Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

BMC Genomics

Research Article

Arnab Pain¹  Theolis Barbosa Bessa²  Erivelton de Oliveira Sousa²  Keertan Dheda³  David Moore⁴  Francesc Coll⁴  Martin L. Hibberd⁴  Susana Campino⁴  Jody E. Phelan⁴  Ruth McNerney⁴  Taane G. Clark⁵  Louis Grandjean⁶  Rumina Hasan⁷  Zahra Hasan⁷  Paul D. van Helden⁸  Rob Warren⁸  Elizabeth M. Streicher⁸  Nicolaas C. Gey van Pittius⁸  Samantha L. Sampson⁸  Judith R. Glynn⁹  Amelia C. Crampin^1,10  Miguel Viveiros^1,11  Richard M. Anthony^1,12  Indra Bergval^1,12  Patricia Sheen^1,13  Stefan Panaiotov^1,14  Anabela Miranda^1,15  Adriana Alves^1,15  Joao Perdigao^1,16  Isabel Portugal^1,16 

[1] Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia;Centro de Pesquisas Goncalo Moniz, Fundacao Oswaldo Cruz Bahia R, Salvador, Bahia, Brazil;Department of Medicine, Lung Infection and Immunity Unit, Division of Pulmonology & UCT Lung Institute, University of Cape Town, Cape Town, Western Cape, South Africa;Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, Western Cape, South Africa;Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, WC1E 7HT, London, UK;Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, WC1E 7HT, London, UK;Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, WC1E 7HT, London, UK;Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, WC1E 7HT, London, UK;Laboratorio de Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru;Department of Pathology and Laboratory Medicine, The Aga Khan University, Stadium Road, Karachi, Pakistan;Department of Science and Technology and National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, and Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa;Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, WC1E 7HT, London, UK;Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, WC1E 7HT, London, UK;Karonga Prevention Study, Lilongwe, Malawi;Grupo de Micobactérias, Unidade de Microbiologia Médica, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa (IHMT/UNL), Lisbon, Portugal;KIT Biomedical Research, Royal Tropical Institute, Amsterdam, Netherlands;Laboratorio de Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru;National Center of Infectious and Parasitic Diseases, 1504, Sofia, Bulgaria;National Mycobacterium Reference Laboratory, Porto, Portugal;Universidade de Lisboa, Lisbon, Portugal;

关键词: Tuberculosis;    Major Histocompatibility Complex Molecule;    Mycobacterium Tuberculosis Complex;    Tuberculosis Lineage;    Variable Selective Pressure;   

DOI  :  10.1186/s12864-016-2467-y

 received in 2015-11-12, accepted in 2016-02-12,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundApproximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate (PPE) signature motifs. They are hypothesised to be important virulence factors involved with host-pathogen interactions, but their high genetic variability and complexity of analysis means they are typically disregarded in genome studies.ResultsTo elucidate the structure of these genes, 518 genomes from a diverse international collection of clinical isolates were de novo assembled. A further 21 reference M. tuberculosis complex genomes and long read sequence data were used to validate the approach. SNP analysis revealed that variation in the majority of the 168 pe/ppe genes studied was consistent with lineage. Several recombination hotspots were identified, notably pe_pgrs3 and pe_pgrs17. Evidence of positive selection was revealed in 65 pe/ppe genes, including epitopes potentially binding to major histocompatibility complex molecules.ConclusionsThis, the first comprehensive study of the pe and ppe genes, provides important insight into M. tuberculosis diversity and has significant implications for vaccine development.

【 授权许可】

CC BY   
© Phelan et al. 2016