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Spirochaete flagella hook proteins self-catalyse a lysinoalanine covalent crosslink for motility.

Miller MR; Miller KA; Bian J; James ME; Zhang S; Lynch MJ; Callery PS; Hettick JM; Cockburn A; Liu J; Li C; Crane BR; Charon NW

Nat Microbiol 2016 Oct; 1(10):16134

https://doi.org/10.1038/nmicrobiol.2016.134

20048556

Spirochaetes are bacteria responsible for several serious diseases, including Lyme disease (Borrelia burgdorferi), syphilis (Treponema pallidum) and leptospirosis (Leptospira interrogans), and contribute to periodontal diseases (Treponema denticola) 1. These spirochaetes employ an unusual form of flagella-based motility necessary for pathogenicity; indeed, spirochaete flagella (periplasmic flagella) reside and rotate within the periplasmic space 2-11. The universal joint or hook that links the rotary motor to the filament is composed of approximately 120-130 FlgE proteins, which in spirochaetes form an unusually stable, high-molecular-weight complex 9,12-17. In other bacteria, the hook can be readily dissociated by treatments such as heat 18. In contrast, spirochaete hooks are resistant to these treatments, and several lines of evidence indicate that the high-molecular-weight complex is the consequence of covalent crosslinking 12,13,17. Here, we show that T. denticola FlgE self-catalyses an interpeptide crosslinking reaction between conserved lysine and cysteine, resulting in the formation of an unusual lysinoalanine adduct that polymerizes the hook subunits. Lysinoalanine crosslinks are not needed for flagellar assembly, but they are required for cell motility and hence infection. The self-catalytic nature of FlgE crosslinking has important implications for protein engineering, and its sensitivity to chemical inhibitors provides a new avenue for the development of antimicrobials targeting spirochaetes.

Bacteria; Diseases; Lyme disease; Borrelia burgdorferi infection; Periodontal disorders; Pathogenicity; Proteins; Cell function; Cellular function; Antimicrobials; Chemical properties

Nyles W.Charon, Department of Microbiology, Immunology and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia 26506

20161001

Other

ncharon@hsc.wvu.edu

2017

10

2058-5276

HELD

Manufacturing

Nature Microbiology

WV