title: Lyme disease and relapsing fever Borrelia elongate through zones of peptidoglycan synthesis that mark division sites of daughter cells.
abstract: Agents that cause Lyme disease, relapsing fever, leptospirosis, and syphilis belong to the phylum Spirochaetae-a unique lineage of bacteria most known for their long, spiral morphology. Despite the relevance to human health, little is known about the most fundamental aspects of spirochete growth. Here, using quantitative microscopy to track peptidoglycan cell-wall synthesis, we found that the Lyme disease spirochete Borrelia burgdorferi displays a complex pattern of growth. B. burgdorferi elongates from discrete zones that are both spatially and temporally regulated. In addition, some peptidoglycan incorporation occurs along the cell body, with the notable exception of a large region at the poles. Newborn cells inherit a highly active zone of peptidoglycan synthesis at midcell that contributes to elongation for most of the cell cycle. Concomitant with the initiation of nucleoid separation and cell constriction, second and third zones of elongation are established at the 1/4 and 3/4 cellular positions, marking future sites of division for the subsequent generation. Positioning of elongation zones along the cell is robust to cell length variations and is relatively precise over long distances (>30 µm), suggesting that cells ‟sense" relative, as opposed to absolute, cell length to establish zones of peptidoglycan synthesis. The transition from one to three zones of peptidoglycan growth during the cell cycle is also observed in relapsing fever Borrelia. However, this mode of growth does not extend to representative species from other spirochetal genera, suggesting that this distinctive growth mode represents an evolutionary divide in the spirochete phylum.
authors: Microbial Sciences Institute, Yale University, West Haven, CT 06517; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06516; Howard Hughes Medical Institute, Yale University, New Haven, CT 06516;
authors: Brandon Lyon
authors: BL
authors: Jutras
authors: Microbial Sciences Institute, Yale University, West Haven, CT 06517; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06516;
authors: Molly
authors: M
authors: Scott
authors: Microbial Sciences Institute, Yale University, West Haven, CT 06517; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06516;
authors: Bradley
authors: B
authors: Parry
authors: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, United Kingdom;
authors: Jacob
authors: J
authors: Biboy
authors: Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, United Kingdom;
authors: Joe
authors: J
authors: Gray
authors: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, United Kingdom;
authors: Waldemar
authors: W
authors: Vollmer
authors: Microbial Sciences Institute, Yale University, West Haven, CT 06517; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06516; Howard Hughes Medical Institute, Yale University, New Haven, CT 06516; Department of Microbial Pathogenesis, Yale Medical School, New Haven, CT 06516 christine.jacobs-wagner@yale.edu.
authors: Christine
authors: C
authors: Jacobs-Wagner
mesh_terms: D001898:Borrelia / Q000254:growth & development*; D025065:Borrelia burgdorferi / Q000254:growth & development; D002453:Cell Cycle; D006801:Humans; D008193:Lyme Disease / Q000382:microbiology*; D010457:Peptidoglycan / Q000096:biosynthesis*; D012061:Relapsing Fever / Q000382:microbiology*
chemical_list: D010457:Peptidoglycan
keywords: Borrelia burgdorferi; Lyme disease; peptidoglycan; relapsing fever; spirochetes