Bacterial Quorum Sensing Peptides and their muscle talk

August 26, 2022

Quorum sensing molecules (QSM) are characteristic bacterial products, constitutively produced by living bacteria and exhibiting an increased and/or altered production in “stress” conditions. Mainly three groups can be distinguished: the N-acyl-homoserine-lactones (AHL, mainly produced by Gram-negative bacteria), the quorum sensing peptides (QSP, mainly produced by Gram-positive bacteria) and the furanosyl borates (AI-2 [autoinducer-2], produced by Gram-positive as well as Gram-negative bacteria). Quorum sensing peptides have long been considered as intra-bacterial communication molecules only [1, 2]. However, nowadays, it is generally accepted that this communication is not limited to the bacteria themselves, but also play a role in for example colorectal cancer and the central nervous system. We recently identified iAM373, a QSP produced by E. faecalis, to be an inducer of sarcopenia [3, 4]. iAM373 was shown to 1) decrease metabolic activity in vitro, 2) induce a sarcopenic phenotype in C. elegans in vivo, 3) be present in murine and human plasma and 4) correlate with muscle mass and gait speed in older people [4]. These findings offer the first demonstration that quorum sensing molecules are involved in muscle wasting diseases such as sarcopenia, opening new diagnostic and therapeutic dimensions.

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[2] E. Wynendaele, A. Bronselaer, J. Nielandt, M. D'Hondt, S. Stalmans, N. Bracke, F. Verbeke, C. Van De Wiele, G. De Tre, B. De Spiegeleer, Quorumpeps database: chemical space, microbial origin and functionality of quorum sensing peptides, Nucleic Acids Research 41(D1) (2013) D655-D659.
[3] A. De Spiegeleer, D. Elewaut, N. Van den Noortgate, Y. Janssens, N. Debunne, S. Van Langenhove, S. Govindarajan, B. De Spiegeleer, E. Wynendaele, Quorum sensing molecules as a novel microbial factor impacting muscle cells, Biochimica Et Biophysica Acta-Molecular Basis of Disease 1866(3) (2020).
[4] A. De Spiegeleer, E. Wynendaele, N. Debunne, B. Braeckman, M. De Mey, A. Descamps, J. Coudenys, L. Crombez, F. Verbeke, D. Elewaut, Bacterial Quorum Sensing Peptides and Sarcopenia: a role for iAM373, Clinical and Translational Medicine (2022) Revised manuscript under review.