Regulation of Metabolic Pathways by MarR Family Transcription Factors

Grove, Anne

doi:10.1016/j.csbj.2017.06.001

Cited by 67 publications

(68 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MarR transcription factor was first identified in Escherichia coli K-12 and shown to regulate resistance to diverse antibiotics, organic solvents, and oxidative stress agents (36,37). More than 54,000 genes that encode MarR proteins in bacteria and archaea have since been annotated according to Ensembl Bacteria, with an average of ϳ7 paralogs per genome (38). MarR family proteins, which have been suggested to have originated before the divergence of bacteria and archaea (39), belong to the very common winged helix-turn-helix (wHTH) subset of HTH proteins.…”

Section: Multiple Antibiotic Resistance Regulators (Marr)mentioning

confidence: 99%

“…All Burkholderia species encode a relatively large number (greater than the average of ϳ7 per bacterial genome [38]) of MarR family proteins. A correlation between large genome size and a greater number of transcriptional regulators is a general feature and a common characteristic of bacteria with a more complex lifestyle that may require responses to environmental changes (41).…”

Section: Marr Proteins In Burkholderia Speciesmentioning

confidence: 99%

“…In E. coli, HpaR was shown to repress both the hpa operon as well as its own expression (85). Indeed, several MarR family proteins for which related aromatics induce the expression of the adjacent catabolic enzymes have been characterized (38). Based on the conservation of the hpa gene locus (Fig.…”

Section: Degradation Of Aromatic Compoundsmentioning

confidence: 99%

See 2 more Smart Citations

MarR Family Transcription Factors from Burkholderia Species: Hidden Clues to Control of Virulence-Associated Genes

Gupta

Pande

Sabrin

et al. 2019

Microbiol Mol Biol Rev

Self Cite

View full text Add to dashboard Cite

SUMMARY Species within the genus Burkholderia exhibit remarkable phenotypic diversity. Genomic plasticity, including genome reduction and horizontal gene transfer, has been correlated with virulence traits in several species. However, the conservation of virulence genes in species otherwise considered to have limited potential for infection suggests that phenotypic diversity may not be explained solely on the basis of genetic diversity. Instead, differential organization and control of gene regulatory networks may underlie many phenotypic differences. In this review, we evaluate how regulation of gene expression by members of the multiple antibiotic resistance regulator (MarR) family of transcription factors may contribute to shaping the physiological diversity of Burkholderia species, with a focus on the clinically relevant human pathogens. All Burkholderia species encode a relatively large number of MarR proteins, a feature common to bacteria that must respond to environmental changes such as those associated with host invasion. However, evolution of gene regulatory networks has likely resulted in orthologous transcription factors controlling disparate sets of genes. Adaptation to, and survival in, diverse habitats, including a human or plant host, is key to the success of Burkholderia species as (opportunistic) pathogens, and recent reports suggest that control of virulence-associated genes by MarR proteins features prominently among the survival strategies employed by these species. We suggest that identification of MarR regulons will contribute significantly to clarification of virulence determinants and phenotypic diversity.

show abstract

Section: Multiple Antibiotic Resistance Regulators (Marr)mentioning

confidence: 99%

Section: Marr Proteins In Burkholderia Speciesmentioning

confidence: 99%

See 1 more Smart Citation

MarR Family Transcription Factors from Burkholderia Species: Hidden Clues to Control of Virulence-Associated Genes

Gupta

Pande

Sabrin

et al. 2019

Microbiol Mol Biol Rev

Self Cite

View full text Add to dashboard Cite

show abstract

“…PcaV is an aTF repressor of the MarR family involved in the genetic regulation of the catabolic genes for protocatechuic acid (PCA) in Streptomyces coelicolor [37,38]. This family of aTFs include examples for the sensing of environmental signals including antibiotics, toxic molecules, reactive species [39] and small molecule metabolites [40]. In contrast to most of the aTFs previously employed in directed evolution studies, relatively less is known about the allosteric mechanism of the MarR aTFs [41,42].…”

Section: Introductionmentioning

confidence: 99%

Directed evolution of the PcaV allosteric transcription factor to generate a biosensor for aromatic aldehydes

Machado

Currin

Dixon

2019

Preprint

View full text Add to dashboard Cite

Background:Genetically encoded biosensors are useful tools for the detection of metabolites and industrially valuable molecules, and present many potential applications in biotechnology and biomedicine. However, the most common approach to develop biosensors relies on employing a limited set of naturally occurring allosteric transcript factors (aTFs). Therefore, altering the substrate specificity of aTFs towards the detection of new effectors is an important goal. Results:Here, the PcaV repressor, a member of the MarR aTF family, was used to develop a biosensor for the detection of hydroxyl-substituted benzoic acids, including protocatechuic acid (PCA). The PCA biosensor was further subjected to directed evolution to alter its substrate specificity towards vanillin and other closely related aromatic aldehydes, to generate the Van2 biosensor. Substrate recognition of Van2 was explored in vitro using a range of biochemical and biophysical analyses, and extensive in vivo genetic-phenotypic analysis was performed to determine the role of each amino acid change upon biosensor performance. Conclusions:This is the first study to report directed evolution of a member of the MarR aTF family, and demonstrates the plasticity of the PCA biosensor by altering its substrate specificity to generate a biosensor for aromatic aldehydes.

