The Impact of Mouse Passaging of Mycobacterium tuberculosis Strains prior to Virulence Testing in the Mouse and Guinea Pig Aerosol Models

被引：13

作者：

Converse, Paul J. ^{[1
]}

Eisenach, Kathleen D. ^{[2
]}

Theus, Sue A. ^{[2
]}

Nuermberger, Eric L. ^{[1
]}

Tyagi, Sandeep ^{[1
]}

Ly, Lan H. ^{[3
]}

Geiman, Deborah E. ^{[1
]}

Guo, Haidan ^{[1
]}

Nolan, Scott T. ^{[1
]}

Akar, Nicole C. ^{[1
]}

Klinkenberg, Lee G. ^{[1
]}

Gupta, Radhika ^{[1
]}

Lun, Shichun ^{[1
]}

Karakousis, Petros C. ^{[1
]}

Lamichhane, Gyanu ^{[1
]}

McMurray, David N. ^{[3
]}

Grosset, Jacques H. ^{[1
]}

Bishai, William R. ^{[1
]}

机构：

[1] Johns Hopkins Univ, Dept Med, Ctr TB Res, Baltimore, MD 21218 USA

[2] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA

[3] Texas A&M Univ, Dept Microbial & Mol Pathogenesis, College Stn, TX USA

来源：

PLOS ONE | 2010年 / 5卷 / 04期

基金：

美国国家卫生研究院;

关键词：

SIGMA-FACTOR; RESISTANCE; EXPRESSION; RELEVANCE; LIPIDS; MICE;

D O I：

10.1371/journal.pone.0010289

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

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