Borrelia burgdorferi is a highly motile and invasive spirochete pathogen causing Lyme disease, the most common vector-borne infection in the United States. Periplasmic flagella, the main organelles for motility, are essential for the distint morphology, motility and infectious life cycle of B. burgdorferi. The periplasmic flagella are distinct from the external flagella in the model systems Escherichia coli and Salmonella enterica, as they are enclosed within the outer membrane and their flagellar motors are considerably larger and more complex. Importantly, owing to its small cell diameter and highly ordered flagellar motors at the cell tip, B. burgdorferi is emerging as a unique paradigm for in situ structural analysis of the periplasmic flagella by employing the ground-breaking methodology of cryo-electron tomography (cryo-ET). During the previous funding period, we have generated a large B. burgdorferi library of over 40 different flagellar and chemotaxis mutants in collaboration with Drs. Steven Norris, Md Motaleb, Chunhao Li and Nyles Charon. Significant progress has been made in understanding the unique periplasmic flagella and their dramatic impacts in the unique spirochetal motility and morphology. The objective of this application is to understand three fundamental aspects of the periplasmic flagella: 1) the structural basis of the flagellar rotation; 2) the flagellar switching mechanism; and 3) the structure and mechanism of the flagellar type III secretion apparatus. Together with genetic and biochemical approaches, cryo-ET will be utilized to determine the structure/function relationship of the spirochetal flagellar motor in native cellular environment.

Public Health Relevance

Spirochetes are a distinctive group of bacteria of significant importance in human health. Motility is essential for spirochetes to infect and disseminate in mammalian hosts. The spirochetal motility is unique as the entire bacterium is involved in translocation without the involvement of external appendages. The motility is driven by periplasmic flagella, which are enclosed within the outer membrane and are distinct from the external flagella in the model systems Escherichia coli and Salmonella enterica. Thus, a better understanding of the unique aspects of periplasmic flagella in infectious pathogens could potentially lead to the development of novel drugs that specifically prohibit unique spirochetal motility and prevent major human diseases, such as syphilis, leptospirosis, and Lyme disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Ilias, Maliha R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
Schools of Medicine
New Haven
United States
Zip Code
Chetrit, David; Hu, Bo; Christie, Peter J et al. (2018) A unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channel. Nat Microbiol 3:678-686
Moon, Ki Hwan; Zhao, Xiaowei; Xu, Hui et al. (2018) A tetratricopeptide repeat domain protein has profound effects on assembly of periplasmic flagella, morphology and motility of the lyme disease spirochete Borrelia burgdorferi. Mol Microbiol 110:634-647
Qin, Zhuan; Hu, Bo; Liu, Jun (2018) Visualizing Chemoreceptor Arrays in Bacterial Minicells by Cryo-Electron Tomography and Subtomogram Analysis. Methods Mol Biol 1729:187-199
Zhu, Shiwei; Nishikino, Tatsuro; Hu, Bo et al. (2017) Molecular architecture of the sheathed polar flagellum in Vibrio alginolyticus. Proc Natl Acad Sci U S A 114:10966-10971
Hu, Bo; Lara-Tejero, Maria; Kong, Qingke et al. (2017) In Situ Molecular Architecture of the Salmonella Type III Secretion Machine. Cell 168:1065-1074.e10
Kurniyati, Kurni; Kelly, John F; Vinogradov, Evgeny et al. (2017) A novel glycan modifies the flagellar filament proteins of the oral bacterium Treponema denticola. Mol Microbiol 103:67-85
Miller, Michael R; Miller, Kelly A; Bian, Jiang et al. (2016) Spirochaete flagella hook proteins self-catalyse a lysinoalanine covalent crosslink for motility. Nat Microbiol 1:16134
Moon, Ki Hwan; Zhao, Xiaowei; Manne, Akarsh et al. (2016) Spirochetes flagellar collar protein FlbB has astounding effects in orientation of periplasmic flagella, bacterial shape, motility, and assembly of motors in Borrelia burgdorferi. Mol Microbiol 102:336-348
Wunder Jr, Elsio A; Figueira, Cláudio P; Benaroudj, Nadia et al. (2016) A novel flagellar sheath protein, FcpA, determines filament coiling, translational motility and virulence for the Leptospira spirochete. Mol Microbiol 101:457-70
Zhang, Kai; Liu, Jun; Charon, Nyles W et al. (2016) Hypothetical Protein BB0569 Is Essential for Chemotaxis of the Lyme Disease Spirochete Borrelia burgdorferi. J Bacteriol 198:664-72

Showing the most recent 10 out of 38 publications