A short-lived peptide signal regulates cell-to-cell communication in Listeria monocytogenes

Benjamin S. Bejder, Fabrizio Monda, Bengt H. Gless, Martin S. Bojer, Hanne Ingmer, Christian A. Olsen*

*Corresponding author af dette arbejde

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Abstract

Quorum sensing (QS) is a mechanism that regulates group behavior in bacteria, and in Gram-positive bacteria, the communication molecules are often cyclic peptides, called autoinducing peptides (AIPs). We recently showed that pentameric thiolactone-containing AIPs from Listeria monocytogenes, and from other species, spontaneously undergo rapid rearrangement to homodetic cyclopeptides, which hampers our ability to study the activity of these short-lived compounds. Here, we developed chemically modified analogues that closely mimic the native AIPs while remaining structurally intact, by introducing N-methylation or thioester-to-thioether substitutions. The stabilized AIP analogues exhibit strong QS agonism in L. monocytogenes and allow structure–activity relationships to be studied. Our data provide evidence to suggest that the most potent AIP is in fact the very short-lived thiolactone-containing pentamer. Further, we find that the QS system in L. monocytogenes is more promiscuous with respect to the structural diversity allowed for agonistic AIPs than reported for the more extensively studied QS systems in Staphylococcus aureus and Staphylococcus epidermidis. The developed compounds will be important for uncovering the biology of L. monocytogenes, and the design principles should be broadly applicable to the study of AIPs in other species. (Figure presented.)

OriginalsprogEngelsk
Artikelnummer942
TidsskriftCommunications Biology
Vol/bind7
Antal sider11
ISSN2399-3642
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
We gratefully acknowledge the Independent Research Fund Denmark\u2212Natural Sciences (Grant No. 0135-00427B; C.A.O.) and the LEO Foundation Open Competition Grant program (LF-OC-20-000517; M.S.B. and H.I., LF-OC-19-000039; C.A.O., and LF-OC-21-000901; C.A.O.) for financial support. We thank Prof. Christian Riedel (University of Ulm) for generously providing the bacterial strains used in the study.

Publisher Copyright:
© The Author(s) 2024.

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