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Regulation of Staphylococcus aureus biofilm development studied by genome-wide expression analysis

English title Regulation of Staphylococcus aureus biofilm development studied by genome-wide expression analysis
Applicant Schrenzel Jacques
Number 103002
Funding scheme SNSF Professorships
Research institution Service des Maladies Infectieuses Département de Médecine Interne Hôpital Cantonal - HUG
Institution of higher education University of Geneva - GE
Main discipline Infectious Diseases
Start/End 01.05.2004 - 30.04.2006
Approved amount 483'042.00
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All Disciplines (2)

Discipline
Infectious Diseases
Experimental Microbiology

Keywords (10)

STAPHYLOCOCCUS AUREUS; CHRONIC INFECTIONS; MRNA MESSENGER PROFILING; BIOFILMS; HOST-PATHOGEN INTERACTION; MICROARRAYS; host-pathogen interactions; foreign-body infections; drug resistance; functional genomics

Lay Summary (English)

Lead
Lay summary
Microbial biofilms represent an important determinant of human chronicinfections(1). Bacterial biofilms involve a genetically-coordinatedsequence of events(2), including initial surface attachment, microcolonyformation and community expansion (3). This leads to a complex andstructured architecture protecting bacteria from host-defensemechanisms(4) and killing by antimicrobials(5-7). Among the mostclinically significant bacterial pathogens is Staphylococcus aureus, aleading cause of bone and foreign body infections(8-13). Despite highincidence and significant morbidity, the molecular pathogenesis of chronicstaphylococcal infections and contribution of biofilm production remainlargely unknown. This project will continue the study of geneticregulation of biofilm development using genome-wide S. aureus microarrayprofiling that has been recently implemented in our laboratory(www.genomic.ch).During this grant extension, we will: (i) perform a morphological analysisof biofilm development using confocal microscopy of fluorescently-labeledS. aureus, (ii) correlate morphologic stages with defined patterns of geneexpression, (iii) confirm the role of candidate genes essential forbiofilm formation by genetic screening of a random insertionalinactivation library, and (iv) genetically validate the most promisingtargets by standard inactivation and complementation strategies.Improved knowledge of the genetic basis of bacterial biofilms should leadto novel screening assays, identification of new drug targets, anddevelopment of advanced biomedical devices to prevent biofilm formation.Reference List1. Stickler,D. Biofilms. Curr. Opin. Microbiol. 2, 270-275 (1999).2. Costerton,J.W., Stewart,P.S. & Greenberg,E.P. Science 284, 1318-1322(1999).3. Mack,D. et al. Infect Immun. 62, 3244-3253 (1994).4. Zimmerli,W., Lew,P.D. & Waldvogel,F.A. J. Clni. Invest 73, 1191-1200(1984).5. Domingue,G., Ellis,B., Dasgupta,M. & Costerton,J.W. J. Clin.Microbiol. 32, 2564-2568 (1994).6. Darouiche,R.O. et al. J. Infect. Dis. 170, 720-723 (1994).7. Gilbert,P., Das,J. & Foley,I. Adv Denta. Res. 11, 160-167 (1997).8. Francois,P., Vaudaux,P. & Lew,P.D. Annals Vasc. Surg 12, 34-40(1998).9. Francois,P., Vaudaux,P., Foster,T.J. & Lew,D.P. Infect Contro Hosp.Epid. 17, 514-520 (1996).10. Gristina,A.G., Hobgood,C.D. & Barth,E. Pathogenesis and ClinicalSignificance of Coagulase-Negative Staphylococci. Pulverer,G., Quie,P.G. &Peters,G. (eds.), pp. 143-157 (1987).11. Wadstrom,T. Zentralblatt Bakt. Mikrob Hyg, 266, 191-211 (1987).12. Watanakunakorn,C. Clin Infect. Dis. 28, 115-116 (1999).13. Lew,D.P. & Waldvogel,F.A. New Engl J. Med 336, 999-1007 (1997).
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
57950 Genomic messengers of virulence and persistance: mRNA and protein profiling of Staphylococcus aureus biofilms during experimental chronic infection 01.05.2000 SNSF Professorships
112370 Kinetic analysis of S.aureus biofilm regulation by using combined imaging and genome-wide approaches 01.05.2006 Project funding (Div. I-III)

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