Both Decorin-Binding Proteins A and B Are Critical for the Overall Virulence of Borrelia burgdorferi

ABSTRACT Both decorin-binding proteins (DbpA and DbpB) of the Lyme disease spirochete Borrelia burgdorferi bind decorin and glycosaminoglycans, two important building blocks of proteoglycans that are abundantly found in the extracellular matrix (ECM) and connective tissues as well as on cell surfaces of mammals. As an extracellular pathogen, B. burgdorferi resides primarily in the ECM and connective tissues and between host cells during mammalian infection. The interactions of B. burgdorferi with these host ligands mediated by DbpA and DbpB potentially influence various aspects of infection. Here, we show that both DbpA and DbpB are critical for the overall virulence of B. burgdorferi in the murine host. Disruption of the dbpBA locus led to nearly a 104-fold increase in the 50% infectious dose (ID50). Complementation of the mutant with either dbpA or dbpB reduced the ID50 from over 104 to roughly 103 organisms. Deletion of the dbpBA locus affected colonization in all tissues of infected mice. The lack of dbpA alone precluded the pathogen from colonizing the heart tissue, and B. burgdorferi deficient for DbpB was recovered only from 42% of the heart specimens of infected mice. Although B. burgdorferi lacking either dbpA or dbpB was consistently grown from joint specimens of almost all infected mice, it generated bacterial loads significantly lower than the control. The deficiency in either DbpA or DbpB did not reduce the bacterial load in skin, but lack of both significantly did. Taken together, the study results indicate that neither DbpA nor DbpB is essential for mammalian infection but that both are critical for the overall virulence of B. burgdorferi.

[1]  S. Newman,et al.  Hidden in plain sight: Borrelia burgdorferi and the extracellular matrix. , 2007, Trends in microbiology.

[2]  Qilong Xu,et al.  Increasing the Interaction of Borrelia burgdorferi with Decorin Significantly Reduces the 50 Percent Infectious Dose and Severely Impairs Dissemination , 2007, Infection and Immunity.

[3]  P. Shaw,et al.  The critical role of the linear plasmid lp36 in the infectious cycle of Borrelia burgdorferi , 2007, Molecular microbiology.

[4]  Qilong Xu,et al.  Increasing the Recruitment of Neutrophils to the Site of Infection Dramatically Attenuates Borrelia burgdorferi Infectivity1 , 2007, The Journal of Immunology.

[5]  Qilong Xu,et al.  Identification of an ospC operator critical for immune evasion of Borrelia burgdorferi , 2007, Molecular microbiology.

[6]  Qilong Xu,et al.  The dbpBA Locus of Borrelia burgdorferi Is Not Essential for Infection of Mice , 2006, Infection and Immunity.

[7]  G. Wormser,et al.  Comparative Genome Hybridization Reveals Substantial Variation among Clinical Isolates of Borrelia burgdorferi Sensu Stricto with Different Pathogenic Properties , 2006, Journal of bacteriology.

[8]  S. Akira,et al.  Identification of a TLR-Independent Pathway for Borrelia burgdorferi-Induced Expression of Matrix Metalloproteinases and Inflammatory Mediators through Binding to Integrin α3β11 , 2006, The Journal of Immunology.

[9]  E. Fikrig,et al.  Borrelia burgdorferi Lacking BBK32, a Fibronectin-Binding Protein, Retains Full Pathogenicity , 2006, Infection and Immunity.

[10]  J. Bono,et al.  Bgp, a Secreted Glycosaminoglycan-Binding Protein of Borrelia burgdorferi Strain N40, Displays Nucleosidase Activity and Is Not Essential for Infection of Immunodeficient Mice , 2006, Infection and Immunity.

[11]  Maria Labandeira-Rey,et al.  Inactivation of the fibronectin‐binding adhesin gene bbk32 significantly attenuates the infectivity potential of Borrelia burgdorferi , 2006, Molecular microbiology.

[12]  J. Leong,et al.  Fibronectin Binding Protein BBK32 of the Lyme Disease Spirochete Promotes Bacterial Attachment to Glycosaminoglycans , 2006, Infection and Immunity.

[13]  E. Fikrig,et al.  Association of Linear Plasmid 28-1 with an Arthritic Phenotype of Borrelia burgdorferi , 2005, Infection and Immunity.

