Mycobacterium tuberculosisにおける抗生物質耐性の競争力のあるコストについて
Sebastien Gagneux1, Clara Davis Long, Peter M Small
1Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 94305, USA. sgagneux@systemsbiology.org
Science (New York, N.Y.)
|July 1, 2006
まとめ
多剤耐性結核菌株は,フィットネスコストなしで出現し,流行の予測に挑戦することができます. 特定の突然変異と宿主遺伝子は,Mycobacterium tuberculosisの耐性コストに影響を与える.
科学分野:
- 微生物学 微生物学とは
- エピデミオロジー エピデミオロジー
- 遺伝学 遺伝学とは
背景:
- 数学的モデルによると,多剤耐性結核 (MDR-TB) の将来は,薬剤耐性のフィットネスコストに依存している.
- このフィットネスコストを理解することは,MDR-TBの流行を予測し,制御するために不可欠です.
研究 の 目的:
- 薬剤耐性変異とMycobacterium tuberculosisにおけるフィットネスコストとの関係を調査する.
- 臨床MDR-TB単離体が耐性に関連したフィットネス欠陥を示すかどうかを判断する.
主な方法:
- リファムシン耐性を持つMycobacterium tuberculosis変異体の実験室派生. リファムシン耐性を持つMycobacterium tuberculosis変異体の実験室派生. リファムシン耐性を持つMycobacterium tuberculosis変異体の実験室派生. リファムシン耐性を持つMycobacterium tuberculosis変異体の実験室派生. リファムシン耐性を持つMycobacterium tuberculosis変異体の実験室派生.
- 耐性菌株と感受性菌株を比較した競争力試験.
- 耐性変異と遺伝子背景の分析,実験室および臨床単離.
主要な成果:
- 実験室の変異体におけるリファンピン耐性は,競争力のあるフィットネスコストと一貫して関連しています.
- このフィットネスコストの大きさは,特定の耐性変異とMycobacterium tuberculosis菌株の遺伝的背景によって異なります.
- 長期にわたる患者の治療は,目に見える健康欠陥のないMDR-TB菌株につながる可能性があります.
- 臨床的孤立種は,低コストまたは無コストの耐性変異を頻繁に持ち,その進化的優位性を示唆しています.
結論:
- Mycobacterium tuberculosisの薬剤耐性は,いくつかの予測に反して,常にフィットネスコストを課すわけではありません.
- MDR-TBの進化は,特定の変異と宿主因によって影響を受け,フィットネス上の罰則を最小限に抑えるか排除することができます.
- 低コストまたは無コストの耐性突然変異の臨床環境での流行は,進行中のMDR-TBの流行におけるそれらの重要な役割を強調しています.
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