title: The Borrelia burgdorferi CheY3 response regulator is essential for chemotaxis and completion of its natural infection cycle.
abstract: Borrelia burgdorferi possesses a sophisticated and complex chemotaxis system, but how the organism utilizes this system in its natural enzootic life cycle is poorly understood. Of the three CheY chemotaxis response regulators in B. burgdorferi, we found that only deletion of cheY3 resulted in an altered motility and significantly reduced chemotaxis phenotype. Although ΔcheY3 maintained normal densities in unfed ticks, their numbers were significantly reduced in fed ticks compared with the parental or cheY3-complemented spirochetes. Importantly, mice fed upon by the ΔcheY3-infected ticks did not develop a persistent infection. Intravital confocal microscopy analyses discovered that the ΔcheY3 spirochetes were motile within skin, but appeared unable to reverse direction and perform the characteristic backward-forward motility displayed by the parental strain. Subsequently, the ΔcheY3 became 'trapped' in the skin matrix within days of inoculation, were cleared from the skin needle-inoculation site within 96 h post-injection and did not disseminate to distant tissues. Interestingly, although ΔcheY3 cells were cleared within 96 h post-injection, this attenuated infection elicited significant levels of B. burgdorferi-specific IgM and IgG. Taken together, these data demonstrate that cheY3-mediated chemotaxis is crucial for motility, dissemination and viability of the spirochete both within and between mice and ticks.
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Novak
authors.affiliation: Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH, USA.
authors.forename: Padmapriya
authors.initials: P
authors.lastname: Sekar
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Ki Hwan
authors.initials: KH
authors.lastname: Moon
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Akarsh
authors.initials: A
authors.lastname: Manne
authors.affiliation: Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH, USA.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wooten
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Md A
authors.initials: MA
authors.lastname: Motaleb
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001096:Arachnid Vectors / Q000382:microbiology*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D002633:Chemotaxis; D017353:Gene Deletion; D015870:Gene Expression; D005816:Genetic Complementation Test; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D018884:Ixodes / Q000382:microbiology*; D008193:Lyme Disease / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000635:transmission; D000072236:Methyl-Accepting Chemotaxis Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012867:Skin / Q000382:microbiology / Q000473:pathology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000072236:Methyl-Accepting Chemotaxis Proteins