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  • Gu, PengSouthern Medical University, Guangzhou, China (author)

A metabolite from commensal Candida albicans enhances the bactericidal activity of macrophages and protects against sepsis

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • London :Nature Publishing Group,2023
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:hh-51592
  • https://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-51592URI
  • https://doi.org/10.1038/s41423-023-01070-5DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding: The National Natural Science Foundation of China (32271230 and 32071124) to PC; the NIH Grant (P30DK120515) to BS; the National Natural Science Foundation of China (82270581) to YC; the National Key R&D Project of China (2018YFC0115301), the National Natural Science Foundation of China (81974070), the Shenzhen Science and Technology Program (JCYJ20210324131010027) and the Research Foundation of Shenzhen Hospital of Southern Medical University (PT2018GZR10) to WG.
  • The gut microbiome is recognized as a key modulator of sepsis development. However, the contribution of the gut mycobiome to sepsis development is still not fully understood. Here, we demonstrated that the level of Candida albicans was markedly decreased in patients with bacterial sepsis, and the supernatant of Candida albicans culture significantly decreased the bacterial load and improved sepsis symptoms in both cecum ligation and puncture (CLP)-challenged mice and Escherichia coli-challenged pigs. Integrative metabolomics and the genetic engineering of fungi revealed that Candida albicans-derived phenylpyruvate (PPA) enhanced the bactericidal activity of macrophages and reduced organ damage during sepsis. Mechanistically, PPA directly binds to sirtuin 2 (SIRT2) and increases reactive oxygen species (ROS) production for eventual bacterial clearance. Importantly, PPA enhanced the bacterial clearance capacity of macrophages in sepsis patients and was inversely correlated with the severity of sepsis in patients. Our findings highlight the crucial contribution of commensal fungi to bacterial disease modulation and expand our understanding of the host-mycobiome interaction during sepsis development. © 2023, The Author(s), under exclusive licence to CSI and USTC.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Liu, RuofanSouthern Medical University, Guangzhou, China (author)
  • Yang, QinSouthern Medical University, Guangzhou, China (author)
  • Xie, LiSouthern Medical University, Guangzhou, China (author)
  • Wei, RongjuanSouthern Medical University, Guangzhou, China (author)
  • Li, JiaxinSouthern Medical University, Guangzhou, China (author)
  • Mei, FengyiSouthern Medical University, Guangzhou, China (author)
  • Chen, TaoSouthern Medical University, Guangzhou, China (author)
  • Zeng, ZhenhuaSouthern Medical University, Guangzhou, China (author)
  • He, YanSouthern Medical University, Guangzhou, China (author)
  • Zhou, HongweiSouthern Medical University, Guangzhou, China (author)
  • Peng, HongjuanSouthern Medical University, Guangzhou, China (author)
  • Nandakumar, Kutty Selva,1965-Högskolan i Halmstad,Akademin för företagande, innovation och hållbarhet(Swepub:hh)kutnam (author)
  • Chu, HuikuanTongji Medical College, Wuhan, China (author)
  • Jiang, YongSouthern Medical University, Guangzhou, China (author)
  • Gong, WeiSouthern Medical University, Guangzhou, China (author)
  • Chen, YeSouthern Medical University, Guangzhou, China (author)
  • Schnabl, BerndDepartment of Medicine, San Diego, United States (author)
  • Chen, PengSouthern Medical University, Guangzhou, China (author)
  • Southern Medical University, Guangzhou, ChinaAkademin för företagande, innovation och hållbarhet (creator_code:org_t)

Related titles

  • In:Cellular & Molecular ImmunologyLondon : Nature Publishing Group20:10, s. 1156-11701672-76812042-0226

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