Previous Article | Next Article ![]()
Journal of Bacteriology, October 2001, p. 5855-5861, Vol. 183, No. 20
Department of Microbiology and Immunology,
Medical College of Virginia at Virginia Commonwealth University,
Richmond, Virginia 23298-0678
Received 27 April 2001/Accepted 18 July 2001
In the Lyme disease spirochetes, both the ospE and
vlsE gene families have been demonstrated to undergo
sequence variation during infection. To further investigate the
mechanisms associated with the generation of vls variation,
single-nucleotide polymorphism and subsequent DNA sequence analyses
were performed on the vlsE gene and its paralog, BBJ51, a
related gene with a frameshift mutation. These analyses focused on a
series of postinfection clonal populations obtained from mice infected
with Borrelia burgdorferi B31MIpc or its clonal derivative,
B31MIc53. vlsE, but not BBJ51, was found to undergo
sequence changes during infection. Consistent with that reported
previously (J.-R. Zhang et al., Cell 89:275-285, 1997) many of
the sequence changes appear to have arisen through gene conversion
events and to be localized to the variable regions of vlsE.
However, analysis of the vlsE nucleotide sequences revealed that some sequence changes were the result of point mutations, as these
changes did not have potential contributing sources in the
vls cassettes. To determine if sequence changes
accumulate in vlsE over long-term infection, the
vlsE genes of clonal populations recovered after 7 months
of infection in mice were analyzed. While new sequence changes
developed, a significant number of these changes resulted in the
restoration of the vlsE sequence of the original infecting
clone. In addition, we noted that some positions within the variable
regions (VR) are stable even though the cassettes possess residues that
could contribute to sequence variation through gene conversion. These
analyses suggest that the total number of amino acid sequence changes
that can be maintained by VlsE levels off during infection. In summary,
in this report we demonstrate that the development of point mutations
serves as a second mechanism by which vlsE sequence
variation can be generated and that the capacity for vlsE
variation, while still significant, is less than previously postulated.
0021-9193/01/$04.00+0 DOI: 10.1128/JB.183.20.5855-5861.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Evidence for the Contribution of Point Mutations to
vlsE Variation and for Apparent Constraints on the Net
Accumulation of Sequence Changes in vlsE during Infection
with Lyme Disease Spirochetes

*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298-0678. Phone: (804) 828-3779. Fax: (804) 828-9946. E-mail:
rmarconi{at}hsc.vcu.edu.
Present address: Molecular Urology and Therapeutics Program,
Department of Urology and Winship Cancer Institute, Emory University, Atlanta, GA 30322.
This article has been cited by other articles:
| Appl. Environ. Microbiol. | Infect. Immun. | Eukaryot. Cell |
|---|---|---|
| Mol. Cell. Biol. | J. Virol. | Microbiol. Mol. Biol. Rev. |
| ALL ASM JOURNALS |