Genetic diversity of the Leptospiral immunoglobulin-like (Lig) genes in pathogenic Leptospira spp. |
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| Authors: | Alan JA McBride Gustavo M Cerqueira Marc A Suchard Angela N Moreira Richard L Zuerner Mitermayer G Reis David A Haake Albert I Ko Odir A Dellagostin |
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| Institution: | 1. Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil;2. Centro de Biotecnologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil;3. Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;4. Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;5. Department of Biostatistics, UCLA School of Public Health, Los Angeles, CA, USA;6. National Animal Disease Centre, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa, USA;7. Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA;8. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;9. Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, New York, NY, USA;3. Department of Life Science and Institute of Bioinformatics and Structural Biology, College of Life Science, National Tsing Hua University, Hsin Chu 30013;4. Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33333;5. Institute of Biotechnology, College of Health Sciences, Central Taiwan University of Science and Technology, Taichung 40601;6. Department of Engineering and System Science, College of Nuclear Science, National Tsing Hua University, Hsin Chu 30013, Taiwan;1. Department of Medical Microbiology and Parasitology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia;2. Malaysia Genome Institute, Ministry of Science Technology and Innovation, Bangi, 43600 Kajang, Selangor, Malaysia;3. Department of Biomedical Science, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia;4. Department of Chemical and Materials Engineering, National Central University, Jhong-li, Taoyuan, 32001 Taiwan;5. Department of Botany and Microbiology, King Saud University, Riyadh, 11451, Saudi Arabia;6. Biomaterials in Medicinal Chemistry Laboratory, Department of Natural Products Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai-21, Tamil Nadu, India;7. Department of Agriculture, Food and Environment, University of Pisa, via del Borghetto 80, 56124 Pisa, Italy;8. The BioRobotics Institute, Scuola Superiore Sant’ Anna, Viale Rinaldo Piaggio 34, 56025 Pontedera, Pisa, Italy;9. Muthayammal Centre for Advanced Research, Muthayammal College of Arts and Science, Rasipuram, Namakkal, Tamil Nadu, 637408, India;10. Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia;1. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia;2. Melioidosis Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;3. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;1. Programa de Pós-Graduação em Biotecnologia, Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, RS, Brazil;2. Departamento de Microbiologia e Parasitologia, Instituto de Biologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil |
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| Abstract: | Recent serologic, immunoprotection, and pathogenesis studies identified the Lig proteins as key virulence determinants in interactions of leptospiral pathogens with the mammalian host. We examined the sequence variation and recombination patterns of ligA, ligB, and ligC among 10 pathogenic strains from five Leptospira species. All strains were found to have intact ligB genes and genetic drift accounting for most of the ligB genetic diversity observed. The ligA gene was found exclusively in L. interrogans and L. kirschneri strains, and was created from ligB by a two-step partial gene duplication process. The aminoterminal domain of LigB and the LigA paralog were essentially identical (98.5 ± 0.8% mean identity) in strains with both genes. Like ligB, ligC gene variation also followed phylogenetic patterns, suggesting an early gene duplication event. However, ligC is a pseudogene in several strains, suggesting that LigC is not essential for virulence. Two ligB genes and one ligC gene had mosaic compositions and evidence for recombination events between related Leptospira species was also found for some ligA genes. In conclusion, the results presented here indicate that Lig diversity has important ramifications for the selection of Lig polypeptides for use in diagnosis and as vaccine candidates. This sequence information will aid the identification of highly conserved regions within the Lig proteins and improve upon the performance characteristics of the Lig proteins in diagnostic assays and in subunit vaccine formulations with the potential to confer heterologous protection. |
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