Characterization of the Inner Membrane Protein BB0173 from Borrelia Burgdorferi

Overview

Journal BMC Microbiol

Publisher Biomed Central

Specialty Microbiology

Date 2017 Nov 24

PMID 29166863

Citations 1

Authors

Christina M Brock

Manuel Bano-Polo

Maria J Garcia-Murria

Ismael Mingarro

Maria Esteve-Gasent

Affiliations

Soon will be listed here.

Abstract

Background: The bacterial spirochete Borrelia burgdorferi is the causative agent of the most commonly reported arthropod-borne illness in the United States, Lyme disease. A family of proteins containing von Willebrand Factor A (VWFA) domains adjacent to a MoxR AAA+ ATPase have been found to be highly conserved in the genus Borrelia. Previously, a VWFA domain containing protein of B. burgdorferi, BB0172, was determined to be an outer membrane protein capable of binding integrin α3β1. In this study, the characterization of a new VWFA domain containing membrane protein, BB0173, is evaluated in order to define the location and topology of this multi-spanning membrane protein. In addition, functional predictions are made.

Results: Our results show that BB0173, in contrast to BB0172, is an inner membrane protein, in which the VWFA domain is exposed to the periplasmic space. Further, BB0173 was predicted to have an aerotolerance regulator domain, and expression of BB0173 and the surrounding genes was evaluated under aerobic and microaerophilic conditions, revealing that these genes are downregulated under aerobic conditions. Since the VWFA domain containing proteins of B. burgdorferi are highly conserved, they are likely required for survival of the pathogen through sensing diverse environmental oxygen conditions.

Conclusions: Presently, the complex mechanisms that B. burgdorferi uses to detect and respond to environmental changes are not completely understood. However, studying the mechanisms that allow B. burgdorferi to survive in the highly disparate environments of the tick vector and mammalian host could allow for the development of novel methods of preventing acquisition, survival, or transmission of the spirochete. In this regard, a putative membrane protein, BB0173, was characterized. BB0173 was found to be highly conserved across pathogenic Borrelia, and additionally contains several truly transmembrane domains, and a Bacteroides aerotolerance-like domain. The presence of these functional domains and the highly conserved nature of this protein, strongly suggests a required function of BB0173 in the survival of B. burgdorferi.

Citing Articles

Leptospira interrogans Bat proteins impair host hemostasis by fibrinogen cleavage and platelet aggregation inhibition.

Passalia F, Heinemann M, de Andrade S, Nascimento A, Vieira M Med Microbiol Immunol. 2020; 209(2):201-213.

PMID: 32078713 DOI: 10.1007/s00430-020-00664-4.

References

Neudorf K, Vanderlinde E, Tambalo D, Yost C . A previously uncharacterized tetratricopeptide-repeat-containing protein is involved in cell envelope function in Rhizobium leguminosarum. Microbiology (Reading). 2014; 161(Pt 1):148-157. DOI: 10.1099/mic.0.082420-0. View

Behera A, Durand E, Cugini C, Antonara S, Bourassa L, Hildebrand E . Borrelia burgdorferi BBB07 interaction with integrin alpha3beta1 stimulates production of pro-inflammatory mediators in primary human chondrocytes. Cell Microbiol. 2007; 10(2):320-31. PMC: 2586958. DOI: 10.1111/j.1462-5822.2007.01043.x. View

Ojaimi C, Brooks C, Casjens S, Rosa P, Elias A, Barbour A . Profiling of temperature-induced changes in Borrelia burgdorferi gene expression by using whole genome arrays. Infect Immun. 2003; 71(4):1689-705. PMC: 152086. DOI: 10.1128/IAI.71.4.1689-1705.2003. View

Parveen N, Caimano M, Radolf J, Leong J . Adaptation of the Lyme disease spirochaete to the mammalian host environment results in enhanced glycosaminoglycan and host cell binding. Mol Microbiol. 2003; 47(5):1433-44. DOI: 10.1046/j.1365-2958.2003.03388.x. View

