The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models

It has been hypothesized that the virulence of lab-passaged Mycobacterium tuberculosis and recombinant M. tuberculosis mutants might be reduced due to multiple in vitro passages, and that virulence might be augmented by passage of these strains through mice before quantitative virulence testing in t...

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Veröffentlicht in:PloS one 2010-04, Vol.5 (4), p.e10289
Hauptverfasser: Converse, Paul J, Eisenach, Kathleen D, Theus, Sue A, Nuermberger, Eric L, Tyagi, Sandeep, Ly, Lan H, Geiman, Deborah E, Guo, Haidan, Nolan, Scott T, Akar, Nicole C, Klinkenberg, Lee G, Gupta, Radhika, Lun, Shichun, Karakousis, Petros C, Lamichhane, Gyanu, McMurray, David N, Grosset, Jacques H, Bishai, William R
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container_issue 4
container_start_page e10289
container_title PloS one
container_volume 5
creator Converse, Paul J
Eisenach, Kathleen D
Theus, Sue A
Nuermberger, Eric L
Tyagi, Sandeep
Ly, Lan H
Geiman, Deborah E
Guo, Haidan
Nolan, Scott T
Akar, Nicole C
Klinkenberg, Lee G
Gupta, Radhika
Lun, Shichun
Karakousis, Petros C
Lamichhane, Gyanu
McMurray, David N
Grosset, Jacques H
Bishai, William R
description It has been hypothesized that the virulence of lab-passaged Mycobacterium tuberculosis and recombinant M. tuberculosis mutants might be reduced due to multiple in vitro passages, and that virulence might be augmented by passage of these strains through mice before quantitative virulence testing in the mouse or guinea pig aerosol models. By testing three M. tuberculosis H37Rv samples, one deletion mutant, and one recent clinical isolate for survival by the quantitative organ CFU counting method in mouse or guinea pig aerosol or intravenous infection models, we could discern no increase in bacterial fitness as a result of passaging of M. tuberculosis strains in mice prior to quantitative virulence testing in two animal models. Surface lipid expression as assessed by neutral red staining and thin-layer chromatography for PDIM analysis also failed to identify virulence correlates. These results indicate that animal passaging of M. tuberculosis strains prior to quantitative virulence testing in mouse or guinea pig models does not enhance or restore potency to strains that may have lost virulence due to in vitro passaging. It is critical to verify virulence of parental strains before genetic manipulations are undertaken and comparisons are made.
doi_str_mv 10.1371/journal.pone.0010289
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subjects Aerosol models
Aerosols
Analysis
Animal models
Animals
Bacteria
Bacteriological Techniques - standards
Cattle
Chromatography
Deletion mutant
Drug resistance
Fitness
Genetic engineering
Genetic Fitness
Guinea Pigs
Infectious Diseases
Infectious Diseases/Bacterial Infections
Infectious Diseases/Respiratory Infections
Intravenous administration
Laboratories
Lipids
Lipids - analysis
Medicine
Mice
Microbiology/Cellular Microbiology and Pathogenesis
Microbiology/Microbial Growth and Development
Models, Animal
Mortality
Mutagenesis
Mutants
Mycobacterium tuberculosis
Mycobacterium tuberculosis - cytology
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - pathogenicity
Nobel prizes
Pathogenesis
Permeability
Reproductive fitness
Research Design - standards
Sequence Deletion
Serial Passage
Strains (organisms)
Swine
Thin layer chromatography
Tuberculosis
Tuberculosis - microbiology
Virulence
Virulence (Microbiology)
title The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models
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