Targeted mutation of the outer membrane protein P66 disrupts attachment of the Lyme disease agent, Borrelia burgdorferi, to integrin alphavbeta3. Proc Natl Acad Sci U S A 2003 Jun 10;100(12):7301-6
Date
05/16/2003Pubmed ID
12748384Pubmed Central ID
PMC165870DOI
10.1073/pnas.1131117100Scopus ID
2-s2.0-0038809086 (requires institutional sign-in at Scopus site) 99 CitationsAbstract
Borrelia burgdorferi, the agent of Lyme disease, expresses several adhesion molecules that are probably required for initial establishment of infection in mammalian hosts, and for colonization of various tissues within the host. The B. burgdorferi outer membrane protein P66 was previously identified as a ligand for beta3-chain integrins by using a variety of biochemical approaches. Although the earlier data suggested that P66 is an adhesin that mediates B. burgdorferi attachment to beta3-chain integrins, lack of genetic systems in B. burgdorferi precluded definitive demonstration of a role for P66 in beta3 integrin attachment by intact borreliae. Recent advances in the genetic manipulation of B. burgdorferi have now made possible the targeted disruption of the p66 gene. Mutants in p66 show dramatically reduced attachment to integrin alphavbeta3. This is, to our knowledge, the first description of the targeted disruption of a candidate B. burgdorferi virulence factor with a known biochemical function that can be quantified, and demonstrates the importance of B. burgdorferi P66 in the attachment of this pathogenic spirochete to a human cell-surface receptor.
Author List
Coburn J, Cugini CAuthor
Jenifer Coburn PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Bacterial AdhesionBacterial Proteins
Binding Sites
Borrelia burgdorferi
Genes, Bacterial
Humans
In Vitro Techniques
Integrin alphaVbeta3
Lyme Disease
Mutation
Porins
