Annotated Genome Sequences of 16 Lineage 4 Mycobacterium tuberculosis Strains from Guatemala.

Abstract

Whole-genome sequencing has resulted in new insights into the phylogeography of Mycobacterium tuberculosis However, only limited genomic data are available from M. tuberculosis strains in Guatemala. Here we report 16 complete genomes of clinical strains belonging to the Euro-American lineage 4, the most common lineage found in Guatemala and Central America.

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Citation

Published Version (Please cite this version)

10.1128/genomea.00024-18

Publication Info

Saelens, Joseph W, Dalia Lau-Bonilla, Anneliese Moller, Ana M Xet-Mull, Narda Medina, Brenda Guzmán, Maylena Calderón, Raúl Herrera, et al. (2018). Annotated Genome Sequences of 16 Lineage 4 Mycobacterium tuberculosis Strains from Guatemala. Genome announcements, 6(7). pp. e00024–e00018. 10.1128/genomea.00024-18 Retrieved from https://hdl.handle.net/10161/26264.

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Scholars@Duke

Stout

Jason Eric Stout

Professor of Medicine

My research focuses on the epidemiology, natural history, and treatment of tuberculosis and nontuberculous mycobacterial infections. I am also interested in the impact of HIV infection on mycobacterial infection and disease, and in examining health disparities as they relate to infectious diseases, particularly in immigrant populations.

Tobin

David M. Tobin

Professor of Molecular Genetics and Microbiology

Tuberculosis: Mycobacterial Pathogenesis and Host Susceptibility

Tuberculosis kills 1.5 million people annually. Our laboratory aims to understand the intricate interplay between mycobacteria and their hosts using a combination of model organism genetics, human genetics, pharmacology and high-resolution microscopy. By identifying key pathways utilized by the infecting bacteria and the host innate immune system, we hope to discover new therapeutic targets and interventions to combat this enduringly destructive disease.

Using a Mycobacterium/zebrafish model, we have identified new host susceptibility loci for tuberculosis. Zebrafish are natural hosts to Mycobacterium marinum, the closest relative of the Mycobacterium tuberculosis complex. Because zebrafish embryos and larvae are optically transparent, we are able to visualize the complex details of mycobacterial pathogenesis in whole, live animals. The facile genetics of the zebrafish allow us to map and positionally clone affected host susceptibility genes. In addition, zebrafish larvae are remarkably permeable to small molecules, providing a platform for whole-animal pharmacological manipulation of specific host immune responses.

We have identified novel pathways that modulate susceptibility to tuberculosis. We have shown that genes identified in the zebrafish model are also important in human tuberculosis. We find robust associations of human variants in a specific eicosanoid pathway with susceptibility to both tuberculosis and leprosy.

We have active collaborations in both Vietnam and Guatemala. In Guatemala, we are working with the Clínica Familiar Luis Angel García and the Asociación de Salud Integral to support projects involving HIV-infected patients and to understand the dynamics of TB transmission in Central America.


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