Radolf J, Caimano M, Stevenson B, Hu L . Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nat Rev Microbiol. 2012; 10(2):87-99. PMC: 3313462. DOI: 10.1038/nrmicro2714. View

Esteve-Gassent M, Smith 2nd T, Small C, Thomas D, Seshu J . Absence of sodA Increases the Levels of Oxidation of Key Metabolic Determinants of Borrelia burgdorferi. PLoS One. 2015; 10(8):e0136707. PMC: 4556403. DOI: 10.1371/journal.pone.0136707. View

Arnold K, Bordoli L, Kopp J, Schwede T . The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics. 2005; 22(2):195-201. DOI: 10.1093/bioinformatics/bti770. View

Steere A, Malawista S, Bartenhagen N, Spieler P, Newman J, Rahn D . The clinical spectrum and treatment of Lyme disease. Yale J Biol Med. 1984; 57(4):453-61. PMC: 2590003. View

Yang X, Coleman A, Anguita J, Pal U . A chromosomally encoded virulence factor protects the Lyme disease pathogen against host-adaptive immunity. PLoS Pathog. 2009; 5(3):e1000326. PMC: 2644780. DOI: 10.1371/journal.ppat.1000326. View

10.

Rahn D . Lyme disease: clinical manifestations, diagnosis, and treatment. Semin Arthritis Rheum. 1991; 20(4):201-18. DOI: 10.1016/0049-0172(91)90017-t. View

11.

Esteve-Gassent M, Elliott N, Seshu J . sodA is essential for virulence of Borrelia burgdorferi in the murine model of Lyme disease. Mol Microbiol. 2008; 71(3):594-612. DOI: 10.1111/j.1365-2958.2008.06549.x. View

12.

Stanek G, Wormser G, Gray J, Strle F . Lyme borreliosis. Lancet. 2011; 379(9814):461-73. DOI: 10.1016/S0140-6736(11)60103-7. View

13.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

14.

Tokarz R, Anderton J, Katona L, Benach J . Combined effects of blood and temperature shift on Borrelia burgdorferi gene expression as determined by whole genome DNA array. Infect Immun. 2004; 72(9):5419-32. PMC: 517457. DOI: 10.1128/IAI.72.9.5419-5432.2004. View

15.

Coburn J, Chege W, Magoun L, Bodary S, Leong J . Characterization of a candidate Borrelia burgdorferi beta3-chain integrin ligand identified using a phage display library. Mol Microbiol. 1999; 34(5):926-40. DOI: 10.1046/j.1365-2958.1999.01654.x. View

16.

Martinez-Gil L, Perez-Gil J, Mingarro I . The surfactant peptide KL4 sequence is inserted with a transmembrane orientation into the endoplasmic reticulum membrane. Biophys J. 2008; 95(6):L36-8. PMC: 2527282. DOI: 10.1529/biophysj.108.138602. View

17.

Wood E, Tamborero S, Mingarro I, Esteve-Gassent M . BB0172, a Borrelia burgdorferi outer membrane protein that binds integrin α3β1. J Bacteriol. 2013; 195(15):3320-30. PMC: 3719542. DOI: 10.1128/JB.00187-13. View

18.

Schmittgen T, Livak K . Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3(6):1101-8. DOI: 10.1038/nprot.2008.73. View

19.

Parveen N, Leong J . Identification of a candidate glycosaminoglycan-binding adhesin of the Lyme disease spirochete Borrelia burgdorferi. Mol Microbiol. 2000; 35(5):1220-34. DOI: 10.1046/j.1365-2958.2000.01792.x. View

20.

Antonara S, Chafel R, LaFrance M, Coburn J . Borrelia burgdorferi adhesins identified using in vivo phage display. Mol Microbiol. 2007; 66(1):262-76. PMC: 2651023. DOI: 10.1111/j.1365-2958.2007.05924.x. View