MarR family proteins are important regulators of clinically relevant antibiotic resistance

Beggs, Grace A.; Brennan, Richard G.; Arshad, Mehreen

doi:10.1002/pro.3769

Cited by 39 publications

(24 citation statements)

References 54 publications

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“…Here, we provide an immediate solution to these problems by constructing minimal biosensors for auxin and SA that were derived from bacterial antibiotic resistance proteins [16][17][18][19][20][21]. By combining structural insights, computer modeling, and microfluidics, we demonstrated our biosensors robustly sense hormone concentration gradients, providing temporal memory or speed and precision depending on the exposure time to hormones.…”

Section: Discussionmentioning

confidence: 99%

“…A quest for immediate solutions to these problems pointed us to the plant-associated microbes. Several of these microbes control response to environmental stresses by sensing and 15 metabolizing phenol and indole-based compounds reminiscent of plant hormones [16,17]. Genes derived from such microbes could be used to create minimal biosensing systems aimed in understanding of timing and precision of cell response to transient changes in phytohormones.…”

Section: Introductionmentioning

confidence: 99%

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Robust frequency-encoded dynamics in a minimal synthetic phytohormone crosstalk

Garcia

Navarrete

Sanchis

et al. 2020

Preprint

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SummaryHow do dynamic hormone inputs translate into speed, and precision of response is one of the most challenging questions of science. To approach this question, we constructed minimal synthetic gene circuits capable of responding to plant hormones auxin and salicylic acid (SA). These circuits integrate bacterial multi antibiotic resistance (Mar) repressors that directly detect phytohormones through a ligand-induced conformational switch. The combination of individual circuits in synthetic auxin-SA crosstalk was sufficient to coordinate responses across the cell population with tunable precision and speed in long-term microfluidics experiments. This antagonistic auxin-SA crosstalk retains temporal memory upon extended exposure to hormones and synchronizes the behavior of individual cells with the environmental clock. Our study shows how dynamic hormone inputs can be translated in robust and precise responses with a minimal assembly of bacterial transcriptional repressors, suggesting an alternative regulatory strategy to known plant hormone signaling systems.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Robust frequency-encoded dynamics in a minimal synthetic phytohormone crosstalk

Garcia

Navarrete

Sanchis

et al. 2020

Preprint

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“…In purple, MarR genes coding for antibiotic responsive transcriptional regulator; in blue, MerR gene coding for mercury resistance transcriptional regulator; in green, multidrug transporter genes; in red, multidrug permease genes; in orange, small multidrug resistance protein; in black, genes that are not involved in antibiotic resistance. These transcriptional regulators may belong to the MarR family, which is widespread across different bacterial species, probably due to horizontal gene transfer (Fiorentino et al, 2011;Beggs et al, 2020). Noteworthy, A. mali FL18 contains in its genome a gene coding for a putative undecaprenyl-diphosphatase BcrC (NCBI Accession Number WP_067849704.1), which might be involved in the bacitracin resistance.…”

Section: Mining Of the Arsenic Resistance Genes In A Mali Fl18 Genomementioning

confidence: 99%

Genomic Insight of Alicyclobacillus mali FL18 Isolated From an Arsenic-Rich Hot Spring

et al. 2021

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Extreme environments are excellent places to find microorganisms capable of tolerating extreme temperature, pH, salinity pressure, and elevated concentration of heavy metals and other toxic compounds. In the last decades, extremophilic microorganisms have been extensively studied since they can be applied in several fields of biotechnology along with their enzymes. In this context, the characterization of heavy metal resistance determinants in thermophilic microorganisms is the starting point for the development of new biosystems and bioprocesses for environmental monitoring and remediation. This work focuses on the isolation and the genomic exploration of a new arsenic-tolerant microorganism, classified as Alicyclobacillus mali FL18. The bacterium was isolated from a hot mud pool of the solfataric terrains in Pisciarelli, a well-known hydrothermally active zone of the Campi Flegrei volcano near Naples in Italy. A. mali FL18 showed a good tolerance to arsenite (MIC value of 41 mM), as well as to other metals such as nickel (MIC 30 mM), cobalt, and mercury (MIC 3 mM and 17 μM, respectively). Signatures of arsenic resistance genes (one arsenate reductase, one arsenite methyltransferase, and several arsenite exporters) were found interspersed in the genome as well as several multidrug resistance efflux transporters that could be involved in the export of drugs and heavy metal ions. Moreover, the strain showed a high resistance to bacitracin and ciprofloxacin, suggesting that the extreme environment has positively selected multiple resistances to different toxic compounds. This work provides, for the first time, insights into the heavy metal tolerance and antibiotic susceptibility of an Alicyclobacillus strain and highlights its putative molecular determinants.

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“…However, there are other transcriptional regulators in bacteria that may detect small concentrations of ROS to trigger a quick response against oxidative stress [30]. The most studied are the MarR-family homologs, which are present in the genomes of many different intracellular pathogens [31]. In addition, new families of thiol-based transcriptional regulators have been recently discovered [32], and some of these are only responsive to specific RONS such as the sodium hypochlorite sensor HypS [33].…”

Section: Antioxidant Systems Of Intracellular Bacterial Pathogensmentioning

confidence: 99%

Oxidative Stress-Generating Antimicrobials, a Novel Strategy to Overcome Antibacterial Resistance

et al. 2020

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Antimicrobial resistance is becoming one of the most important human health issues. Accordingly, the research focused on finding new antibiotherapeutic strategies is again becoming a priority for governments and major funding bodies. The development of treatments based on the generation of oxidative stress with the aim to disrupt the redox defenses of bacterial pathogens is an important strategy that has gained interest in recent years. This approach is allowing the identification of antimicrobials with repurposing potential that could be part of combinatorial chemotherapies designed to treat infections caused by recalcitrant bacterial pathogens. In addition, there have been important advances in the identification of novel plant and bacterial secondary metabolites that may generate oxidative stress as part of their antibacterial mechanism of action. Here, we revised the current status of this emerging field, focusing in particular on novel oxidative stress-generating compounds with the potential to treat infections caused by intracellular bacterial pathogens.

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MarR family proteins are important regulators of clinically relevant antibiotic resistance

Cited by 39 publications

References 54 publications

Robust frequency-encoded dynamics in a minimal synthetic phytohormone crosstalk

Robust frequency-encoded dynamics in a minimal synthetic phytohormone crosstalk

Genomic Insight of Alicyclobacillus mali FL18 Isolated From an Arsenic-Rich Hot Spring

Oxidative Stress-Generating Antimicrobials, a Novel Strategy to Overcome Antibacterial Resistance

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