Antimicrobial peptides derived from Nemuri induce ribosomal condensation to inhibit translation

Antibiotic resistance is a global health threat requiring antimicrobials with alternative modes of action. Growing evidence indicates that bacteria organize key intracellular processes through biomolecular condensates and other forms of spatial organization, yet whether such spatial organization can be exploited as an antimicrobial target remains unclear. Here, we identify intrinsically disordered antimicrobial peptides, generated from the Drosophila sleep-inducing protein Nemuri, that inhibit bacterial growth by targeting ribosomal organization. Mechanistically, these peptides enter bacterial cells without overt membrane disruption and accumulate in ribosome-rich regions, where they bind broadly to RNA and ribosomal surfaces through multivalent interactions. This engagement remodels ribosome-rich regions into condensates with reduced ribosomal mobility, thereby suppressing global protein synthesis and distinguishing these peptides from canonical site-specific ribosome-targeting antibiotics. Furthermore, Nemuri-derived peptides exhibit broad-spectrum antimicrobial activity, including activity against drug-resistant pathogens, with low cytotoxicity toward Drosophila and mammalian cells. Together, our findings identify the organization and material dynamics of bacterial ribosomes as a biophysical vulnerability that can be exploited by antimicrobial peptides, revealing how a naturally evolved metazoan host-defense system turns intracellular organization itself into an antibacterial target.

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Publication Details

Journal
Nature Communications
Published
2026-10-29
DOI
https://doi.org/10.1038/s41467-026-78960-5
Primary Topic
Antimicrobial Peptides and Activities
Type
article
Field-Weighted Citation Impact
0.00

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article

Antimicrobial peptides derived from Nemuri induce ribosomal condensation to inhibit translation

Suguru Nishinami, Hiroyuki Kumeta, Yūko Fujioka, Masato Machida et al.
3 links
Nature Communications
Antimicrobial Peptides and Activities
article

Antimicrobial peptides derived from Nemuri induce ribosomal condensation to inhibit translation

Suguru Nishinami, Hiroyuki Kumeta, Yūko Fujioka, Masato Machida, Ryohei Sasaki, Natsumi Ageta‐Ishihara, Hiroka Sugai, Tomokazu Ohishi, Shinji Kajimoto, Hikari Yoshitane, Tatsuya Niwa, Kenji Iwasaki, Masayuki Igarashi, Amita Sehgal, Nobuo N. Noda, Yuta Otobe, Yuta Ogasawara, Yoshimasa Ishizaki, Yoshikazu Tanaka, Takakazu Nakabayashi, Hirofumi Toda, Takeshi Yokoyama, Moynul Hasan, Tomohiro Inui, Hiroto Otsuki, Mohammed Abdelaziz
article en

Abstract

Antibiotic resistance is a global health threat requiring antimicrobials with alternative modes of action. Growing evidence indicates that bacteria organize key intracellular processes through biomolecular condensates and other forms of spatial organization, yet whether such spatial organization can be exploited as an antimicrobial target remains unclear. Here, we identify intrinsically disordered antimicrobial peptides, generated from the Drosophila sleep-inducing protein Nemuri, that inhibit bacterial growth by targeting ribosomal organization. Mechanistically, these peptides enter bacterial cells without overt membrane disruption and accumulate in ribosome-rich regions, where they bind broadly to RNA and ribosomal surfaces through multivalent interactions. This engagement remodels ribosome-rich regions into condensates with reduced ribosomal mobility, thereby suppressing global protein synthesis and distinguishing these peptides from canonical site-specific ribosome-targeting antibiotics. Furthermore, Nemuri-derived peptides exhibit broad-spectrum antimicrobial activity, including activity against drug-resistant pathogens, with low cytotoxicity toward Drosophila and mammalian cells. Together, our findings identify the organization and material dynamics of bacterial ribosomes as a biophysical vulnerability that can be exploited by antimicrobial peptides, revealing how a naturally evolved metazoan host-defense system turns intracellular organization itself into an antibacterial target.

Nature CommunicationsVol. 17(1)
Toho University (JP), Howard Hughes Medical Institute (US), University of Tsukuba (JP), Tohoku University (JP), Hokkaido University (JP), Tokyo Metropolitan Institute of Medical Science (JP), Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA) (JP), International Institute for Integrative Sleep Medicine, University of Tsukuba (JP), Advanced Research Center for Innovations in Next-Generation Medicine, Organization for Advanced Studies, Tohoku University (JP), Cell Biology Center (JP), Institute for Genetic Medicine, Hokkaido University (JP), Institute of Integrated Research, Institute of Science Tokyo (JP), The University of Tokyo (JP), University of Pennsylvania (US)
Takeda Science Foundation, Japan Agency for Medical Research and Development, Ministry of Education, Culture, Sports, Science and Technology, Inamori Foundation, Mitsubishi Foundation, Hokkaido University, University of Tsukuba, Japan Society for the Promotion of Science, Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Precursory Research for Embryonic Science and Technology
Good health and well-being
Openalex Percentile: Top 14%
Antimicrobial Peptides and Activities
DOIOpen Access PDFOpenAlex
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