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

Paul J. Converse, Kathleen D. Eisenach, Sue A. Theus, Eric L. Nuermberger, Sandeep Tyagi, Lan H. Ly, Deborah E. Geiman, Haidan Guo, Scott T. Nolan, Nicole C. Akar, Lee G. Klinkenberg, Radhika Gupta, Shichun Lun, Petros C. Karakousis, Gyanu Lamichhane, David N. McMurray, Jacques H. Grosset, William R. Bishai

Research output: Contribution to journalArticle

Abstract

Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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.

Original languageEnglish (US)
Article numbere10292
JournalPloS one
Volume5
Issue number4
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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  • Cite this

    Converse, P. J., Eisenach, K. D., Theus, S. A., Nuermberger, E. L., Tyagi, S., Ly, L. H., Geiman, D. E., Guo, H., Nolan, S. T., Akar, N. C., Klinkenberg, L. G., Gupta, R., Lun, S., Karakousis, P. C., Lamichhane, G., McMurray, D. N., Grosset, J. H., & Bishai, W. R. (2010). The Impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models. PloS one, 5(4), [e10292]. https://doi.org/10.1371/journal.pone.0010289