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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:

 

Ha DG, Richman ME, O'Toole GA
A deletion mutant library to investigate the functional outputs of c-di-GMP metabolism in Pseudomonas aeruginosa PA14.
Appl Environ Microbiol 2014 Mar 21;
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; 306(7):L698-707
PMID: 24487390

Bahl CD, Hvorecny KL, Bridges AA, Ballok AE, Bomberger JM, Cady KC, O'Toole GA, Madden DR
Signature motifs identify an acinetobacter cif virulence factor with epoxide hydrolase activity.
J Biol Chem 2014 Mar 14; 289(11):7460-9
PMID: 24474692

El-Kirat-Chatel S, Boyd CD, O'Toole GA, Dufrene YF
Single-molecule analysis of Pseudomonas fluorescens footprints.
ACS Nano 2014 Feb 25; 8(2):1690-8
PMID: 24456070

Price KE, Hampton TH, Gifford AH, Dolben EL, Hogan DA, Morrison HG, Sogin ML, O'Toole GA
Unique microbial communities persist in individual cystic fibrosis patients throughout a clinical exacerbation.
Microbiome 2013 Nov 1; 1(1):27
PMID: 24451123

Musafer HK, Kuchma SL, Naimie AA, Schwartzman JD, Al-Mathkhury HJ, O'Toole GA
Investigating the Link Between Imipenem Resistance and Biofilm Formation by Pseudomonas aeruginosa.
Microb Ecol 2014 Jan 17;
PMID: 24435545

Dane EL, Ballok AE, O'Toole GA, Grinstaff MW
Synthesis of Bioinspired Carbohydrate Amphiphiles that Promote and Inhibit Biofilms.
Chem Sci 2014 Feb 1; 5(2)
PMID: 24376911

Gifford AH, Alexandru DM, Li Z, Dorman DB, Moulton LA, Price KE, Hampton TH, Sogin ML, Zuckerman JB, Parker HW, Stanton BA, O'Toole GA
Iron supplementation does not worsen respiratory health or alter the sputum microbiome in cystic fibrosis.
J Cyst Fibros 2014 May; 13(3):311-8
PMID: 24332997

Ballok AE, O'Toole GA
Pouring salt on a wound: Pseudomonas aeruginosa virulence factors alter Na+ and Cl- flux in the lung.
J Bacteriol 2013 Sep; 195(18):4013-9
PMID: 23836869