title: Middle region of the Borrelia burgdorferi surface-located protein 1 (Lmp1) interacts with host chondroitin-6-sulfate and independently facilitates infection.
abstract: Borrelia burgdorferi surface-located membrane protein 1, also known as Lmp1, has been shown to play critical roles in pathogen evasion of host-acquired immune defences, thereby facilitating persistent infection. Lmp1 possesses three regions representing potentially discrete domains: Lmp1N, Lmp1M and Lmp1C. Because of its insignificant homology to known proteins, how Lmp1 or its specific regions contribute to microbial biology and infection remains enigmatic. Here, we show that distinct from Lmp1N and Lmp1C, Lmp1M is composed of at least 70% alpha helices and completely lacks recognizable beta sheets. The region binds to host glycosaminoglycan chondroitin-6-sulfate molecules and facilitates mammalian cell attachment, suggesting an adhesin function of Lmp1M. Phenotypic analysis of the Lmp1-deficient mutant engineered to produce Lmp1M on the microbial surface suggests that Lmp1M can independently support B. burgdorferi infectivity in murine hosts. Further exploration of functions of Lmp1 distinct regions will shed new light on the intriguing biology and infectivity of spirochetes and help develop novel interventions to combat Lyme disease.
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, 20742, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA.
authors.forename: Yi-Pin
authors.initials: YP
authors.lastname: Lin
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, 9600 Gudelsky Drive, Rockville, MD, 20850, USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Heselpoth
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, 20742, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Buyuktanir
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, 20742, USA.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, 20742, USA.
authors.forename: Faith
authors.initials: F
authors.lastname: Kung
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, 20742, USA.|Institute for Bioscience and Biotechnology Research, University of Maryland, 9600 Gudelsky Drive, Rockville, MD, 20850, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Nelson
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Leong
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, 20742, USA.
authors.forename: Utpal
authors.initials: U
authors.lastname: Pal
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000502:physiology*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D002809:Chondroitin Sulfates