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.

中文翻译：

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单核细胞增生李斯特菌SpxA1是激活有氧代谢的过氧化氢酶和血红素生物合成酶编码基因所需的全球调节剂。

细胞氧化剂和还原剂的不平衡会导致氧化还原应激，必须迅速检测氧化还原应激才能恢复体内平衡。在细菌中，Firmicutes编码保守的Spx家族转录调节因子，该调节因子响应氧化还原应激而调节转录。SpxA1是细胞内病原体单核细胞增生李斯特氏菌中的Spx家族直系同源物，对有氧生长和发病机理至关重要。在这里，我们通过鉴定肉汤和巨噬细胞感染过程中SpxA1调控的基因来研究SpxA1在生长和毒力中的作用。我们发现单核细胞增生李斯特氏菌需要SpxA1激活的编码血红素生物合成酶和过氧化氢酶（kat）的基因在有氧培养基中有氧生长。以前在枯草芽孢杆菌中定义的Spx识别基序在SpxA1激活的基因的启动子中被发现，并被证明对于两个基因的正确激活是必要的，这表明SpxA1的这种调控可能是直接的。在一起，这些发现阐明了spxA1必需性的体外机制，并证明SpxA1是清除酶的基础表达以抵抗在氧气存在下产生的氧化还原应激所必需的。