The long-term goal of the Nau laboratory is to exploit fundamental knowledge of bacterial pathogenesis and innate immunity to develop innovative therapies against infectious diseases. The host-pathogen interaction is central to our studies, with experiments devoted to both sides of that interaction. Our experimental approaches include genetics, biochemistry, RNA analysis, and various infection models.
One focus of the laboratory is to understand what makes Francisella tularensis, the causative agent of tularemia, pathogenic. A wide range of molecular tools are used to alter gene content and protein expression in a variety of Francisella strains. These experiments characterize virulence factors as well as proteins involved in normal bacterial processes that are central to the microorganism. Virulence factors that investigate include a Francisella protein that inhibits NFκB signaling and the bacterium’s secretion systems. We are also studying a family of proteins that share a common domain and that regulate the outer bacterial envelope. Potential drug targets identified in Francisella strains are also studied in other Gram-negative and Gram-positive bacteria to generalize our findings.
Another focus is to study the host’s response to infection. F. tularensis suppresses innate immune activation through a variety of mechanisms. The Nau lab has focused on inflammation, Toll-like receptor activation, cytokine responses, inhibition of NFκB, intracellular growth in immune and non-immune cells in vitro, and the virulence of bacterial strains in invertebrate and mammalian hosts. The lab also investigates host defenses and inflammation in other conditions, such as aging. Ultimately, we seek to modulate host defenses as a means to augment anti-infective therapies. The laboratory also supports the COBRE Center for Antimicrobial Resistance and Therapeutic Discovery with the Animal Models Core.
Keywords: Francisella tularensis, tularemia, innate immunity, inflammation, Toll-like receptor, NFκB, virulence, pathogenesis, aging, antibiotic resistance
Key Publications:
Talbot GH, Jezek A, Murray BE, Jones RN, Ebright RH, Nau GJ, Rodvold KA, Newland JG, Boucher HW; Infectious Diseases Society of America. Clin Infect Dis. 2019 Feb 1. [Epub ahead of print] PMID: 30715222
Jayamani E, Tharmalingam N, Rajamuthiah R, Coleman JJ, Kim W, Okoli I, Hernandez AM, Lee K, Nau GJ, Ausubel FM, Mylonakis E. Characterization of a Francisella tularensis-Caenorhabditis elegans Pathosystem for the Evaluation of Therapeutic Compounds. Antimicrob Agents Chemother. 2017 Aug 24;61(9). PMC5571314
Brown MJ, Russo BC, O’Dee DM, Schmitt DM, Nau GJ. The contribution of the glycine cleavage system to the pathogenesis of Francisella tularensis. Microbes Infect. 2014 Apr;16(4):300-9. PMC4089098.
Schmitt DM, O’Dee DM, Cowan BN, Birch JW-M, Massella LK, Nau GJ, Horzempa J. Use of resazurin as a novel antimicrobial agent against Francisella tularensis. Front Cell Infect Microbiol. 2013 Dec 6;3:93. PMC3853850
Russo BC, Brown MJ, Nau GJ. MyD88 dependent signaling prolongs survival and reduces bacterial burden during pulmonary infection with virulent Francisella tularensis. Am J Pathol. 2013 Oct;183(4):1223-32. PMC3791678
Russo BC, Horzempa J, O’Dee DM, Schmitt DM, Brown MJ, Carlson PE Jr, Xavier RJ, Nau GJ. A Francisella tularensis locus required for spermine responsiveness is necessary for virulence. Infect Immun. 2011 Sep;79(9):3665-76. PMC3165480
Horzempa J, O’Dee DM, Beer-Stolz D, Franks JM, Clay D, Nau GJ. Invasion of erythrocytes by Francisella tularensis. J Infect Dis. 2011 Jul;204(1):51-9. PMC3105038.
Carlson PE Jr, Horzempa J, O’Dee DM, Robinson CM, Neophytou P, Labrinidis A, Nau GJ. Global transcriptional response to spermine, a component of the intra-macrophage environment, reveals regulation of Francisella gene expression through insertion sequence elements. J Bacteriol. 2009 Nov;191(22):6855-64. Epub 2009 Sep 11. PMC2772466
Horzempa, J, Carlson PE Jr, O’Dee DM, Shanks RM, Nau GJ. Global transcriptional response to mammalian temperature provides new insight into Francisella tularensis pathogenesis. BMC Microbiol. 2008 Oct 8;8:172 PMC2576331
Carlson PE Jr, Carroll JA, O’Dee D, Nau GJ. Modulation of virulence factors in Francisella tularensis determines human macrophage responses. Microb Pathog. 2007 May-Jun;42(5-6):204-14. PMC2699611
Images:
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Contact Information:
Gerard J. Nau, MD, PhD, FIDSA
Rhode Island Hospital
Aldrich 722
593 Eddy St.
Providence, RI 02903
Tel: 401-444-7432
Email: gerard_nau@brown.edu
Additional links of interest:
Infectious Diseases Society of America
American Society for Microbiology
Tularemia International Society
COBRE Center for Antimicrobial Resistance and Therapeutic Discovery (CARTD)