Listeria monocytogenes MerR-Like Regulator NmlR<inf>lm</inf>: Its Transcriptome and Role in Stress Response

Abstract

© Copyright 2016, Mary Ann Liebert, Inc. 2016. NmlR, a negative transcription regulator in the MerR family, is involved in oxidative and nitrosative stress response in Neisseria gonorrhoeae and Haemophilus influenzae. In this study, the objective was to characterize the role and the regulon of NmlR in the foodborne Listeria monocytogenes. An L. monocytogenes nmlR null mutant strain was constructed. Transcriptomes of strain 10403S wild type (WT) and ΔnmlRlmstrains grown to the stationary phase were determined by mRNA sequencing. Differential expression analyses revealed 74 genes with altered expression levels (>9-fold difference), comprising 46 negatively and 28 positively regulated genes. Twenty-four NmlRlm-dependent genes overlap with the members of previously identified regulons of HrcA, a negative regulator of heat response in L. monocytogenes, and of alternative sigma factor σH. Phenotypic characterization revealed that the ΔnmlRlmstrain survived significantly less than the WT under acid stress (pH 2.5 for 1 h) and oxidative stress (3% hydrogen peroxide for 1 h). In addition, nmlRlmdeletion also resulted in a significant decrease (p < 0.0005) of cell length and enhanced intracellular growth in a differentiated macrophage-like U937 cell line during entry into stationary phase. These findings indicate that NmlRlmis not only involved in oxidative stress response but also contributes to other characteristics such as acid tolerance and intracellular growth, either through direct regulation or co-regulation with other regulators such as HrcA and σH.