scholarly journals Attenuator LRR – a regulatory tool for modulating gene expression in Gram‐positive bacteria

2021 ◽  
Author(s):  
Xia Cai ◽  
Qian Wang ◽  
Yu Fang ◽  
Die Yao ◽  
Yunda Zhan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gram Positive ◽  
Gram Positive Bacteria

scholarly journals Resilience in the Face of Uncertainty: Sigma Factor B Fine-Tunes Gene Expression To Support Homeostasis in Gram-Positive Bacteria

2016 ◽  
Vol 82 (15) ◽  
pp. 4456-4469 ◽  
Author(s):  
Claudia Guldimann ◽  
Kathryn J. Boor ◽  
Martin Wiedmann ◽  
Veronica Guariglia-Oropeza
Keyword(s):  
Gene Expression ◽  
Sigma Factor ◽  
Environmental Changes ◽  
Regulation Of Gene Expression ◽  
Bacterial Survival ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Changing Environments ◽  
The Face

ABSTRACTGram-positive bacteria are ubiquitous and diverse microorganisms that can survive and sometimes even thrive in continuously changing environments. The key to such resilience is the ability of members of a population to respond and adjust to dynamic conditions in the environment. In bacteria, such responses and adjustments are mediated, at least in part, through appropriate changes in the bacterial transcriptome in response to the conditions encountered. Resilience is important for bacterial survival in diverse, complex, and rapidly changing environments and requires coordinated networks that integrate individual, mechanistic responses to environmental cues to enable overall metabolic homeostasis. In many Gram-positive bacteria, a key transcriptional regulator of the response to changing environmental conditions is the alternative sigma factor σB. σBhas been characterized in a subset of Gram-positive bacteria, including the generaBacillus,Listeria, andStaphylococcus. Recent insight from next-generation-sequencing results indicates that σB-dependent regulation of gene expression contributes to resilience, i.e., the coordination of complex networks responsive to environmental changes. This review explores contributions of σBto resilience inBacillus,Listeria, andStaphylococcusand illustrates recently described regulatory functions of σB.

scholarly journals Small-Molecule Antibiotics Inhibiting tRNA-Regulated Gene Expression Is a Viable Strategy for Targeting Gram-Positive Bacteria

2020 ◽  
Vol 65 (1) ◽  
pp. e01247-20 ◽  
Author(s):  
Ville Y. P. Väre ◽  
Ryan F. Schneider ◽  
Haein Kim ◽  
Erica Lasek-Nesselquist ◽  
Kathleen A. McDonough ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Molecule ◽  
Bacterial Infections ◽  
Gram Positive ◽  
Content Type ◽  
T Box ◽  
Gram Positive Bacteria ◽  
Bactericidal Effects ◽  
Low Levels ◽  
Regulated Gene Expression

ABSTRACTBacterial infections and the rise of antibiotic resistance, especially multidrug resistance, have generated a clear need for discovery of novel therapeutics. We demonstrated that a small-molecule drug, PKZ18, targets the T-box mechanism and inhibits bacterial growth. The T-box is a structurally conserved riboswitch-like gene regulator in the 5′ untranslated region (UTR) of numerous essential genes of Gram-positive bacteria. T-boxes are stabilized by cognate, unacylated tRNA ligands, allowing the formation of an antiterminator hairpin in the mRNA that enables transcription of the gene. In the absence of an unacylated cognate tRNA, transcription is halted due to the formation of a thermodynamically more stable terminator hairpin. PKZ18 targets the site of the codon-anticodon interaction of the conserved stem I and reduces T-box-controlled gene expression. Here, we show that novel analogs of PKZ18 have improved MICs, bactericidal effects against methicillin-resistant Staphylococcus aureus (MRSA), and increased efficacy in nutrient-limiting conditions. The analogs have reduced cytotoxicity against eukaryotic cells compared to PKZ18. The PKZ18 analogs acted synergistically with aminoglycosides to significantly enhance the efficacy of the analogs and aminoglycosides, further increasing their therapeutic windows. RNA sequencing showed that the analog PKZ18-22 affects expression of 8 of 12 T-box controlled genes in a statistically significant manner, but not other 5′-UTR regulated genes in MRSA. Very low levels of resistance further support the existence of multiple T-box targets for PKZ18 analogs in the cell. Together, the multiple targets, low resistance, and synergy make PKZ18 analogs promising drugs for development and future clinical applications.

scholarly journals RNA polymerases from Low G+C Gram Positive Bacteria

2021 ◽  
Author(s):  
Michael Miller ◽  
Aaron Oakley ◽  
Peter Lewis
Keyword(s):  
Gene Expression ◽  
Structural Information ◽  
Gram Positive ◽  
Control Of Gene Expression ◽  
Gram Negative ◽  
Auxiliary Subunits ◽  
Gram Positive Bacteria ◽  
High Resolution Structure ◽  
Resolution Structure

