Surface display of a massively variable lipoprotein by a Legionella diversity-generating retroelement

Surface display of a massively variable lipoprotein by a Legionella diversity-generating retroelement

Diversity-generating retroelements (DGRs) are a unique family of retroelements that confer selective advantages to their hosts by facilitating localized DNA sequence evolution through a specialized error-prone reverse transcription process. We characterized a DGR in Legionella pneumophila , an oppor...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 20; pp. 8212 - 8217
Main Authors: Arambula, Diego, Wong, Wenge, Medhekar, Bob A., Guo, Huatao, Gingery, Mari, Czornyj, Elizabeth, Liu, Minghsun, Dey, Sanghamitra, Ghosh, Partho, Miller, Jeff F.
Format: Journal Article
Language:English
Published: United States National Academy of Sciences 14-05-2013
National Acad Sciences
Subjects:
Bacterial proteins
Bacterial Proteins - chemistry
Bacteriophages
Base Sequence
Bioinformatics
Biological Sciences
Cell Membrane - metabolism
Deoxyribonucleic acid
DNA
Gene expression
Genes
Genomic Islands
Genomics
Gram-negative bacteria
Homing
Legionella pneumophila
Legionella pneumophila - metabolism
Lipoproteins
Lipoproteins - chemistry
Molecular Sequence Data
Mutagenesis
Open Reading Frames
Protein Structure, Tertiary
Proteins
Retroelements
Retrotransposons
Secretion
Sequence Analysis, DNA
Surface Properties
Virulence
accelerated evolution
bacterial surface display
TAT
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Summary:Diversity-generating retroelements (DGRs) are a unique family of retroelements that confer selective advantages to their hosts by facilitating localized DNA sequence evolution through a specialized error-prone reverse transcription process. We characterized a DGR in Legionella pneumophila , an opportunistic human pathogen that causes Legionnaires disease. The L. pneumophila DGR is found within a horizontally acquired genomic island, and it can theoretically generate 10 ²⁶ unique nucleotide sequences in its target gene, legionella determinent target A (ldtA), creating a repertoire of 10 ¹⁹ distinct proteins. Expression of the L. pneumophila DGR resulted in transfer of DNA sequence information from a template repeat to a variable repeat (VR) accompanied by adenine-specific mutagenesis of progeny VRs at the 3′end of ldtA . ldtA encodes a twin-arginine translocated lipoprotein that is anchored in the outer leaflet of the outer membrane, with its C-terminal variable region surface exposed. Related DGRs were identified in L. pneumophila clinical isolates that encode unique target proteins with homologous VRs, demonstrating the adaptability of DGR components. This work characterizes a DGR that diversifies a bacterial protein and confirms the hypothesis that DGR-mediated mutagenic homing occurs through a conserved mechanism. Comparative bioinformatics predicts that surface display of massively variable proteins is a defining feature of a subset of bacterial DGRs.
Bibliography:http://dx.doi.org/10.1073/pnas.1301366110
Author contributions: D.A., B.A.M., H.G., P.G., and J.F.M. designed research; D.A., W.W., H.G., S.D., and P.G. performed research; M.G., E.C., and M.L. contributed new reagents/analytic tools; D.A., B.A.M., H.G., M.G., E.C., M.L., S.D., P.G., and J.F.M. analyzed data; and D.A., H.G., M.L., P.G., and J.F.M. wrote the paper.
Edited† by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved April 1, 2013 (received for review January 22, 2013)
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1301366110