Transcriptional profiling of the L. monocytogenes PrfA regulon identifies six novel putative PrfA-regulated genes

2020 ◽  
Vol 367 (22) ◽  
Author(s):  
L O Henderson ◽  
A Gaballa ◽  
R H Orsi ◽  
K J Boor ◽  
M Wiedmann ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Transcriptional Profiling ◽  
Fine Tuning ◽  
Upstream Open Reading Frame ◽  
Bacterial Gene ◽  
Transcript Levels ◽  
Reading Frame ◽  
Bacterial Gene Expression ◽  
Expression Of Genes ◽  
Constitutively Active

ABSTRACT The transcriptional activator Positive Regulatory Factor A (PrfA) regulates expression of genes essential for virulence in Listeria monocytogenes. To define the PrfA regulon, the 10403S wildtype (WT) strain, a constitutively active prfA* mutant, and an isogenic ∆prfA mutant were grown under PrfA-inducing conditions in a medium containing glucose-1-phosphate and pre-treated with 0.2% activated charcoal. RNA-seq-generated transcript levels were compared as follows: (i) prfA* and WT; (ii) WT and ∆prfA and (iii) prfA* and ∆prfA. Significantly higher transcript levels in the induced WT or constitutively active PrfA* were identified for 18 genes and 2 ncRNAs in at least one of the three comparisons. These genes included: (i) 10/12 of the genes previously identified as directly PrfA-regulated; (ii) 2 genes previously identified as PrfA-regulated, albeit likely indirectly; and (iii) 6 genes newly identified as PrfA-regulated, including one (LMRG_0 2046) with a σA-dependent promoter and PrfA box located within an upstream open reading frame. LMRG_0 2046, which encodes a putative cyanate permease, is reported to be downregulated by a σB-dependent anti-sense RNA. This newly identified overlap between the σB and PrfA regulons highlights the complexity of regulatory networks important for fine-tuning bacterial gene expression in response to the rapidly changing environmental conditions associated with infection.

scholarly journals RyhB, an Iron-Responsive Small RNA Molecule, Regulates Shigella dysenteriae Virulence

2007 ◽  
Vol 75 (7) ◽  
pp. 3470-3477 ◽  
Author(s):  
Erin R. Murphy ◽  
Shelley M. Payne
Keyword(s):  
Small Rna ◽  
Type Iii Secretion ◽  
Bacillary Dysentery ◽  
Shigella Dysenteriae ◽  
Virulence Determinants ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Expression Of Genes ◽  
Single Stranded Region ◽  
Complex Regulation

ABSTRACT Regulation of bacterial gene expression by small RNA (sRNA) molecules is an increasingly recognized phenomenon but one that is not yet fully understood. We show that the sRNA RyhB suppresses several virulence-associated phenotypes of Shigella dysenteriae, a causative agent of bacillary dysentery in humans. The virulence genes repressed by S. dysenteriae RyhB include those encoding the type III secretion apparatus, its secreted effectors, and specific chaperones. Suppression of Shigella virulence occurs via RyhB-dependent repression of the transcriptional activator VirB, leading to reduced expression of genes within the VirB regulon. Efficient repression of virB is mediated by a single-stranded region of RyhB that is distinct from the region required for repression of Shigella sodB. Regulation of virB by RyhB implicates iron as an environmental factor contributing to the complex regulation of Shigella virulence determinants.

scholarly journals miR-128 Is Implicated in Stress Responses by Targeting MAFG in Skeletal Muscle Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Rocco Caggiano ◽  
Fabio Cattaneo ◽  
Ornella Moltedo ◽  
Giovanni Esposito ◽  
Cinzia Perrino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Regulatory Networks ◽  
Transcriptional Regulator ◽  
Fine Tuning ◽  
Mrna Levels ◽  
Molecular Phenotype ◽  
Expression Of Genes ◽  
Direct Target ◽  
The Impact

