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  Director : EL SOLH, Névine (nelsolh@pasteur.fr)



Staphylococci cause severe bacterial infections. Staphylococcal infections are highly prevalent among infectious diseases. They can be difficult to treat because hospital strains are multiresistant to antibiotics. The research activities associated with the National Reference Center attached to the unit are the identification and molecular typing of strains and analysis of resistance to antibiotics. Another research theme is the identification of cell wall factors responsible for adhesion to proteins of the extracellular matrix. This work will help elucidate the physiopathology of staphylococcal infections of prostheses.



Analysis of binding to matrix proteins of the central domain of Atl-type staphylococcal autolysins: J. Allignet, I. Old, N. El Solh, in collaboration with P. England

The two enzymatic domains of Atl-type autolysins are separated by three imperfected repeats which include GW dipeptides (glycin-tryptophan). The central domains of Atl (S. aureus), AtlE (S. epidermidis) and AtlC (S. caprae) have been purified. These domains bind to several matrix proteins: fibronectin, fibrinogen, vitronectin and bone sialoprotein. Surface plasmon resonance (BIAcore) was used to study the interaction of the repeat domain of AtlC with fibronectin. The kinectic curve reflects the existence of several type of interactions having distinct affinities (Kd = 10-9 M). Another approach based on phage-display was also used. M13 type phages expressing the pIIII surface protein fused to random heptapeptides were used. Thirteen of the 44 phages exhibiting strong and specific binding to AtlC R domain had an identical exposed peptide with similarity to vitronectin. Peptides exhibiting similarities with fibronectin were detected in the other phages. These similarities were taken into consideration for the choice of synthetic peptides which are presently tested to evaluate their capacity to inhibit binding of Atl-type autolysins to fibronectin or to vitronectin.

Characterization of the serine-aspartate (SD) staphylococcal proteins, SdrY, which includes a fibronectin binding domain: S. Aubert, J. Allignet, N. El Solh, in collaboration with Cécilia Rydèn

Proteins which include a domain rich in SD are putative adhesins. Two genes encoding SD proteins, sdrY and sdrZ, were isolated from an infectious S. caprae strain and sequenced. These two genes were found in all tested S. caprae strains. The sizes of the regions encoding SD domains differed between strains, suggesting that these regions are subject to rearrangements. A domain binding fibronectin was found in SdrY (1049 aa) which contains a LPDTG motif in the C-terminal part. None of the SdrZ domains bound to the matrix proteins tested (fibronectin, fibrinogen, vitronectin, and bone sialoprotein). SdrZ (539 aa) is similar to S. epidermidis SdrH and its C-terminal part is rich in hydrophobic amino acids but devoide of a LPXTG motif. SdrY is the first fibronectin-binding surface protein characterized among strains belonging to staphylococcal coagulase-negative species.

Analysis of the insertion sites, in the genome of S. aureus clinical isolates, of transposon Tn5406 conferring resistance to streptogramin A: J. Haroche, J. Allignet, N. El Solh

Tn5406 carries a variant of the vga(A) gene encoding an ABC protein which confers resistance to streptogramin A. The two genes involved in its transposition are similar to those of Tn554. One or two copies of Tn5406 have been detected in the chromosome and/or the plasmids of four tested S. aureus clinical isolates. The plasmids in which Tn5406 was inserted contained two other streptogramin A resistance genes, vga(B)-vat(B). The chromosomal copies were inserted either in the Tn554 preferential insertion site or in a site located in the mecIII-A type cassette. In both chromosomal sites, there are an interruption of genes encoding proteins similar to YsxA or RadC involved in DNA repair. Circular forms of Tn5406 were detectable in the cellular DNA of two of the four tested strains, suggesting that this transposon might be active.

Structure-function anlaysis of the Vga protein: O. Chesneau, N. El Solh

A transversal research program (PTR-55) has been launched (collaborations with Elie Dassa, Molecular Programmation and Genetic Toxicology Unit; Jean-Luc Guesdon, Antibodies Ingeeniering Laboratory; and Muriel Delepierre, Nuclear Magnetic Resonance of Biomolecules Unit) to study the molecular mechanism of functioning of a bi-domain ABC protein implicated in the resistance to streptogramin A antibiotic.

Activités du Centre National de Référence (CNR) des Staphylocoques (http://www.pasteur.fr/sante/cire/cadrecnr/staph-activites.html) N. El Solh, O. Chesneau, A. Morvan, S. Aubert (remplacée par M. Davi depuis08/01), J. Allignet

The activity of the National Reference Centre (CNR) concerns principally taxonomy, typing and antibiotic resistance. In 2000, 417 strains were analysed. A notable concern was the spread of epidemic clones of S. aureus resistant to ß-lactamins and with reduced sensitivity to glycopeptides. The CNR, upon the request of the "Institut de Veille Sanitaire" and the "Antibiogram Committee of the French Microbiological Society", participated in the evaluation of the importance of this phenomenon and of methods for the rapid screening of such strains in hospital microbiology laboratories.


puce Publications of the unit on Pasteur's references database


  Office staff Researchers Scientific trainees Other personnel

TRAN, Catherine - I.P. cathtran@pasteur.fr

EL SOLH, Névine - Chef d'Unité - I.P. nelsolh@pasteur.fr

CHESNEAU, Olivier - Assistant de recherche - I.P. - chesneau@pasteur.fr

OLD, Iain - Assistant de recherche - I.P. - igold@pasteur.fr

HAROCHE, Julien (thèse en sciences)

HOSAN-AGHAIE, Negin (depuis le 3/12/01)

ALLIGNET, Jeanine - Ingénieur Position II - I.P. allignet@pasteur.fr

MORVAN, Anne - Technicienne Supérieure de Laboratoire - I.P. amorvan@pasteur.fr

Jusqu'en août 01:

AUBERT, Sylvie - Technicienne Supérieure de Laboratoire - I.P.

Depuis août 01 :

DAVI, Marilyne - Technicienne Supérieure de Laboratoire - I.P. mdavi@pasteur.fr


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