Research Laboratories

Research Team EA 2656


Rouen Normandie University, Ministry of Education and Research
Research group on antimicrobial agents and microorganisms
GRAM

Head


Pr François Caron

Secretary: Stéphanie Legris

Contact


GRAM
Faculté de Médecine et de Pharmacie
22 Boulevard Gambetta
76183 Rouen Cedex
Phone: +33 235 14 8452
francois.caron@chu-rouen.fr
stephanie.legris@univ-rouen.fr

Research Topics


  • Genetic diversity of HIV and antiretroviral agents
  • Bacterial cell wall dynamics and bactericidal activity
  • Emerging antimicrobial resistance and infectious diseases

Composition


  • 6 teacher-researchers and 4 hospital practitioners (PhD)
  • 1 engineer
  • 7 PhD students

Facilities


  • BSL-3
  • Laboratory associated with the National Reference Center for HIV
  • Laboratory collaborating with the National Reference Center for anaerobes (Clostridium difficile)
  • Viral genome sequencing. Elisa technology and platform. Cloning and expression of bacterial proteins. Site-directed mutagenesis.
  • In vitro and animal models of infection

Activity


This unit gathers microbiologists, and infectious disease specialists from the University of Rouen. The group is conducting research both in vitro, in animal models of experimental infection, and humans.
Microbial resistance, selected by therapies or aided by the natural genetic diversity, is a major public health problem and led the research group to develop three themes:
- The virological team focuses its activity on the genetic diversity of HIV and its consequences, by studying the impact of the genetic diversity of rare variants of HIV-1 group O and the new group P (discovered by the group) on antiretrovirals agents susceptibility in vitro and in vivo, and by studying the genetic and phenotypic evolution of HIV-1 group O by recombination with pandemic viruses of HIV-1 group M.
- The bacteriological team studies the functions of autolysins of  Staphylococcus lugdunensis and Clostridium difficile in term of bacterial growth (role in cell division), virulence (adherence to host cells and foreign devices, production of biofilm, pro-inflammatory effect of the peptidoglycan cleavage products), and bactericidal activity (tolerance to cell-wall-active antibiotics).
- The clinician team develops studies on urinary tract infections difficult-to-treat because of anatomic localization (prostatitis), presence of a catheter (that promotes biofilm formation) or multi-drug resistance. The team also works on emerging infectious diseases (regional outbreak of invasive meningococcal infections).
For all these studies, the unit has developed many national and international cooperations (particularly with the French National Reference Centers dedicated to the infectious agents studied).

Main Contributions


  • Development of molecular tools for the detection and analysis of dual infections HIV-1 M + HIV-O and associated recombinants forms.
  • Development of molecular techniques for complete genome characterization, study of viral quasi-species, and of phenotypic tools for analysis of the virologic properties of HIV-1 groups O and P variants.
  • Study of the involvement of autolysins of Staphylococcus lugdunensis and Clostridium difficile and their regulation systems in bacterial growth, virulence (adhesion properties of autolysins) and bactericidal activity or tolerance to antibiotics.
  • Development of a rabbit model of catheter associated urinary tract infection that allow to explore in vivo the mechanisms of bacterial persistence in biofilm.
  • Contribution to the investigation and the control of a Neisseria meningitidis outbreak.

Main Publications


2014

  • Etienne M, Lefebvre E, Frebourg N, Hamel H, Pestel-Caron M and Caron F; Bacyst Study Group. Antibiotic treatment of acute uncomplicated cystitis based on rapid urine test and local epidemiology: lessons from a primary care series. BMC Infect Dis 2014, 14: 137.
    24612927
  • Gibert L, Didi J, Marlinghaus L, Lesouhaitier O, Legris S, Szabados F, Pons JL and Pestel-Caron M. The major autolysin of Staphylococcus lugdunensis, AtlL, is involved in cell separation, stress-induced autolysis and contributes to bacterial pathogenesis. FEMS Microbiol Lett 2014, 352: 78-86.
    24393327

2013

  • Delbos V1, Lemée L, Bénichou J, Berthelot G, Deghmane AE, Leroy JP, Houivet E, Hong E, Taha MK and Caron F; B14 STOP study group. Impact of MenBvac, an outer membrane vesicle (OMV) vaccine, on the meningococcal carriage. Vaccine 2013, 31: 4416-20.
    23856330
  • El Meouche I1, Peltier J1, Monot M2, Soutourina O3, Pestel-Caron M1, Dupuy B2 and Pons JL4. Characterization of the SigD regulon of C. difficile and its positive control of toxin production through the regulation of tcdR. PLoS One 2013, 8: e83748.
    24358307
  • Leoz M1, Feyertag F, Charpentier C, Delaugerre C, Wirden M, Lemee V and Plantier JC. Characterization of CRF56_cpx, a new circulating B/CRF02/G recombinant form identified in MSM in France. AIDS 2013, 27: 2309-12.
    24157908
  • Mourez T1, Simon F and Plantier JC. Non-M variants of human immunodeficiency virus type 1. Clin Microbiol Rev 2013, 26: 448-61.
    23824367

2012

  • Caron F, Delbos V, Houivet E, Deghmane AE, Leroy JP, Hong E, Bénichou J and Taha MK. Evolution of immune response against Neisseria meningitidis B:14:P1.7,16 before and after the outer membrane vesicle vaccine MenBvac. Vaccine 2012, 30: 5059-62.
    22658929
  • Chassain B, Lemée L, Didi J, Thiberge JM, Brisse S, Pons JL and Pestel-Caron M. Multilocus sequence typing analysis of Staphylococcus lugdunensis implies a clonal population structure. J Clin Microbiol 2012, 50: 3003-9.
    22785196

2011

  • Caron F, du Châtelet IP, Leroy JP, Ruckly C, Blanchard M, Bohic N, Massy N, Morer I, Floret D, Delbos V, Hong E, Révillion M, Berthelot G, Lemée L, Deghmane AE, Bénichou J, Lévy-Bruhl D and Taha MK. From tailor-made to ready-to-wear meningococcal B vaccines: longitudinal study of a clonal meningococcal B outbreak. Lancet Infect Dis 2011, 11: 455-63.
    21489881
  • Delaugerre C, De Oliveira F, Lascoux-Combe C, Plantier JC and Simon F. HIV-1 group N: travelling beyond Cameroon. Lancet 2011, 378: 1894.
    22118443