MAFG (v-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) is a bZIP-type transcriptional regulator that belongs to the small MAF (sMAFs) protein family. By interacting with other bZIP transcription factors, sMAFs can form homo- and heterodimers governing either repressive or activating transcriptional functions. As heterodimeric partner of Nrf2, MAFG positively influences the ARE-dependent antioxidant/xenobiotic pathways, at least in condition of a correct MAFG:Nrf2 balance. MicroRNAs (miRs) participate to different regulatory networks being involved as fine-tuning regulators of gene expression. However, the connections between cellular surveillance to stresses mediated by MAFG:Nrf2 and miR regulations are not well understood. Here, we explored the impact of miR-128 in expression of genes related to stress response. Bioinformatic predictions coupled with functional analysis revealed the presence of miR-128 binding site in the 3′UTR of MAFG. Ectopic miR-128 expression correlated with reduced expression of endogenous MAFG-dependent genes and negatively affected ARE-mediated molecular phenotype based on Nrf2 activity. Indeed, miR-128 impairs redox-dependent pathways induced in response to oxidative stress. Moreover, in condition of hypoxia, MAFG induction correlated with reduced levels of miR-128. This lead to increased mRNA levels of HMOX-1 and x-CT for blunting stress. Overall, these findings identify MAFG as novel direct target of miR-128.

scholarly journals An Integrated Database of Small RNAs and Their Interplay With Transcriptional Gene Regulatory Networks in Corynebacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariana Teixeira Dornelles Parise ◽  
Doglas Parise ◽  
Flavia Figueira Aburjaile ◽  
Anne Cybelle Pinto Gomide ◽  
Rodrigo Bentes Kato ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Small Rnas ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Transcriptional Regulatory ◽  
Animal Pathogens ◽  
Gene Regulatory

Small RNAs (sRNAs) are one of the key players in the post-transcriptional regulation of bacterial gene expression. These molecules, together with transcription factors, form regulatory networks and greatly influence the bacterial regulatory landscape. Little is known concerning sRNAs and their influence on the regulatory machinery in the genus Corynebacterium, despite its medical, veterinary and biotechnological importance. Here, we expand corynebacterial regulatory knowledge by integrating sRNAs and their regulatory interactions into the transcriptional regulatory networks of six corynebacterial species, covering four human and animal pathogens, and integrate this data into the CoryneRegNet database. To this end, we predicted sRNAs to regulate 754 genes, including 206 transcription factors, in corynebacterial gene regulatory networks. Amongst them, the sRNA Cd-NCTC13129-sRNA-2 is predicted to directly regulate ydfH, which indirectly regulates 66 genes, including the global regulator glxR in C. diphtheriae. All of the sRNA-enriched regulatory networks of the genus Corynebacterium have been made publicly available in the newest release of CoryneRegNet(www.exbio.wzw.tum.de/coryneregnet/) to aid in providing valuable insights and to guide future experiments.

scholarly journals Diversity and Versatility in Small RNA-Mediated Regulation in Bacterial Pathogens

2021 ◽  
Vol 12 ◽  
Author(s):  
Brice Felden ◽  
Yoann Augagneur
Keyword(s):  
Gene Expression ◽  
High Throughput Screening ◽  
Regulatory Networks ◽  
Target Genes ◽  
Bacterial Pathogens ◽  
Regulation Of Gene Expression ◽  
Transcriptional Level ◽  
Large Set ◽  
Bacterial Gene ◽  
Bacterial Gene Expression

Bacterial gene expression is under the control of a large set of molecules acting at multiple levels. In addition to the transcription factors (TFs) already known to be involved in global regulation of gene expression, small regulatory RNAs (sRNAs) are emerging as major players in gene regulatory networks, where they allow environmental adaptation and fitness. Developments in high-throughput screening have enabled their detection in the entire bacterial kingdom. These sRNAs influence a plethora of biological processes, including but not limited to outer membrane synthesis, metabolism, TF regulation, transcription termination, virulence, and antibiotic resistance and persistence. Almost always noncoding, they regulate target genes at the post-transcriptional level, usually through base-pair interactions with mRNAs, alone or with the help of dedicated chaperones. There is growing evidence that sRNA-mediated mechanisms of actions are far more diverse than initially thought, and that they go beyond the so-called cis- and trans-encoded classifications. These molecules can be derived and processed from 5' untranslated regions (UTRs), coding or non-coding sequences, and even from 3' UTRs. They usually act within the bacterial cytoplasm, but recent studies showed sRNAs in extracellular vesicles, where they influence host cell interactions. In this review, we highlight the various functions of sRNAs in bacterial pathogens, and focus on the increasing examples of widely diverse regulatory mechanisms that might compel us to reconsider what constitute the sRNA.

