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J Med Microbiol 57 (2008), 164-170; DOI: 10.1099/jmm.0.47454-0
© 2008 Society for General Microbiology
ISSN 1473-5644

Mycobacterium tuberculosis strains disrupted in mce3 and mce4 operons are attenuated in mice

Ryan H. Senaratne1, Ben Sidders1,2,3,{dagger}, Patricia Sequeira1,{dagger}, Grainne Saunders2, Kathleen Dunphy1, Olivera Marjanovic1, J. Rachel Reader4, Patricia Lima1, Stephen Chan1, Sharon Kendall3, Johnjoe McFadden2 and Lee W. Riley1

1 School of Public Health, University of California, Berkeley, CA 94720, USA

2 School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK

3 Department of Pathology and Infectious Disease, Royal Veterinary College, Royal College Street, London NW1 0TU, UK

4 Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA

Correspondence
Lee W. Riley
lwriley{at}berkeley.edu

Received 16 June 2007
Accepted 6 October 2007

The Mycobacterium tuberculosis genome contains four copies of an operon called mce (mce1–4). Previously we reported that M. tuberculosis disrupted in the mce1 operon is more virulent than wild-type M. tuberculosis in mice. We generated single deletion mutants in mce3 ({Delta}mce3) and mce4 ({Delta}mce4) operons and a double deletion mutant ({Delta}mce3/4). Similar doubling times and growth characteristics were observed for all mutants and the wild-type (parent) M. tuberculosis H37Rv strain in culture and in macrophages. In addition, similar bacterial burdens were detected in organs from mice infected with {Delta}mce3 and the parent strain. However, the bacterial burdens of mice infected with {Delta}mce4 and {Delta}mce 3/4 were less than those of mice infected with the parent strain. The median survival times of mice infected with wild-type M. tuberculosis, {Delta}mce3, {Delta}mce4 and {Delta}mce3/4 were 40.5, 46, 58 and 62 weeks, respectively. Histopathological examination of lungs at 15 weeks post-infection showed that the extent of the lung lesions was less prominent in mice infected with {Delta}mce4 and {Delta}mce 3/4 mutants than in mice infected with the other two strains. These observations suggest that the mce3 and mce4 operons have a role distinct from that of mce1 for in vivo survival of M. tuberculosis.

Abbreviations: H&E, haematoxylin and eosin; p.i., post-infection; WT, wild-type.

{dagger}These authors contributed equally to this work.






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