Meireles, D. | bioRxiv Science

bioRxiv2026

Structural mechanism of metal-induced DNA release by an ArsR/SmtB transcriptional regulator

Metal-responsive transcriptional regulators must couple metal coordination to DNA release at the DNA-binding interface. However, the pathway connecting these states remains poorly understood. Here, we define this mechanism for the ArsR/SmtB-family repressor CadC from Listeria monocytogenes by combining crystal structures of apo, DNA-bound, and cadmium-bound states with biochemical and in vivo analyses. The DNA-bound structure reveals how CadC dimers bind sequence-specifically to operator DNA, via coordinated major-groove, wing and backbone interactions, with high-affinity binding depending on operator architecture. Cadmium is coordinated at the 3N sensor by an unusual Cys3-Met ligand set and stabilizes a DNA-incompatible conformation through remodeling of DNA-contacting elements and steric incompatibility between the ordered N-terminus and DNA. Mutational analyses show how these structural transitions link to metal-dependent transcriptional control in Listeria cells. We show that CadC binds zinc and supports zinc-responsive transcription in bacterial cells, and that host zinc availability modifies CadC-dependent infection phenotypes. Together, results reveal how metal coordination is converted into DNA release through coupled allosteric remodeling and steric exclusion, establishing a mechanism for signal-dependent transcriptional switching in ArsR/SmtB metalloregulators.

microbiology↗

bioRxiv2021

Stabilin-1 plays a protective role against Listeria monocytogenes infection through the regulation of cytokine and chemokine production and immune cell recruitment

Scavenger receptors are part of a complex surveillance system expressed by host cells to efficiently orchestrate innate immune response against bacterial infections. Stabilin-1 (STAB-1) is a scavenger receptor involved in cell trafficking, inflammation and cancer, however its role in infection remains to be elucidated. Listeria monocytogenes (Lm) is a major intracellular human food-borne pathogen causing severe infections in susceptible hosts. Using a mouse model of infection, we demonstrate here that STAB-1 controls Lm-induced cytokine and chemokine production and immune cell accumulation in Lm-infected organs. We show that STAB-1 also regulates the recruitment of myeloid cells in response to Lm infection and contributes to clear circulating bacteria. In addition, whereas STAB-1 appears to promote bacterial uptake by macrophages, infection by pathogenic Listeria induces the down regulation of STAB-1 expression and its delocalization from the host cell membrane. We propose STAB-1 as a new SR involved in the control of Lm infection through the regulation of host defense mechanisms, a process that would be targeted by bacterial virulence factors to promote infection.

microbiology↗