Role of Carbon Monoxide-producing Escherichia Coli Nissle 1917 in Reducing the Severity of Inflammatory and Infectious Diseases in Mice

Pablo Reyes-Bustos – Pontificia Universidad Católica de Chile; Guillermo Hoppe-Elsholz – Pontificia Universidad Católica de Chile; Eduardo Tognarelli – Pontificia Universidad Católica de Chile; Sofía Campos-Gajardo – Pontificia Universidad Católica de Chile; Alejandro Piña-Iturbe – Pontificia Universidad Católica de Chile; Irenice Coronado-Arrázola – Pontificia Universidad Católica de Chile; Patricia Pereira-Sánchez – Pontificia Universidad Católica de Chile; Pedro Silva – Pontificia Universidad Católica de Chile; Francisco Quero – Pontificia Universidad Católica de Chile; Valentina Scaff – Pontificia Universidad Católica de Chile; Lucas Vásquez – Pontificia Universidad Católica de Chile; Alexis Kalergis – Pontificia Universidad Católica de Chile; Pablo González – Pontificia Universidad Católica de Chile; Susan Bueno – Pontificia Universidad Católica de Chile

Abstract Text: Chronic infections and inflammatory diseases are a significant global health challenge due to rising prevalence and the limited efficacy of existing treatments. The enzyme heme oxygenase-1 (HO-1) in mammals has been widely recognized for its immunomodulatory effects, particularly through its byproducts like carbon monoxide (CO), which play key roles in controlling inflammation. However, no approved therapies currently target HO-1 activation. Probiotic bacteria have emerged as a promising approach for enhancing host responses to infections and inflammatory diseases. Among them, Escherichia coli Nissle 1917 (EcN), a well-studied probiotic with immunomodulatory properties, encodes a bacterial HO-1 homolog, ChuS, which contributes to heme utilization and CO production.

In this study, we explored the role of ChuS in CO production and its impact on inflammation and infection. Using molecular genetics alongside in vitro and in vivo models, we demonstrated that ChuS activity enhances CO production in both settings and is essential for protection against DSS-induced colitis and herpes simplex virus type 1 (HSV-1) infection. Our results indicate that ChuS not only facilitates CO production but also reducing tissue damage and promoting host resilience during these conditions. These findings highlight ChuS as a key player in microbial CO production and suggest its therapeutic potential for modulating inflammatory responses. Using probiotics like EcN for CO delivery provides a solid basis for developing innovative therapeutic strategies targeting inflammatory and infectious diseases.

This work was supported by FONDEF IDeA ID20I10082, Fondecyt Regular 1231905 and the Millennium Institute on Immunology and Immunotherapy (ICM-ANID ICN2021_045), a FOCIS Center of Excellence.