scholarly journals Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg2+

2019 ◽  
Vol 47 (12) ◽  
pp. 6478-6487 ◽  
Author(s):  
Kaley McCluskey ◽  
Julien Boudreault ◽  
Patrick St-Pierre ◽  
Cibran Perez-Gonzalez ◽  
Adrien Chauvier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Molecule ◽  
Fine Tuning ◽  
Regulatory Function ◽  
Divalent Metal Ions ◽  
Ligand Complex ◽  
Physiological Concentration ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Amino Acid Sensing

Abstract Riboswitches are cis-acting regulatory RNA biosensors that rival the efficiency of those found in proteins. At the heart of their regulatory function is the formation of a highly specific aptamer–ligand complex. Understanding how these RNAs recognize the ligand to regulate gene expression at physiological concentrations of Mg2+ ions and ligand is critical given their broad impact on bacterial gene expression and their potential as antibiotic targets. In this work, we used single-molecule FRET and biochemical techniques to demonstrate that Mg2+ ions act as fine-tuning elements of the amino acid-sensing lysC aptamer's ligand-free structure in the mesophile Bacillus subtilis. Mg2+ interactions with the aptamer produce encounter complexes with strikingly different sensitivities to the ligand in different, yet equally accessible, physiological ionic conditions. Our results demonstrate that the aptamer adapts its structure and folding landscape on a Mg2+-tunable scale to efficiently respond to changes in intracellular lysine of more than two orders of magnitude. The remarkable tunability of the lysC aptamer by sub-millimolar variations in the physiological concentration of Mg2+ ions suggests that some single-aptamer riboswitches have exploited the coupling of cellular levels of ligand and divalent metal ions to tightly control gene expression.

scholarly journals The quorum sensing system NprR-NprRB contributes to spreading and fitness in colony biofilms of Bacillus thuringiensis

2021 ◽  
Author(s):  
Abel Verdugo-Fuentes ◽  
Mayra de la Torre ◽  
Jorge Rocha
Keyword(s):  
Bacillus Thuringiensis ◽  
Quorum Sensing ◽  
Receptor Protein ◽  
Protein Signaling ◽  
Experimental Conditions ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Extracellular Signaling ◽  
Expression Of Genes ◽  
Exogenous Addition

AbstractQuorum sensing (QS) are intercellular communication mechanisms to coordinate bacterial gene expression in response to signaling molecules. In Bacillus thuringiensis the QS system NprR-NprRB (receptor protein-signaling peptide) regulates the expression of genes related to nutrient scavenging during necrotrophism and also modulates sporulation onset. However, the relevance of QS in free-living stages of B. thuringiensis is less known. In this work, we depict the contribution of this QS system to spreading in colony biofilms. Through a spreading assay in spotted colonies of B. thuringiensis Bt8741 Wt and derived mutants, we find that the spreading phenotype depends on the NprR regulator and on the extracellular signaling NprRB peptide. We also show that this phenotype is associated to an increased fitness of the bacterium in these experimental conditions. Exogenous addition of a lipopeptide surfactant was sufficient to recover spreading in the ΔnprR-nprRB mutant, indicating that the phenotype could be mediated by the lipopeptide kurstakin. Finally, we suggest that the spreading is relevant in nature, since it occurs in the sole presence of soil nutrients, and it is conserved in several species of Bacillus commonly found in soil. This novel function of NprR-NprRB highlights the relevance of this QS system on the evolution and on the free-lifestyle ecology of B. thuringiensis.

scholarly journals Microarray Analysis of Bacterial Gene Expression: Towards the Regulome

2002 ◽  
Vol 3 (4) ◽  
pp. 352-354 ◽  
Author(s):  
Sharon L. Kendall ◽  
Farahnaz Movahedzadeh ◽  
Andreas Wietzorrek ◽  
Neil G. Stoker
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Type Strain ◽  
Regulatory Networks ◽  
Wild Type Strain ◽  
Microarray Technology ◽  
Wild Type ◽  
Bacterial Gene ◽  
Bacterial Gene Expression

