic | Imperial News | Imperial College London". Imperial News. Retrieved 2021-01-05.
  10. 1 2 "About the Editors | npj Biofilms and Microbiomes". www.nature.com. Retrieved 2021-06-24.
  11. Community, Nature Portfolio Microbiology (2020-03-26). "Happy Birthday npj Biofilms and Microbiomes!". Nature Portfolio Microbiology Community. Retrieved 2021-06-24.
  12. "2010-2011 Annual Report and Account - BBSRC" (PDF). assets.publishing.service.gov.uk. 28 February 2012. Archived (PDF) from the original on 2019-07-25. Retrieved 24 June 2021.
  13. "Annual Report and Accounts 2009-2010 - BBSRC" (PDF). assets.publishing.service.gov.uk. 4 April 2011. Archived (PDF) from the original on 2019-07-24. Retrieved 24 June 2021.
  14. 1 2 "Honours and Memberships - Professor Alain Filloux". www.imperial.ac.uk. Retrieved 2021-01-05.
  15. "rae 2008 : submissions : ra5a". www.rae.ac.uk. Retrieved 2021-01-05.
  16. "Alain Filloux elected to European Academy of Microbiology | Imperial News | Imperial College London". Imperial News. Retrieved 2021-06-23.
  17. "Alain Filloux elected to Fellowship of the American Academy of Microbiology | Imperial News | Imperial College London". Imperial News. Retrieved 2021-06-23.