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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:

 

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 Aug 11;
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 Jul 28;
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 1; 196(15):2775-88
PMID: 24837291

Ha DG, Kuchma SL, O'Toole GA
Plate-based assay for swarming motility in Pseudomonas aeruginosa.
Methods Mol Biol 2014; 1149:67-72
PMID: 24818898

Ha DG, Kuchma SL, O'Toole GA
Plate-based assay for swimming motility in Pseudomonas aeruginosa.
Methods Mol Biol 2014; 1149:59-65
PMID: 24818897

May RM, Hoffman MG, Sogo MJ, Parker AE, O'Toole GA, Brennan AB, Reddy ST
Micro-patterned surfaces reduce bacterial colonization and biofilm formation in vitro: Potential for enhancing endotracheal tube designs.
Clin Transl Med 2014; 3:8
PMID: 24739529

Ha DG, Richman ME, O'Toole GA
Deletion mutant library for investigation of functional outputs of cyclic diguanylate metabolism in Pseudomonas aeruginosa PA14.
Appl Environ Microbiol 2014 Jun; 80(11):3384-93
PMID: 24657857

El-Kirat-Chatel S, Beaussart A, Boyd CD, O'Toole GA, Dufrene YF
Single-cell and single-molecule analysis deciphers the localization, adhesion, and mechanics of the biofilm adhesin LapA.
ACS Chem Biol 2014 Feb 21; 9(2):485-94
PMID: 24556201

Lovewell RR, Hayes SM, O'Toole GA, Berwin B
Pseudomonas aeruginosa flagellar motility activates the phagocyte PI3K/Akt pathway to induce phagocytic engulfment.
Am J Physiol Lung Cell Mol Physiol 2014 Apr 1; 306(7):L698-707
PMID: 24487390