Hypervirulent mutant of Mycobacterium tuberculosis resulting from disruption of the mce1 operon

Nobuyuki Shimono, Lisa Morici, Nicola Casali, Sally Cantrell, Ben Sidders, Sabine Ehrt, Lee W. Riley

研究成果: Contribution to journalArticle査読

153 被引用数 (Scopus)

抄録

An estimated one-third of the world's population is latently infected with Mycobacterium tuberculosis, the etiologic agent of tuberculosis. Here, we demonstrate that, unlike wild-type M. tuberculosis, a strain of M. tuberculosis disrupted in the mce1 operon was unable to enter a stable persistent state of infection in mouse lungs. Instead, the mutant continued to replicate and killed the mice more rapidly than did the wild-type strain. Histological examination of mouse lungs infected with the mutant strain revealed diffusely organized granulomas with aberrant inflammatory cell migration. Murine macrophages infected ex vivo with the mutant strain were reduced in their ability to produce tumor necrosis factor α, IL-6, monocyte chemoattractant protein 1, and nitric oxide (NO), but not IL-4. The mce1 mutant strain complemented with the mce1 genes stimulated tumor necrosis factor α and NO production by murine macrophages at levels stimulated by the wild-type strain. These observations indicate that the mce1 operon mutant is unable to stimulate T helper 1-type immunity in mice. The hypervirulence of the mutant strain may have resulted from its inability to stimulate a proinflammatory response that would otherwise induce organized granuloma formation and control the infection without killing the organism. The mce1 operon of M. tuberculosis may be involved in modulating the host inflammatory response in such a way that the bacterium can enter a persistent state without being eliminated or causing disease in the host.

本文言語英語
ページ(範囲)15918-15923
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
100
26
DOI
出版ステータス出版済み - 12 23 2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • General

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