牛由来の細菌がMRSA治療に効果(Bacteria from cows show promising results in treating MRSA infections)

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2025-07-17 コペンハーゲン大学(UCPH)

牛由来の細菌がMRSA治療に効果(Bacteria from cows show promising results in treating MRSA infections)
“With our mapping, we can identify which signaling molecules are most effective against MRSA,” says researcher behind new study. Illustration: William Brøns Petersen

コペンハーゲン大学の研究チームは、ウシなどの動物が持つ細菌由来の「シグナリング分子(quorum sensing 信号分子)」が、MRSA(メチシリン耐性黄色ブドウ球菌)感染治療に効果的であることを動物モデルで実証した。ウシ由来のStaphylococcus simulansが生成する分子は、MRSAの細胞間コミュニケーションを攪乱し、マウスの皮膚感染を単回投与で抗生物質軟膏と同等に治癒させた。また、細菌に対する耐性が実験条件下で15日間観察しても発生しなかった。このアプローチは細菌殺菌ではなくコミュニケーション阻害による「攻撃の抑制」を目的としており、耐性対策として有望である。

<関連情報>

常在菌と病原性ブドウ球菌のクオラムセンシング相互作用ネットワークのマッピング Mapping of quorum sensing interaction network of commensal and pathogenic staphylococci

Bengt H. Gless, Benjamin S. Sereika-Bejder, Iben Jensen, Martin S. Bojer, Katerina Tsiko, Sabrina H. Schmied, Ludovica Vitolo, Bruno Toledo-Silva, Sarne De Vliegher, Hanne Ingmer, Christian A. Olsen
mBio  Published:16 July 2025
DOI:https://doi.org/10.1128/mbio.00967-25

ABSTRACT

Staphylococci utilize secreted autoinducing peptides (AIPs) to regulate group behavior through a process called quorum sensing (QS). For pathogenic staphylococci, such as Staphylococcus aureus, QS regulates the expression of major virulence factors, and QS inhibition has been proposed as an alternative to antibiotics for the treatment of infections with methicillin-resistant S. aureus (MRSA). Here, we surveyed the interaction map between QS systems of the pathogens S. aureus, Staphylococcus epidermidis, and Staphylococcus lugdunensis and all the currently known staphylococcal AIPs, covering 21 different species. We identified six of these ribosomally synthesized and post-translationally modified peptides (RiPPs) in this study and compiled the full collection of AIPs by chemical synthesis. The resulting mapping provided 280 QS interactions that were divided into human- and animal-associated staphylococci, showing substantial differences in inhibitory potencies between the groups. AIPs of the bovine-associated species Staphylococcus simulans displayed potential as QS inhibitors toward the investigated strains and were therefore chosen as a starting point for a structure-activity relationship study. This study provides insights into the requirements for QS interference, yielding the most potent inhibitors reported to date for S. epidermidis and S. lugdunensis. Furthermore, we tested an S. simulans AIP as an anti-virulence agent in an assay to assess the risk of acquired suppression of the inhibitory effect, and we established an assay set-up to successfully monitor agr deactivation of virulent MRSA by the QS inhibitor. Finally, a peptide was shown to attenuate skin infection caused by MRSA in a mouse model. Our results reveal a complex network of staphylococcal interactions and provide further impetus for the investigation of QS modulation in the targeting of antibiotic-resistant pathogens.

医療・健康
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