エフフルスポンプ発現における異質性は,抗生物質耐性細胞の変異を誘発する

Imane El Meouche^1,2, Mary J Dunlop^3,2

¹Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA 02215, USA.

Science (New York, N.Y.)

|November 10, 2018

まとめ

多剤流出ポンプによって引き起こされる暫定的な抗生物質耐性は変異率を増やす可能性がありますこれは一時的な細菌回避戦略が永久的な遺伝的変化と抗生物質耐性につながる可能性があることを示唆しています

科学分野:

微生物学
遺伝学
分子生物学

背景:

抗生物質耐性は公衆衛生上の脅威として増大しています
バクテリアは多剤流出ポンプのようなメカニズムで一時的な耐性を開発することができます.
暫定的な耐性と永続的な遺伝子変異の促進との関連は不明である.

研究の目的:

細菌における一時的な抗生物質耐性が永久的な遺伝的変化を促すかどうかを調査する.
このプロセスにおける AcrAB-TolC マルチドラッグポンプの役割を調べる.

主な方法:

タイムラップ顕微鏡を用いて細菌の行動を観察しました
マルチドラッグポンプAcrAB-TolCとDNAミスマッチ修復遺伝子 MutSの発現を分析した
バクテリア集団における量化された変異頻度

主要な成果:

AcrAB- TolCポンプのより高い発現は,MutS遺伝子のより低い発現と相関する.
AcrAB- TolC発現の上昇は,バクテリアの成長率の低下と関連していました.
AcrAB- TolC発現率が高い細胞では,突然変異の頻度が増加した.

結論:

AcrAB- TolCの発現が増加した一時的な抗生物質抵抗は,自発的な変異を促す可能性があります.
このメカニズムは暫定的な細菌逃避戦略が永久的な抗生物質耐性の進化を促す可能性を示しています

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