The quorum-sensing peptidic inhibitor rescues host immune system eradication: A novel infectivity mechanism - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2023

The quorum-sensing peptidic inhibitor rescues host immune system eradication: A novel infectivity mechanism

Abstract

Subverting the host immune system is a major task for any given pathogen to assure its survival and proliferation. For the opportunistic human pathogen Bacillus cereus (Bc), immune evasion enables the establishment of potent infections. In various species of the Bc group, the pleiotropic regulator PlcR and its cognate cell–cell signaling peptide PapR 7 regulate virulence gene expression in response to fluctuations in population density, i.e., a quorum-sensing (QS) system. However, how QS exerts its effects during infections and whether PlcR confers the immune evading ability remain unclear. Herein, we report how interception of the QS communication in Bc obliterates the ability to affect the host immune system. Here, we designed a peptide-based QS inhibitor that suppresses PlcR-dependent virulence factor expression and attenuates Bc infectivity in mouse models. We demonstrate that the QS peptidic inhibitor blocks host immune system–mediated eradication by reducing the expression of PlcR-regulated major toxins similarly to the profile that was observed for isogenic strains. Our findings provide evidence that Bc infectivity is regulated by QS circuit-mediated destruction of host immunity, thus reveal a interesting strategy to limit Bc virulence and enhance host defense. This peptidic quorum-quenching agent constitutes a readily accessible chemical tool for studying how other pathogen QS systems modulate host immunity and forms a basis for development of anti-infective therapeutics.

Dates and versions

hal-04276455 , version 1 (09-11-2023)

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Cite

Avishag Yehuda, Einav Malach, Shahar Vanunu Ofri, Leyla Slamti, Shanny Hsuan Kuo, et al.. The quorum-sensing peptidic inhibitor rescues host immune system eradication: A novel infectivity mechanism. Proceedings of the National Academy of Sciences of the United States of America, 2023, 120 (35), pp.e2301045120. ⟨10.1073/pnas.2301045120⟩. ⟨hal-04276455⟩
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