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George A. O'Toole, PhD

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:

 

Co-opting the Lap System of Pseudomonas fluorescens To Reversibly Customize Bacterial Cell Surfaces.
Smith TJ, Sondermann H, O'Toole GA
ACS Synth Biol. 2018 Nov 16;7(11):2612-2617. doi: 10.1021/acssynbio.8b00278. Epub 2018 Oct 16.
PMID: 30278125

Ligand-Mediated Biofilm Formation via Enhanced Physical Interaction between a Diguanylate Cyclase and Its Receptor.
Giacalone D, Smith TJ, Collins AJ, Sondermann H, Koziol LJ, O'Toole GA
MBio. 2018 Jul 10;9(4) pii: e01254-18. doi: 10.1128/mBio.01254-18. Epub 2018 Jul 10.
PMID: 29991582

Special Sections for the 6th ASM Conference on Cell-Cell Communication in Bacteria.
O'Toole GA
J Bacteriol. 2018 Jul 15;200(14) pii: e00271-18. doi: 10.1128/JB.00271-18. Epub 2018 Jun 25.
PMID: 29941545

Type 1 Does the Two-Step: Type 1 Secretion Substrates with a Functional Periplasmic Intermediate.
Smith TJ, Sondermann H, O'Toole GA
J Bacteriol. 2018 Sep 15;200(18) pii: e00168-18. doi: 10.1128/JB.00168-18. Epub 2018 Aug 24.
PMID: 29866808

Multigenerational memory and adaptive adhesion in early bacterial biofilm communities.
Lee CK, de Anda J, Baker AE, Bennett RR, Luo Y, Lee EY, Keefe JA, Helali JS, Ma J, Zhao K, Golestanian R, O'Toole GA, Wong GCL
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4471-4476. doi: 10.1073/pnas.1720071115. Epub 2018 Mar 20.
PMID: 29559526

An N-terminal Retention Module Anchors the Giant Adhesin LapA of <i>Pseudomonas fluorescens</i> at the Cell Surface: A Novel Sub-family of Type I Secretion Systems.
Smith TJ, Font ME, Kelly CM, Sondermann H, O'Toole GA
J Bacteriol. 2018 Feb 5; pii: JB.00734-17. doi: 10.1128/JB.00734-17. Epub 2018 Feb 5.
PMID: 29437852

A Multimodal Strategy Used by a Large c-di-GMP Network.
Dahlstrom KM, Collins AJ, Doing G, Taroni JN, Gauvin TJ, Greene CS, Hogan DA, O'Toole GA
J Bacteriol. 2018 Apr 15;200(8) pii: e00703-17. doi: 10.1128/JB.00703-17. Epub 2018 Mar 26.
PMID: 29311282

Cystic Fibrosis Airway Microbiome: Overturning the Old, Opening the Way for the New.
O'Toole GA
J Bacteriol. 2018 Feb 15;200(4) pii: e00561-17. doi: 10.1128/JB.00561-17. Epub 2018 Jan 24.
PMID: 29084859

Special Meeting Sections for the ASM Conference on Mechanisms of Interbacterial Cooperation and Competition.
O'Toole GA
J Bacteriol. 2017 Nov 15;199(22) pii: e00522-17. doi: 10.1128/JB.00522-17. Epub 2017 Oct 17.
PMID: 29042432

An Antipersister Strategy for Treatment of Chronic Pseudomonas aeruginosa Infections.
Koeva M, Gutu AD, Hebert W, Wager JD, Yonker LM, O'Toole GA, Ausubel FM, Moskowitz SM, Joseph-McCarthy D
Antimicrob Agents Chemother. 2017 Dec;61(12) pii: e00987-17. doi: 10.1128/AAC.00987-17. Epub 2017 Nov 22.
PMID: 28923873