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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:

 

Classic Spotlight: Quorum Sensing and the Multicellular Life of Unicellular Organisms.
O'Toole GA
J Bacteriol. 2016 Feb 15;198(4):601. doi: 10.1128/JB.00956-15. Epub 2016 Jan 29.
PMID: 26825965

Cystic Fibrosis Lung Infections: Polymicrobial, Complex, and Hard to Treat.
Filkins LM, O'Toole GA
PLoS Pathog. 2015 Dec;11(12):e1005258. doi: 10.1371/journal.ppat.1005258. Epub 2015 Dec 31.
PMID: 26719892

Iron-dependent gene expression in Actinomyces oris.
Mule MP, Giacalone D, Lawlor K, Golden A, Cook C, Lott T, Aksten E, O'Toole GA, Bergeron LJ
J Oral Microbiol. 2015;7:29800. doi: 10.3402/jom.v7.29800. Epub 2015 Dec 16.
PMID: 26685151

Contribution of Physical Interactions to Signaling Specificity between a Diguanylate Cyclase and Its Effector.
Dahlstrom KM, Giglio KM, Collins AJ, Sondermann H, O'Toole GA
MBio. 2015 Dec 15;6(6):e01978-15. doi: 10.1128/mBio.01978-15. Epub 2015 Dec 15.
PMID: 26670387

Classic Spotlight: Before They Were Biofilms.
O'Toole GA
J Bacteriol. 2016 Jan 1;198(1):5. doi: 10.1128/JB.00593-15. Epub 2015 Dec 14.
PMID: 26668270

Mannitol Does Not Enhance Tobramycin Killing of Pseudomonas aeruginosa in a Cystic Fibrosis Model System of Biofilm Formation.
Price KE, Orazi G, Ruoff KL, Hebert WP, O'Toole GA, Mastoridis P
PLoS One. 2015;10(10):e0141192. doi: 10.1371/journal.pone.0141192. Epub 2015 Oct 27.
PMID: 26506004

Tobramycin-Treated Pseudomonas aeruginosa PA14 Enhances Streptococcus constellatus 7155 Biofilm Formation in a Cystic Fibrosis Model System.
Price KE, Naimie AA, Griffin EF, Bay C, O'Toole GA
J Bacteriol. 2015 Oct 19;198(2):237-47. doi: 10.1128/JB.00705-15. Epub 2015 Oct 19.
PMID: 26483523

c-di-GMP and its Effects on Biofilm Formation and Dispersion: a Pseudomonas Aeruginosa Review.
Ha DG, O'Toole GA
Microbiol Spectr. 2015 Apr;3(2):MB-0003-2014. doi: 10.1128/microbiolspec.MB-0003-2014.
PMID: 26104694

Cyclic Di-GMP-Regulated Periplasmic Proteolysis of a Pseudomonas aeruginosa Type Vb Secretion System Substrate.
Cooley RB, Smith TJ, Leung W, Tierney V, Borlee BR, O'Toole GA, Sondermann H
J Bacteriol. 2015 Jun 22;198(1):66-76. doi: 10.1128/JB.00369-15. Epub 2015 Jun 22.
PMID: 26100041

Haemophilus influenzae responds to glucocorticoids used in asthma therapy by modulation of biofilm formation and antibiotic resistance.
Earl CS, Keong TW, An SQ, Murdoch S, McCarthy Y, Garmendia J, Ward J, Dow JM, Yang L, O'Toole GA, Ryan RP
EMBO Mol Med. 2015 May 20;7(8):1018-33. doi: 10.15252/emmm.201505088. Epub 2015 May 20.
PMID: 25995336