[14]  J. Coburn,et al.  Solving a sticky problem: new genetic approaches to host cell adhesion by the Lyme disease spirochete , 2005, Molecular microbiology.

[15]  Haruo Watanabe,et al.  BBE02 Disruption Mutants of Borrelia burgdorferi B31 Have a Highly Transformable, Infectious Phenotype , 2004, Infection and Immunity.

[16]  E. Fikrig,et al.  Protective niche for Borrelia burgdorferi to evade humoral immunity. , 2004, The American journal of pathology.

[17]  J. Bono,et al.  New Antibiotic Resistance Cassettes Suitable for Genetic Studies in Borrelia burgdorferi , 2003, Journal of Molecular Microbiology and Biotechnology.

[18]  Maria Labandeira-Rey,et al.  The Absence of Linear Plasmid 25 or 28-1 of Borrelia burgdorferi Dramatically Alters the Kinetics of Experimental Infection via Distinct Mechanisms , 2003, Infection and Immunity.

[19]  J. Leong,et al.  Decorin-binding proteins A and B confer distinct mammalian cell type-specific attachment by Borrelia burgdorferi, the Lyme disease spirochete , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  S. Norris,et al.  A plasmid‐encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host , 2003, Molecular microbiology.

[21]  S. Norris,et al.  Decreased Electroporation Efficiency in Borrelia burgdorferi Containing Linear Plasmids lp25 and lp56: Impact on Transformation of Infectious B. burgdorferi , 2002, Infection and Immunity.

[22]  Barbara J. B. Johnson,et al.  Mapping the Ligand-Binding Region of Borrelia burgdorferi Fibronectin-Binding Protein BBK32 , 2001, Infection and Immunity.

[23]  J. Coburn,et al.  Delineation of Borrelia burgdorferi p66 Sequences Required for Integrin αIIbβ3 Recognition , 2001, Infection and Immunity.

[24]  B. P. Guo,et al.  Resistance to Lyme disease in decorin-deficient mice. , 2001, The Journal of clinical investigation.

[25]  Maria Labandeira-Rey,et al.  Decreased Infectivity in Borrelia burgdorferi Strain B31 Is Associated with Loss of Linear Plasmid 25 or 28-1 , 2001, Infection and Immunity.

[26]  S. Norris,et al.  Correlation between plasmid content and infectivity in Borrelia burgdorferi. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[27]  J. Radolf,et al.  Decorin-Binding Protein A (DbpA) of Borrelia burgdorferi Is Not Protective When Immunized Mice Are Challenged via Tick Infestation and Correlates with the Lack of DbpA Expression by B. burgdorferi in Ticks , 2000, Infection and Immunity.

[28]  J. Leong,et al.  Identification of a candidate glycosaminoglycan‐binding adhesin of the Lyme disease spirochete Borrelia burgdorferi , 2000, Molecular microbiology.

[29]  S. Bodary,et al.  Characterization of a candidate Borrelia burgdorferiβ3‐chain integrin ligand identified using a phage display library , 1999, Molecular microbiology.

[30]  J. Leong,et al.  Strain Variation in Glycosaminoglycan Recognition Influences Cell-Type-Specific Binding by Lyme Disease Spirochetes , 1999, Infection and Immunity.

[31]  Barbara J. B. Johnson,et al.  Identification of a 47 kDa fibronectin‐binding protein expressed by Borrelia burgdorferi isolate B31 , 1998, Molecular microbiology.

[32]  B. P. Guo,et al.  Decorin‐binding adhesins from Borrelia burgdorferi , 1998, Molecular microbiology.

[33]  J. Radolf,et al.  Decorin-Binding Protein of Borrelia burgdorferi Is Encoded within a Two-Gene Operon and Is Protective in the Murine Model of Lyme Borreliosis , 1998, Infection and Immunity.

[34]  J. Weis,et al.  Immunity to Lyme disease: protection, pathology and persistence. , 1996, Current opinion in immunology.

[35]  Jean Côté,et al.  Lyme Disease , 1991, International journal of dermatology.

[36]  S. Barthold Infectivity of Borrelia burgdorferi relative to route of inoculation and genotype in laboratory mice. , 1991, The Journal of infectious diseases.

[37]  W. Burgdorfer,et al.  Development of Borrelia burgdorferi in Ixodid Tick Vectors , 1988, Annals of the New York Academy of Sciences.

[38]  L. Reed,et al.  A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS , 1938 .