Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts

19-POS Board 19 High Resolution Snapshot of Genetic Diversity within Mycobacterium Tuberculosis in a Region of High HIV Co-Infection Anastasia Koch 1 , Daniela Brites 2 , Joanna Evans 3 , Ronnet Seldon 3 , Tolu Oni 4 , Mark P. Nicol 5 , Digby F. Warner 3 , Valerie Mizrahi 3 , David Harris 6 , Julian Parkhill 6 , Sebastien Gagneux 2 , Darren P. Martin 7 , Robert J. Wilkinson 1,8 . 1 Institute of Infectious Disease & Molecular Medicine, University of Cape Town, South Africa, 2 Swiss Tropical and Public Health Institute, University of Basel, Switzerland, 3 Institute of Infectious Disease & Molecular Medicine and Division of Medical Microbiology, University of Cape Town, South Africa, 4 School of Public Health and Family Medicine, University of Cape Town, South Africa, 5 Division of Medical Microbiology, University of Cape Town, South Africa, 6 Wellcome Trust Sanger Institute, Cambridge, United Kingdom, 7 Department of Integrative Biomedical Sciences, University of Cape Town, South Africa, 8 The Francis Crick Institute, London, United Kingdom. Infection with HIV greatly increases the risk of becoming infected with tuberculosis (TB) even before a decrease in CD4+ T-cell numbers, and co-infection leads to acceleration of both diseases. The complexity of the biological interactions between HIV, Mycobacterium tuberculosis (Mtb) and the human immune system are incompletely understood. Our study was designed to investigate differences in genetic microdiversity of Mtb samples from HIV-infected and HIV-uninfected patients. Whole genome sequencing (WGS) data for 190 strains (with almost equal numbers isolated from HIV-infected and HIV-uninfected individuals) was generated. No profound differences were observed in clustering patterns, or in overall genetic diversity between Mtb strains isolated from HIV-infected or HIV-uninfected individuals. Lineage 2 Mtb strains isolated from HIV-infected individuals contained a higher number of SNPs in epitope encoding genes than those isolated from HIV-uninfected individuals. However, a similar trend was observed for essential genes, therefore definitive inferences about antigenic variation could not be drawn from SNP counts. Formal analysis of selection is underway using models available as part of the HyPhy package. Preliminary results from a MEDS analysis indicate differential selective pressures on genes important for host-pathogen interactions between Mtb strains isolated from HIV-uninfected or HIV-infected groups. Recombination – which can confound detection of selection – was evaluated the Recombination Detection Package, and found to be minimal. The impact of HIV on the TB rates, particularly in sub- Saharan Africa, has been devastating. These data may elucidate pathways that are important for the biological interactions between these two diseases and the human immune system. Moreover, selection tests as well as recombination analyses have been infrequently reported for Mtb, and are also therefore novel.

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