show abstract

“…The MarR family is an ancient family of TFs, predating the divergence of archaea and bacteria (6). It has undergone extensive gene duplication events, with recent estimates suggesting that bacteria encode an average of seven MarR TFs per genome (7). MarR TFs typically function as environmentally-responsive repressors of genes encoding efflux pumps that export xenobiotics, including many antimicrobial agents, and are defined by the presence of a winged helix-turn-helix (wHTH) DNA-binding domain (8).…”

Section: Introductionmentioning

confidence: 99%

The Evolution of SlyA/RovA Transcription Factors From Repressors to Counter-Silencers inEnterobacteriaceae

Will

Brzović

Trong

et al. 2018

Preprint

View full text Add to dashboard Cite

31Gene duplication and subsequent evolutionary divergence have allowed conserved proteins 32 to develop unique roles. The MarR family of transcription factors (TFs) has undergone extensive 33 duplication and diversification in bacteria, where they act as environmentally-responsive 34 repressors of genes encoding efflux pumps that confer resistance to xenobiotics, including many 35 antimicrobial agents. We have performed structural, functional, and genetic analyses of 36 representative members of the SlyA/RovA lineage of MarR TFs, which retain some ancestral 37 functions, including repression of their own expression and that of divergently-transcribed multi-38 drug efflux pumps, as well as allosteric inhibition by aromatic carboxylate compounds. However, 39 SlyA and RovA have acquired the ability to counter-silence horizontally-acquired genes, which 40 has greatly facilitated the evolution of Enterobacteriaceae by horizontal gene transfer. 41 SlyA/RovA TFs in different species have independently evolved novel regulatory circuits to 42 provide the enhanced levels of expression required for their new role. Moreover, in contrast to 43 MarR, SlyA is not responsive to copper. These observations demonstrate the ability of TFs to 44 acquire new functions as a result of evolutionary divergence of both cis-regulatory sequences and 45 in trans interactions with modulatory ligands.46 Evolution of SlyA Transcription Factors Will, et al. 109been conserved not due to their primordial role in regulating antimicrobial resistance but rather as 110 a consequence of their counter-silencing function, which is essential to maintain the regulated 111 expression of horizontally-acquired genes in Enterobacteriaceae. 112 113 Results 114 Evolution of SlyA Transcription Factors Will, et al. 6 Salicylate-mediated inhibition of SlyA activity. As environmentally-responsive repressors 115 whose conformation and regulatory actions are modulated by small aromatic carboxylates (12, 116 14), MarR family TFs are inhibited by salicylate in vitro (12). In their structural analyses of SlyA-117 DNA interactions, Dolan et al, (33) inferred from our structural data (see below) that salicylate 118 might regulate SlyA. Using electrophoretic mobility shift assays, they demonstrated that salicylate 119 inhibits DNA-binding by SlyA. To confirm that this influences the function of SlyA as a 120 transcriptional regulator, we performed in vitro transcription assays (IVTs) of slyA and the 121 divergently transcribed ydhIJK efflux pump operon. Supercoiled plasmid DNA containing the 122 slyA-ydhIJK region was incubated with RNA polymerase (RNAP) and increasing SlyA 123 concentrations in the presence or absence of salicylate. SlyA repressed slyA transcription 124 approximately 5.3-fold, while ydhI transcription was inhibited ~19-fold (Figure 1A, B). The 125 addition of 2mM sodium salicylate reduced SlyA-mediated repression to 2.8-fold and 3.2-fold, 126 respectively, indicating that the sensitivity to aromatic carboxylates observed in classical MarR 127TFs...

show abstract

Regulation of Metabolic Pathways by MarR Family Transcription Factors

Cited by 67 publications

References 49 publications

MarR Family Transcription Factors from Burkholderia Species: Hidden Clues to Control of Virulence-Associated Genes

MarR Family Transcription Factors from Burkholderia Species: Hidden Clues to Control of Virulence-Associated Genes

Directed evolution of the PcaV allosteric transcription factor to generate a biosensor for aromatic aldehydes

The Evolution of SlyA/RovA Transcription Factors From Repressors to Counter-Silencers inEnterobacteriaceae

Contact Info

Product

Resources

About