Functional analysis of Bucella reveals transcriptional regulation of MarR

Abstract

Brucellosis is a zoonotic infectious disease caused by Brucella infection. MarR-family transcription factors are closely related to diverse physiological functions necessary for many pathogens adaptation to environmental changes. However, whether the MarR-family transcription factors are involved in virulence, mediated inflammatory responses and regulated virulence gene expression in the intracellular pathogen Brucella are still unknown. Therefore, we created a 2308ΔMarR6 mutant of B. abortus 2308 (S2308). Virulence and inflammatory cytokines assays were performed using a murine macrophage cell line (RAW 264.7). We also performed chromatin immunoprecipitation of MarR6 followed by next-generation sequencing (ChIP-seq). The results showed that 2308ΔMarR6 was significantly reduced survival capability in RAW 264.7. After the macrophages were infected with 2308ΔMarR6, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12), interferon-gamma (IFN-γ) and macrophage chemoattractant protein-1 (MCP-1) were decreased and were significantly lower than that for the S2308-infected group, indicating that the 2308ΔMarR6 mutant could reduce the secretion of inflammatory cytokines. Furthermore, we detected 122 intergenic ChIP-seq peaks of MarR6 binding distributed across the Brucella genome. Taken together, the research has recorded valuable data about MarR6. Our findings are of great significance in elucidating the function of MarR6.