Gene Regulation Section
Frank Gherardini, Ph.D.
Chief, Gene Regulation Section
Contact: For contact information, search the NIH Enterprise Directory.
Specialty(s): Infectious Disease
Major Areas of Research
- Physiology, biochemistry, gene regulation, and pathogenesis of Borrelia burgdorferi and Borrelia hermsii
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.
Ph.D., 1987, University of Illinois
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.
Richards CL, Raffel SJ, Bontemps-Gallo S, Dulebohn DP, Herbert TC, Gherardini FC. The arginine deaminase system plays distinct roles in Borrelia burgdorferi and Borrelia hermsii. PLoS Pathog. 2022 Mar 14;18(3):e1010370.
Drecktrah D, Hall LS, Crouse B, Schwarz B, Richards C, Bohrnsen E, Wulf M, Long B, Bailey J, Gherardini F, Bosio CM, Lybecker MC, Samuels DS. The glycerol-3-phosphate dehydrogenases GpsA and GlpD constitute the oxidoreductive metabolic linchpin for Lyme disease spirochete host infectivity and persistence in the tick. PLoS Pathog. 2022 Mar 7;18(3):e1010385.
Boyle WK, Richards CL, Dulebohn DP, Zalud AK, Shaw JA, Lovas S, Gherardini FC, Bourret TJ. DksA-dependent regulation of RpoS contributes to Borrelia burgdorferi tick-borne transmission and mammalian infectivity. PLoS Pathog. 2021 Feb 18;17(2):e1009072.
Gherardini FC, Dulebohn DP, Bourret TJ, Richards CL: Metabolism and Physiology of Borrelia. In: L Relapsing Fever Spirochetes: Genomics, Molecular Biology, Host Interactions and Disease Pathogenesis. Edited by Radolf JD, Samuels DS. Poole, UK: Caister Academic Press; 2021: 131-180.
Boyle WK, Hall LS, Armstrong AA, Dulebohn DP, Samuels DS, Gherardini FC, Bourret TJ. Establishment of an in vitro RNA polymerase transcription system: a new tool to study transcriptional activation in Borrelia burgdorferi. Sci Rep. 2020 May 19;10(1):8246.
Saraithong P, Goetting-Minesky MP, Durbin PM, Olson SW, Gherardini FC, Fenno JC. Roles of TroA and TroR in Metalloregulated Growth and Gene Expression in Treponema denticola. J Bacteriol. 2020 Mar 11;202(7):e00770-19.