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Listeria monocytogenes SpxA1 is a global regulator required to activate genes encoding catalase and heme biosynthesis enzymes for aerobic growth.

Cesinger MR, Thomason MK, Edrozo MB, Halsey CR, Reniere ML. April, 2020.

An imbalance of cellular oxidants and reductants causes redox stress, which must be rapidly detected to restore homeostasis. In bacteria, the Firmicutes encode conserved Spx-family transcriptional regulators that modulate transcription in response to redox stress. SpxA1 is an Spx-family orthologue in the intracellular pathogen Listeria monocytogenes that is essential for aerobic growth and pathogenesis. Here, we investigated the role of SpxA1 in growth and virulence by identifying genes regulated by SpxA1 in broth and during macrophage infection. We found SpxA1-activated genes encoding heme biosynthesis enzymes and catalase (kat) were required for L. monocytogenes aerobic growth in rich medium. An Spx-recognition motif previously defined in Bacillus subtilis was identified in the promoters of SpxA1-activated genes and proved necessary for the proper activation of two genes, indicating this regulation by SpxA1 is likely direct. Together, these findings elucidated the mechanism of spxA1 essentiality in vitro and demonstrated that SpxA1 is required for basal expression of scavenging enzymes to combat redox stress generated in the presence of oxygen.

 

Molecular Microbiology. 2020 Apr 7;517(7533):170-3. doi: 10.1111/mmi.14508.

Publications  

A genome-wide screen in macrophages identifies PTEN as required for myeloid restriction of Listeria monocytogenes infection.

Glover RC, Schwardt NH, Leano SE, Sanchez ME, Thomason MK, Olive AJ, Reniere ML. 2023 PLoS Pathog. 19(5).

The Transcriptional Regulator SpxA1 Influences the Morphology and Virulence of Listeria monocytogenes.

Cesinger MR, Daramola OI, Kwiatowski LM, Reniere ML. 2022 Infect Immun. 90(10).

The redox-responsive transcriptional regulator Rex represses fermentative metabolism and is required for Listeria monocytogenes pathogenesis.

Halsey CR, Glover RC, Thomason MK, Reniere ML. 2021 PLoS Pathog. 17(8).

Investigating the roles of Listeria monocytogenes peroxidases in growth and virulence.

Cesinger MR*, Schwardt NH*, Halsey CR, Thomason MK, Reniere ML. 2021 Microbiol Spectr. 9(1).

YjbH requires its thioredoxin active motif for the nitrosative stress response, cell-to-cell spread, and protein-protein interactions in Listeria monocytogenes.

Ruhland BR, Reniere ML. 2020 J Bacteriol. 202(12).

Listeria monocytogenes SpxA1 is a global regulator required to activate genes encoding catalase and heme biosynthesis enzymes for aerobic growth. 

Cesinger MR, Thomason MK, Edrozo MB, Halsey CR, Reniere ML. 2020 Mol Microbiol. 114(2):230-243.

Sense and sensor ability: redox-responsive regulators in Listeria monocytogenes.

Ruhland BR, Reniere ML. 2018 Curr Opin Microbiol. 47:20-25.

Reduce, Induce, Thrive: Bacterial redox sensing during pathogenesis.

Reniere ML. 2018 J Bacteriol. 200(17).

A redox-responsive transcription factor is critical for pathogenesis and aerobic growth of Listeria monocytogenes.

Whiteley AW, Ruhland BR, Edrozo MB, Reniere ML. 2017 Infect Immun. 85(5).

An in vivo selection identifies Listeria monocytogenes genes required to sense the intracellular environment and activate virulence gene expression.

Reniere ML, Whiteley AT, Portnoy DA. 2016 PLoS Pathog, 12(7):e1005741.

Glutathione activates virulence gene expression of an intracellular pathogen.

Reniere ML, Whiteley AT, Hamilton KL, John SM, Lauer P, Brennan RG, Portnoy DA. 2015 Nature, 517(7533):170-3.

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