Frank Gherardini, Ph.D.

Chief, Gene Regulation Section

Major Areas of Research

  • Physiology, biochemistry, gene regulation, and pathogenesis of Borrelia burgdorferi and Borrelia hermsii

Program Description

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.

Biography

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 Bacteriology.

Research Group

Members of the Gene Regulation Section
Credit: NIAID

Members of the Gene Regulation Section

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.

Selected Publications

Bontemps-Gallo S, Lawrence KA, Richards CL, Gherardini FC. Borrelia burgdorferi genes, bb0639-0642, encode a putative putrescine/spermidine transport system PotABCD that is spermidine specific and essential for cell survival. Mol Microbiol 2018 Feb.

https://www.ncbi.nlm.nih.gov/pubmed/29476656

Dulebohn DP, Richards CL, Su H, Lawrence KA, Gherardini FC. Weak organic acids decrease borrelia burgdorferi cytoplasmic pH, eliciting an acid stress response and impacting RpoN- and RpoS-dependent gene expression. Front Microbiol. 2017 Sep 29;8:1734.

Bourret TJ, Lawrence KA, Shaw JA, Lin T, Norris SJ, Gherardini FC. The nucleotide excision repair pathway protects Borrelia burgdorferi from nitrosative stress in Ixodes scapularis ticks. Front Microbiol. 2016 Sep 7;7:1397.

Bontemps-Gallo S, Lawrence K, Gherardini FC. Two different virulence-related regulatory pathways in Borrelia burgdorferi are directly affected by osmotic fluxes in the blood meal of feeding Ixodes ticks. PLoS Pathog. 2016 Aug 15;12(8):e1005791.  

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 burgdorferiPLoS One. 2015 Dec 17;10(12):e0144472.

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 burgdorferiMol Microbiol. 2011 Jul;81(1):259-73.

Raffel SJ, Williamson BN, Schwan TG, Gherardini FC. Colony formation in solid medium by the relapsing fever spirochetes Borrelia hermsii and Borrelia turicatae. Ticks Tick Borne Dis. 2017 Nov.

Visit PubMed for a complete publications listing.

 

Content last reviewed on February 28, 2018