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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Apr 28

PMID 20422019

Citations 10

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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Influence of Streptococcus pneumoniae Within-Strain Population Diversity on Virulence and Pathogenesis.

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Rapid in vivo detection of isoniazid-sensitive Mycobacterium tuberculosis by breath test.

Choi S, Maiga M, Maiga M, Atudorei V, Sharp Z, Bishai W Nat Commun. 2014; 5:4989.

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Organ pathology in the absence of bacteria?.

Jones C, Niederweis M J Infect Dis. 2013; 209(6):971.

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Low dose aerosol fitness at the innate phase of murine infection better predicts virulence amongst clinical strains of Mycobacterium tuberculosis.

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