Microarray technology allows co-regulated genes to be identified. In order to identify genes that are controlled by specific regulators, gene expression can be compared in mutant and wild-type bacteria. However, there are a number of pitfalls with this approach; in particular, the regulator may not be active under the conditions in which the wild-type strain is cultured. Once co-regulated genes have been identified, proteinbinding motifs can be identified. By combining these data with a map of promoters, or operons (the operome), the regulatory networks in the cell (the regulome) can start to be built up.

scholarly journals Cell-Specific Transcriptional Profiling Reveals Candidate Mechanisms Regulating Development and Function of Uterine Epithelia in Mice

2013 ◽  
Vol 89 (4) ◽  
Author(s):  
Justyna Filant ◽  
Thomas E. Spencer
Keyword(s):  
Regulatory Networks ◽  
Transcriptional Profiling ◽  
Uterine Receptivity ◽  
Bioactive Substances ◽  
Retinoid Signaling ◽  
Expression Of Genes ◽  
Epithelial Development ◽  
Uterine Gland ◽  
Blastocyst Implantation ◽  
And Function

Abstract All mammalian uteri have luminal (LE) and glandular epithelia (GE) in their endometrium. The LE mediates uterine receptivity and blastocyst attachment for implantation, and the GE synthesize and secrete or transport bioactive substances involved in blastocyst implantation, uterine receptivity, and stromal cell decidualization. However, the mechanisms governing uterine epithelial development after birth and their function in the adult are not fully understood. Here, comprehensive microarray analysis was conducted on LE and GE isolated by laser capture microdissection from uteri on Postnatal Day 10 (PD 10) and day of pseudopregnancy (DOPP) 2.5 and 3.5. This data was integrated with analysis of uteri from gland-containing control and aglandular progesterone-induced uterine gland knockout mice from PD 10 and DOPP 3.5. Many genes were expressed in both epithelia, but there was greater expression of genes in the LE than in the GE. In the neonate, GE-expressed genes were enriched for morphogenesis, development, migration, and retinoic acid signaling. In the adult, LE-expressed genes were enriched for metabolic processes and steroid biosynthesis, whereas retinoid signaling, tight junction, extracellular matrix, and regulation of kinase activity were enriched in the GE. The transcriptome differences in the epithelia support the idea that each cell type has a distinct and complementary function in the uterus. The candidate genes and regulatory networks identified here provide a framework to discover new mechanisms regulating development of epithelia in the postnatal uterus and their functions in early pregnancy.

scholarly journals Prophage BPs Alters Mycobacterial Gene Expression and Antibiotic Resistance

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 67
Author(s):  
Sally Molloy ◽  
Jaycee Cushman ◽  
Emma Freeman ◽  
Keith Hutchison
Keyword(s):  
Gene Expression ◽  
Antibiotic Resistance ◽  
Virulence Gene ◽  
Bacterial Gene ◽  
Viral Genomes ◽  
Bacterial Gene Expression ◽  
Expression Of Genes ◽  
Genus Mycobacterium ◽  
Ctx Prophage ◽  
The Impact

Diseases caused by mycobacteria such as Mycobacterium tuberculosis are the leading cause of death worldwide. With the emergence of strains that are resistant to first-line anti-tuberculosis drugs and naturally drug-resistant pathogens such as M. abscessus, there is a need to increase our understanding of mycobacterial fitness and virulence and identify new targets for drugs. The majority of the pathogenic species of the bacterial genus Mycobacterium, including M. tuberculosis, carry integrated viral genomes (prophages) that are hypothesized to contribute to virulence. Though we know many of the ways in which phage genes directly contribute to pathogenesis, e.g., the CTX prophage encodes the toxin in Vibrio cholera, we know little about the impact of phages that encode no obvious toxin or virulence gene. Using an RNAseq approach, our lab recently showed for the first time that the presence of a prophage alters the expression of 7.4% of genes in the pathogenic mycobacterial species, M. chelonae. The presence of prophage BPs increased the expression of genes in the whiB7 regulon, including whiB7, eis2, and tap, and decreased the expression of a padR-family transcription factor. BP lysogens were more resistant to aminoglycosides (kanamycin and amikacin) and tetracycline than wild-type strains of M. chelonae. In order to determine how the BP prophage drives changes in bacterial gene expression and phenotype, we will test the effects of individual BP genes expressed during lysogeny, such as the immunity repressor, on bacterial gene expression and antibiotic resistance phenotypes.

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