The low G+C Gram positive bacteria represent some of the most medically and industrially important microorganisms. They are relied on for the production of food and dietary supplements, enzymes and antibiotics, as well as being responsible for the majority of nosocomial infections and serving as a reservoir for antibiotic resistance. Control of gene expression in this group is more highly studied than in any bacteria other than the Gram negative model Escherichia coli, yet until recently no structural information on RNA polymerase (RNAP) from this group was available. This review will summarise recent reports on the high resolution structure of RNAP from the model low G+C representative Bacillus subtilis, including the role of auxiliary subunits δ and ε, and outline approaches for the development of antimicrobials to target RNAP from this group.

scholarly journals A specific gene expression program triggered by Gram-positive bacteria in the cytosol

2004 ◽  
Vol 101 (31) ◽  
pp. 11386-11391 ◽  
Author(s):  
R. L. McCaffrey ◽  
P. Fawcett ◽  
M. O'Riordan ◽  
K.-D. Lee ◽  
E. A. Havell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Program ◽  
Specific Gene ◽  
Gram Positive ◽  
Specific Gene Expression ◽  
Gram Positive Bacteria ◽  
Expression Program

scholarly journals Development of a Thermally Regulated Broad-Spectrum Promoter System for Use in Pathogenic Gram-Positive Species

2003 ◽  
Vol 69 (6) ◽  
pp. 3385-3392 ◽  
Author(s):  
David A. Schofield ◽  
Caroline Westwater ◽  
Brian D. Hoel ◽  
Phillip A. Werner ◽  
James S. Norris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Temperature Sensitive ◽  
Broad Host Range ◽  
Gram Positive ◽  
Bacteriophage P1 ◽  
Synthetic Promoters ◽  
Gram Positive Bacteria ◽  
Basal Expression ◽  
Broad Host Range Plasmid ◽  
Promoter System

ABSTRACT Selectively regulating gene expression is an essential molecular tool that is lacking for many pathogenic gram-positive bacteria. In this report, we describe the evaluation of a series of promoters regulated by the bacteriophage P1 temperature-sensitive C1 repressor in Enterococcus faecium, Enterococcus faecalis, and Staphylococcus aureus. Using the lacZ gene to monitor gene expression, we examined the strength, basal expression, and induced expression of synthetic promoters carrying C1 operator sites. The promoters exhibited extremely low basal expression and, under inducing conditions, gave high levels of expression (100- to 1,000-fold induction). We demonstrate that the promoter system could be modulated by temperature and showed rapid induction and that the mechanism of regulation occurred at the level of transcription. Controlled expression with the same constructs was also demonstrated in the gram-negative bacterium Escherichia coli. However, low basal expression and the ability to achieve derepression were dependent on both the number of mismatches in the C1 operator sites and the promoter driving c1 expression. Since the promoters were designed to contain conserved promoter elements from gram-positive species and were constructed in a broad-host-range plasmid, this system will provide a new opportunity for controlled gene expression in a variety of gram-positive bacteria.

scholarly journals Identification of New Chromosomal Loci Involved in com Genes Expression and Natural Transformation in the Actinobacterial Model Organism Micrococcus luteus

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1307
Author(s):  
Enzo Joaquin Torasso Kasem ◽  
Angel Angelov ◽  
Elisa Werner ◽  
Antoni Lichev ◽  
Sonja Vanderhaeghen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natural Transformation ◽  
Micrococcus Luteus ◽  
Model Organism ◽  
Competence Development ◽  
Chemical Mutagenesis ◽  
Reporter Strain ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Genes Expression

Historically, Micrococcus luteus was one of the first organisms used to study natural transformation, one of the main routes of horizontal gene transfer among prokaryotes. However, little is known about the molecular basis of competence development in M. luteus or any other representative of the phylum of high-GC Gram-positive bacteria (Actinobacteria), while this means of genetic exchange has been studied in great detail in Gram-negative and low-GC Gram-positive bacteria (Firmicutes). In order to identify new genetic elements involved in regulation of the comEA-comEC competence operon in M. luteus, we conducted random chemical mutagenesis of a reporter strain expressing lacZ under the control of the comEA-comEC promoter, followed by the screening of dysregulated mutants. Mutants with (i) upregulated com promoter under competence-repressing conditions and (ii) mutants with a repressed com promoter under competence-inducing conditions were isolated. After genotype and phenotype screening, the genomes of several mutant strains were sequenced. A selection of putative com-influencing mutations was reinserted into the genome of the M. luteus reporter strain as markerless single-nucleotide mutations to confirm their effect on com gene expression. This strategy revealed mutations affecting com gene expression at genetic loci different from previously known genes involved in natural transformation. Several of these mutations decreased transformation frequencies by several orders of magnitude, thus indicating significant roles in competence development or DNA acquisition in M. luteus. Among the identified loci, there was a new locus containing genes with similarity to genes of the tad clusters of M. luteus and other bacteria.

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