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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts
90
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.