抗生物質耐性に対抗する次世代CRISPR遺伝子技術の開発(Next Generation Genetics Technology Developed to Counter the Rise of Antibiotic Resistance)

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2026-02-06 カリフォルニア大学サンディエゴ校(UCSD)

米国カリフォルニア大学サンディエゴ校(UCサンディエゴ)の研究チームは、抗生物質耐性の拡大に対抗する次世代遺伝学技術を開発した。本研究は、細菌集団内で耐性遺伝子がどのように出現・拡散するかを高精度で追跡・制御できる新しいゲノム工学的アプローチを提示するものである。研究チームは、特定の遺伝子配列を精密に編集・解析できる技術を用い、耐性獲得に関与する遺伝子ネットワークを体系的に特定することに成功した。これにより、耐性菌の進化を抑制する標的遺伝子の同定や、新規抗菌戦略の設計が可能になる。成果は、世界的な公衆衛生課題である薬剤耐性問題に対し、予防的かつ根本的な解決策を提供する重要な一歩と位置づけられている。

抗生物質耐性に対抗する次世代CRISPR遺伝子技術の開発(Next Generation Genetics Technology Developed to Counter the Rise of Antibiotic Resistance)

<関連情報>

接合遺伝子ドライブのようなシステムが細菌集団における抗生物質耐性を効率​​的に抑制する A conjugal gene drive-like system efficiently suppresses antibiotic resistance in a bacterial population

Saluja Kaduwal,Elizabeth C. Stuart,Ankush Auradkar,Seth Washabaugh,Justin R. Meyer & Ethan Bier
npj Antimicrobials and Resistance  Published:02 February 2026
DOI:https://doi.org/10.1038/s44259-026-00181-z

Abstract

Antibiotic resistance (AR) is an escalating public health threat, necessitating innovative strategies to control resistant bacterial populations. One promising approach involves engineering genetic elements that can spread within microbial communities to eliminate AR genes. Previously, we developed Pro-Active Genetics (Pro-AG), a CRISPR-based gene-drive-like system capable of reducing AR colony-forming units (CFU) by approximately five logs. Here, we advance this technology by integrating Pro-AG into a conjugative transfer system, enabling efficient dissemination of an anti-AR gene cassette between two bacterial strains. Additionally, we characterize a complementary homology-based deletion (HBD) process, a CRISPR-driven mechanism that precisely removes target DNA sequences flanked by short direct repeats. Our findings reveal that Pro-AG and HBD are differentially influenced by the bacterial RecA pathway and that HBD components can be delivered via plasmids or phages to selectively delete Pro-AG cassettes. This built-in safeguard prevents uncontrolled spread of a gene cassette and mitigates unanticipated side effects. These refinements enhance the efficiency and flexibility of Pro-AG, expanding its potential applications in microbiome engineering, environmental remediation, and clinical interventions aimed at combating antibiotic resistance. More broadly, this work establishes a proof-of-principle for microbiome engineering strategies that could be leveraged to improve health and restore ecological balance.

細胞遺伝子工学
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