Inactivation of lmo0946 (sif) induces the SOS response and MGEs mobilization and silences the general stress response and virulence program in Listeria monocytogenes

Magdalena Ładziak; Emilia Prochwicz; Karina Gut; Patrycja Gomza; Karolina Jaworska; Katarzyna Ścibek; Marta Młyńska-Witek; Katarzyna Kadej-Zajączkowska; Eva M S Lillebaek; Birgitte H Kallipolitis; Agata Krawczyk-Balska

doi:10.3389/fmicb.2023.1324062

Inactivation of lmo0946 (sif) induces the SOS response and MGEs mobilization and silences the general stress response and virulence program in Listeria monocytogenes

Front Microbiol. 2024 Jan 4:14:1324062. doi: 10.3389/fmicb.2023.1324062. eCollection 2023.

Affiliations

¹ Department of Molecular Microbiology, Biological and Chemical Research Centre, Faculty of Biology, University of Warsaw, Warsaw, Poland.
² Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.

Abstract

Bacteria have evolved numerous regulatory pathways to survive in changing environments. The SOS response is an inducible DNA damage repair system that plays an indispensable role in bacterial adaptation and pathogenesis. Here we report a discovery of the previously uncharacterized protein Lmo0946 as an SOS response interfering factor (Sif) in the human pathogen Listeria monocytogenes. Functional genetic studies demonstrated that sif is indispensable for normal growth of L. monocytogenes in stress-free as well as multi-stress conditions, and sif contributes to susceptibility to β-lactam antibiotics, biofilm formation and virulence. Absence of Sif promoted the SOS response and elevated expression of mobilome genes accompanied by mobilization of the A118 prophage and ICELm-1 mobile genetic elements (MGEs). These changes were found to be associated with decreased expression of general stress response genes from the σB regulon as well as virulence genes, including the PrfA regulon. Together, this study uncovers an unexpected role of a previously uncharacterized factor, Sif, as an inhibitor of the SOS response in L. monocytogenes.

Keywords: Listeria monocytogenes; MGEs mobilization; SOS response; stress response; virulence.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by the National Science Centre (Poland) through a grant to AK-B (grant no. 2016/21/B/NZ6/00963) and partially supported by EMBO Short-term Fellowship (no. ASTF 137) to AK-B. Publication was co-financed by “Excellence Initiative—Research University (2020–2026)” Program at the University of Warsaw.