細菌の「遺伝子運び屋」、プラスミドが持つ「生存戦略」を発見~薬剤耐性拡散のパターンが明らかに~

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2026-01-23 東京大学

本研究は、細菌間で遺伝子を運ぶ接合伝達性プラスミドが、異なる「生存戦略」を進化させてきたことを明らかにした。DNA配列の網羅解析により、多様な細菌に広く伝播できる広宿主域プラスミドは、自身の遺伝子発現を抑えて宿主への負担を軽減する「ステルス戦略」をとる一方、限られた宿主に伝播する狭宿主域プラスミドは、宿主の防御機構を操作・阻害する「操作戦略」をとることが示された。さらに、薬剤耐性遺伝子はまずステルス戦略型プラスミドによって初期拡散され、その後に他のプラスミドが二次拡散を担う傾向があることを発見し、「ステルス・ファースト」モデルを提唱した。本成果は、薬剤耐性遺伝子拡散の段階を把握する指標となり、将来的な拡散防止戦略の構築に貢献すると期待される。

細菌の「遺伝子運び屋」、プラスミドが持つ「生存戦略」を発見~薬剤耐性拡散のパターンが明らかに~
提唱した接合伝達性プラスミドの生存戦略とそれらの宿主域・薬剤耐性伝播との関係

<関連情報>

宿主域と抗生物質耐性の伝播は、接合性プラスミドの異なる生存戦略によって形作られる Host range and antibiotic resistance dissemination are shaped by distinct survival strategies of conjugative plasmids

Ryuichi Ono ,Naoki Konno ,Yuki Nishimura ,Chikara Furusawa
Nucleic Acids Research  Published:23 January 2026
DOI:https://doi.org/10.1093/nar/gkaf1479

Abstract

Horizontal gene transfer is a major driver of bacterial evolution and the global dissemination of antibiotic resistance genes (ARGs). Conjugative plasmids play a crucial role in ARG spread across hosts within their host range, yet the genetic and functional determinants shaping plasmid host range remain poorly understood. Here, we systematically analyzed the gene content of conjugative/mobilizable plasmids derived from Enterobacterales from public databases and found that two distinct survival strategies were enriched in different host-range groups: a “stealth” strategy, which actively represses its own transcription by employing a global regulator hns, was particularly enriched in broad-host-range plasmids, whereas a “manipulative” strategy, which promotes its establishment by manipulating host machineries including SOS response and defense systems, was more common in narrow-host-range plasmids. Plasmids employing either strategy constituted the majority of conjugative plasmids analyzed, and accumulated significantly more ARGs than plasmids with neither strategy. Our data further suggested that stealth plasmids facilitate the acquisition of emerging ARGs, while manipulative plasmids amplify the copy number of established ARGs. This “stealth-first” model successfully recapitulated historical ARG dissemination patterns. These findings provide critical insights into the relationship between plasmid survival strategies and host range, advancing our understanding of the global patterns underlying plasmid-mediated ARG transmission.

細胞遺伝子工学
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