Listeria monocytogenesMerR-Like Regulator NmlR_lm: Its Transcriptome and Role in Stress Response

Abstract

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 ΔnmlRlm strains 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 σ(H). Phenotypic characterization revealed that the ΔnmlRlm strain 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, nmlRlm deletion 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 NmlRlm is 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 σ(H).

Transcriptomic Analysis of the Adaptation of Listeria monocytogenes to Lagoon and Soil Matrices Associated with a Piggery Environment: Comparison of Expression Profiles

“…We identified as downregulated the genes encoding the cold shock proteins CspB and CspL and the heat shock protein GroES. The transcriptional regulator NmlR involved in oxidative stress and in tolerance to acid (Supa-amornkul et al, 2016 ) was found to be activated while the general stress protein encoded by lmo1601 was downregulated. L. monocytogenes is ubiquitous in the environment.…”

The MerR‐family regulator NmlR is involved in the defense against oxidative stress in Streptococcus pneumoniae

“…Additionally, AdhC was required for systemic virulence of S. pneumoniae in a mouse model by promoting the survival in the blood (Stroeher et al, 2007). Similarly, other MerR/NmlR homologs were characterized in Haemophilus influenzae , Bacillus subtilis , Listeria monocytogenes , Neisseria gonorrhoeae and Neisseria meningitidis and were shown to control the expression of conserved adhC genes, which conferred resistance under GSNO, H 2 O 2 and carbonyl stress and during infections (Chen et al, 2013; Counago et al, 2016; Kidd et al, 2005; Nguyen et al, 2009; Supa‐Amornkul et al, 2016).…”

Molecular Evolution of Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa Strains From Patients and Hospital Environment in a Prolonged Outbreak

“…As MerR acts as a repressor to block transcription initiation of the mer operon, a functionally deleterious SNP in the merR gene likely results in constitutive expression of the mer operon. We assume that this would increase the respective strains' ability to withstand environmental stressors, possibly related to other cytotoxic agents beyond mercury, as is known for a negative transcription regulator in the merR family for Neisseria gonorrhoeae and Haemophilus influenzae (Supa-Amornkul et al, 2016). In this light, this mutation can be seen as a gain-of-fitness determinant especially in the hospital environment with exposure to various disinfectants and cleaning agents.…”