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George A. O'Toole, Ph.D.

Title(s):
Professor of Microbiology and Immunology

Department(s):
Microbiology and Immunology

Education:
University of Wisconsin - Madison, Ph.D., 1994
Cornell University, B.S., 1988

After postdoctoral work at the University of Wisconsin-Madison and Harvard Medical School, Dr. O'Toole joined the faculty of the Department of Microbiology at Dartmouth Medical School in 1999

Programs:
Immunology Program
Molecular and Cellular Biology Graduate Programs
Molecular Pathogenesis Program

Websites:
http://dms.dartmouth.edu/microbio/
http://www.dartmouth.edu/~molpath/
http://dms.dartmouth.edu/mcb/
http://www.dartmouth.edu/~gotoole/

Contact Information:

Dartmouth Medical School
Vail Building - HB 7550
Hanover NH 03755

Phone: 603-650-1248
Fax: 603-650-1318
Email: George.A.Otoole@Dartmouth.Edu


Professional Interests:

The main focus of the O’Toole laboratory is the study of complex surface-attached bacterial communities known as biofilms. Biofilms can form on a wide variety of surfaces including catheter lines, surgical implants, contact lenses, the lungs of patients with cystic fibrosis, industrial and drinking water pipelines, and on the surfaces of plant roots. In most natural, clinical, and industrial settings bacteria live predominantly in biofilms and not as planktonic (free-swimming) cells such as those typically studied in the laboratory. Bacteria growing in biofilm communities are of great interest to the medical community, because these bacteria become highly resistant to antibiotics by an as yet unknown mechanism. Although much has been learned about the types of microbes that can form biofilms, the morphology of these communities, and their chemical/physical properties, until recently little was known about the molecular genetic basis of biofilm formation or antibiotic resistance.

Studies in the O’Toole lab focus on:
• The molecular genetic basis of biofilm formation.
• The role of the intracellular signaling molecule c-di-GMP in controlling biofilm formation by pseudomonads.
• The signal transduction pathways regulating biofilm formation.
• The mechanisms by which biofilms form on biotic, or living surfaces, and why these biofilms are so highly resistant to antibiotics. We have developed a novel model system for studying biofilms on airway epithelial cells, and these studies are done, in particular, in the context of cystic fibrosis.
• The role of lysogenic phages in impacting biofilm formation.

Recent collaborative studies with Dr. Bruce Stanton’s group here at Dartmouth have explored questions of host-pathogen interactions, using the interplay between the bacterial pathogen Pseudomonas aeruginosa and airway epithelial cells as a model system. We are particularly interested in the role of the toxin, Cif, in altering epithelial cell biology and protein trafficking. We are also studying mechanisms by which P. aeruginosa delivers toxins to host cells.

Please visit the O'Toole Lab Home Page.


Selected Publications:

 

Willger SD, Grim SL, Dolben EL, Shipunova A, Hampton TH, Morrison HG, Filkins LM, O'Toole GA, Moulton LA, Ashare A, Sogin ML, Hogan DA
Characterization and quantification of the fungal microbiome in serial samples from individuals with cystic fibrosis.
Microbiome 2014; 2:40
PMID: 25408892

Siryaporn A, Kuchma SL, O'Toole GA, Gitai Z
Surface attachment induces Pseudomonas aeruginosa virulence.
Proc Natl Acad Sci U S A 2014 Nov 25; 111(47):16860-5
PMID: 25385640

Kuchma SL, Delalez NJ, Filkins LM, Snavely EA, Armitage JP, O'Toole GA
c-di-GMP-Mediated Repression of Swarming Motility by Pseudomonas aeruginosa PA14 requires the MotAB Stator.
J Bacteriol 2014 Oct 27;
PMID: 25349157

Chen AI, Dolben EF, Okegbe C, Harty CE, Golub Y, Thao S, Ha DG, Willger SD, O'Toole GA, Harwood CS, Dietrich LE, Hogan DA
Candida albicans ethanol stimulates Pseudomonas aeruginosa WspR-controlled biofilm formation as part of a cyclic relationship involving phenazines.
PLoS Pathog 2014 Oct; 10(10):e1004480
PMID: 25340349

Beaussart A, Baker AE, Kuchma SL, El-Kirat-Chatel S, O'Toole GA, Dufrene YF
Nanoscale adhesion forces of Pseudomonas aeruginosa type IV Pili.
ACS Nano 2014 Oct 28; 8(10):10723-33
PMID: 25286300

Chatterjee D, Cooley RB, Boyd CD, Mehl RA, O'Toole GA, Sondermann H
Mechanistic insight into the conserved allosteric regulation of periplasmic proteolysis by the signaling molecule cyclic-di-GMP.
Elife 2014 Sep 2; 3:e03650
PMID: 25182848

Ballok AE, Filkins LM, Bomberger JM, Stanton BA, O'Toole GA
Epoxide-mediated differential packaging of Cif and other virulence factors into outer membrane vesicles.
J Bacteriol 2014 Oct; 196(20):3633-42
PMID: 25112474

Hampton TH, Green DM, Cutting GR, Morrison HG, Sogin ML, Gifford AH, Stanton BA, O'Toole GA
The microbiome in pediatric cystic fibrosis patients: the role of shared environment suggests a window of intervention.
Microbiome 2014; 2:14
PMID: 25071935

Celaj S, Gleeson MW, Deng J, O'Toole GA, Hampton TH, Toft MF, Morrison HG, Sogin ML, Putra J, Suriawinata AA, Gorham JD
The microbiota regulates susceptibility to Fas-mediated acute hepatic injury.
Lab Invest 2014 Sep; 94(9):938-49
PMID: 25068658

Boyd CD, Smith TJ, El-Kirat-Chatel S, Newell PD, Dufrene YF, O'Toole GA
Structural features of the Pseudomonas fluorescens biofilm adhesin LapA required for LapG-dependent cleavage, biofilm formation, and cell surface localization.
J Bacteriol 2014 Aug; 196(15):2775-88
PMID: 24837291