ArticlePloS one2014
Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Fitness costs of Mycobacterium tuberculosis resistant to rifampicin is compensated by rapid Th2 polarization mediated by early and high IL-4 production during mice infection.Scientific reports · 2025Article
- Novel Experimental Mouse Model to Study the Pathogenesis and Therapy ofPathogens (Basel, Switzerland) · 2024Article
- Rifampicin drug resistance and host immunity in tuberculosis: more than meets the eye.Trends in immunology · 2023Review
- A Single Amino Acid Replacement in Penicillin-Binding Protein 2X in Streptococcus pyogenes Significantly Increases Fitness on Subtherapeutic Benzylpenicillin Treatment in a Mouse Model of Necrotizing Myositis.The American journal of pathology · 2020Article
- Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced fromInfection and drug resistance · 2020Article
- Genetic Evolution ofCanadian respiratory journal · 2020Article
- Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- In vitro and in vivo fitness costs associated with Mycobacterium tuberculosis RpoB mutation H526D.Future microbiology · 2017Article
- A Nonsynonymous SNP Catalog of Mycobacterium tuberculosis Virulence Genes and Its Use for Detecting New Potentially Virulent Sublineages.Genome biology and evolution · 2017Article
- Tradeoffs in Introduction Policies for the Anti-Tuberculosis Drug Bedaquiline: A Model-Based Analysis.PLoS medicine · 2016Article
- Epidemiology and Clinical Characteristics of Pediatric Drug-Resistant Tuberculosis in Chongqing, China.PloS one · 2016Article
- CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections.Disease models & mechanisms · 2015Article
- Article
- Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells.PloS one · 2014Article
- Wavelet-domain elastic net for clustering on genomes strains.Genetics and molecular biologyArticle
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Bacterial drug resistance is often associated with a fitness cost. Large outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB have been described that predominately affect persons with HIV infection. We obtained four closely-related Mycobacterium tuberculosis strains (genotype F15/LAM4/KZN) from an outbreak in KwaZulu-Natal (KZN), South Africa, including drug-sensitive, MDR, and XDR clinical isolates. We compared the virulence of these strains in a murine model of aerosol M. tuberculosis infection for four phenotypes: (1) competitive in vivo growth in lung and spleen, (2) non-competitive in vivo growth in lung and spleen, (3) murine survival time, and (4) lung pathology. When mixtures of sensitive, MDR, and XDR KZN strains were aerosolized (competitive model), lung CFUs were similar at 60 days after infection, and spleen CFUs were ordered as follows: sensitive > MDR > XDR. When individual strains were aerosolized (non-competitive model), modest differences in lung and spleen CFUs were observed with the same ordering. C57BL/6, C3H/FeJ, and SCID mice all survived longer after infection with MDR as compared to sensitive strains. SCID mice infected with an XDR strain survived longer than those infected with MDR or sensitive strains. Lung pathology was reduced after XDR TB infection compared to sensitive or MDR TB infection. In summary, increasing degrees of drug resistance were associated with decreasing murine virulence in this collection of KZN strains as measured by all four virulence phenotypes. The predominance of HIV-infected patients in MDR and XDR TB outbreaks may be explained by decreased virulence of these strains in humans.
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