title: Phosphoenolpyruvate Phosphotransferase System Components Modulate Gene Transcription and Virulence of Borrelia burgdorferi.
abstract: The phosphoenolpyruvate phosphotransferase system (PEP-PTS) and adenylate cyclase (AC) IV (encoded by BB0723 [cyaB]) are well conserved in different species of Borrelia. However, the functional roles of PEP-PTS and AC in the infectious cycle of Borrelia have not been characterized previously. We examined 12 PEP-PTS transporter component mutants by needle inoculation of mice to assess their ability to cause mouse infection. Transposon mutants with mutations in the EIIBC components (ptsG) (BB0645, thought to be involved in glucose-specific transport) were unable to cause infection in mice, while all other tested PEP-PTS mutants retained infectivity. Infectivity was partially restored in an in trans-complemented strain of the ptsG mutant. While the ptsG mutant survived normally in unfed as well as fed ticks, it was unable to cause infection in mice by tick transmission, suggesting that the function of ptsG is essential to establish infection by either needle inoculation or tick transmission. In Gram-negative organisms, the regulatory effects of the PEP-PTS are mediated by adenylate cyclase and cyclic AMP (cAMP) levels. A recombinant protein encoded by B. burgdorferi BB0723 (a putative cyaB homolog) was shown to have adenylate cyclase activity in vitro; however, mutants with mutations in this gene were fully infectious in the tick-mouse infection cycle, indicating that its function is not required in this process. By transcriptome analysis, we demonstrated that the ptsG gene may directly or indirectly modulate gene expression of Borrelia burgdorferi. Overall, the PEP-PTS glucose transporter PtsG appears to play important roles in the pathogenesis of B. burgdorferi that extend beyond its transport functions.
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA Bijay.K.Khajanchi@uth.tmc.edu.
authors.forename: Bijay K
authors.initials: BK
authors.lastname: Khajanchi
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Odeh
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Lihui
authors.initials: L
authors.lastname: Gao
authors.affiliation: Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Jacobs
authors.affiliation: Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, USA.
authors.forename: Mario T
authors.initials: MT
authors.lastname: Philipp
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA Department of Microbiology and Molecular Genetics, Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Steven J
authors.identifier: http://orcid.org/0000-0002-2501-8034
authors.initials: SJ
authors.lastname: Norris
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C031629:phosphoenolpyruvate-glucose phosphotransferase