Borrelia Projects: This research focuses on the physiology, biochemistry, gene regulation, and pathogenesis of Borrelia burgdorferi, the causative agent of Lyme disease in humans. B. burgdorferi faces several environmental and immunological challenges during its infective cycle and must alter (regulate) gene expression to successfully adapt to these conditions.
Analysis of the B. burgdorferi genome sequence has revealed that there are very few known regulatory proteins in this bacterium. Conspicuously absent are global regulatory proteins such as CRP, LexA, Fnr, IHF, Lrp, and the sigma factors involved in the heat shock response, ┐σ32 and σ24.
This suggests that, compared to other well-characterized pathogenic bacterial systems, the global regulatory systems operating in B. burgdorferi are relatively simple. Clearly, these systems are required for B. burgdorferi to adapt as it encounters very different environments during transfer from an animal reservoir to the tick and then to a human host.
Research efforts in this group have focused on three important regulatory proteins: 1) BosR, a Zn-dependent transcriptional activator that regulates key antioxidant enzymes; 2) σ54, an alternate sigma factor that also regulates certain parts of the oxidative stress response and regulates the osmotic stress response; and 3) vs., which controls the stationary phase of growth and the expression of genes that are critical to the pathogenesis of Lyme disease.
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Dr. Gherardini received his doctorate in 1987 from the University of Illinois, studying enzymes involved in the utilization of galactomannans by Bacteroides ovatus. From 1991 to 2001, he was a tenured professor in the Department of Microbiology at the University of Georgia. In 2001, Dr. Gherardini joined the Rocky Mountain Laboratories, where he is chief of the Gene Regulation Section and a senior investigator in the Laboratory of Zoonotic Pathogens.
Back row left to right: Sebastien Bontemps-Gallo, Sandy Stewart, Kevin Lawrence, Dan Dulebohn. Front row left to right: Katelyn Fischer, Crystal Richards, Frank Gherardini.
Richards CL, Lawrence KA, Su H, Yang Y, Yang XF, Dulebohn DP, Gherardini FC. Acetyl-phosphate is not a global regulatory bridge between virulence and central metabolism in Borrelia burgdorferi. PLoS One. 2015 Dec 17;10(12):e0144472.
Troxell B, Zhang JJ, Bourret TJ, Zeng MY, Blum J, Gherardini F, Hassan HM, Yang XF. Pyruvate protects pathogenic spirochetes from H2O2 killing. PLoS One. 2014 Jan 2;9(1):e84625
Gherardini FC. Borrelia burgdorferi HtrA may promote dissemination and irritation. Mol Microbiol. 2013 Oct;90(2):209-13.
Bourret TJ, Boylan JA, Lawrence KA, Gherardini FC. Nitrosative damage to free and zinc-bound cysteine thiols underlies nitric oxide toxicity in wild-type Borrelia burgdorferi. Mol Microbiol. 2011 Jul;81(1):259-73.
Xu H, Caimano MJ, Lin T, He M, Radolf JD, Norris SJ, Gherardini F, Wolfe AJ, Yang XF. Role of acetyl-phosphate in activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi. PLoS Pathog. 2010 Sep 16;6(9):e1001104.
Jewett MW, Lawrence KA, Bestor A, Byram R, Gherardini F, Rosa PA. GuaA and GuaB are essential for Borrelia burgdorferi survival in the tick-mouse infection cycle. J Bacteriol. 2009 Oct;191(20):6231-41.
Lawrence KA, Jewett MW, Rosa PA, Gherardini FC. Borrelia burgdorferi bb0426 encodes a 2'-deoxyribosyltransferase that plays a central role in purine salvage. Mol Microbiol. 2009 Jun;72(6):1517-29.
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Last Updated February 23, 2016