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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Mycobacterium tuberculosis strains with the Beijing genotype demonstrate variability in virulence associated with transmission
Tuberculosis, Volume 90, No. 5, Year 2010
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Description
Phylogenetic analysis has shown that Beijing genotype strains can be grouped into at least 7 different sublineages. We aimed to test the hypothesis that the virulence of Beijing genotype strains differed among members of the different sublineages and that the level of virulence correlated with their ability to spread and cause disease. BALB/c mice were infected with Beijing strains representative of the different lineages and of different epidemiological characteristics (transmitted vs. non-transmitted). Survival times, lung pathology, bacterial load and immunology kinetics were evaluated at defined intervals post-infection. Transmissibility was determined by co-housing infected and uninfected mice in close contact for 1-2 months. The results show that mice infected with the highly transmitted Beijing strains began showing mortality 3 weeks post-infection and all had died by 5 weeks, suggesting high virulence phenotypes. In contrast, >80% of mice infected with the non-transmitted strains survived 4 months post-infection, suggesting low virulence phenotypes. Our co-housing transmission model confirmed these virulence phenotypes. Extensive tissue damage and the induction of lower levels of IFNγ and iNOS expression, as well as high but ephemeral TNFα expression were associated with the high virulence phenotype. In contrast, minimal tissue damage and progressive expression of IFNγ and TNFα were associated with the low virulence phenotype. Both virulence phenotypes induced similar levels of IL-4 expression during the early stages of infection after which the high virulence strain induced significantly higher levels of IL-4 expression. In conclusion, this study demonstrates that Beijing genotype strains display a spectrum of virulence phenotypes in mice which mimic their epidemiological characteristics. Both transmissible and non-transmissible strains may exist in the same sublineage. © 2010 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Aguilar L, D.
Mexico, Tlalpan
Instituto Nacional de la Nutrición Salvador Zubiran
Hanekom, Madeleine
South Africa, Cape Town
Stellenbosch University, Faculty of Medicine and Health Sciences
Mata, D.
Mexico, Tlalpan
Instituto Nacional de la Nutrición Salvador Zubiran
Gey van Pittius, Nicolaas Claudius
South Africa, Stellenbosch
Stellenbosch University
Van Helden, Paul D.
South Africa, Stellenbosch
Stellenbosch University
Warren, Robin Mark
South Africa, Stellenbosch
Stellenbosch University
Hernández-Pando, Rogelio E.
Mexico, Tlalpan
Instituto Nacional de la Nutrición Salvador Zubiran
Statistics
Citations: 102
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1016/j.tube.2010.08.004
ISSN:
14729792
Research Areas
Genetics And Genomics