The underling mechanism of bacterial TetR/AcrR family transcriptional repressors

Deng, Wanyan; Li, Chunmei; Xie, Jianping

doi:10.1016/j.cellsig.2013.04.003

Cited by 122 publications

(95 citation statements)

References 91 publications

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“…Comparison of PR01 through PR06 to the parent revealed that all six polymorphisms were confined to a 50-nucleotide section of a single gene, bas4114, which is annotated as an AcrR transcriptional repressor (Table S11). (54) This particular AcrR protein is predicted to contain a single transmembrane domain near the C -terminus (Figure S11), which is precisely where the PZN-resistance conferring mutations were found, all resulting in premature stop codons. Directly downstream of bas4114 are two EmrE-type multidrug resistance efflux pumps, encoded by bas4115-4116 .…”

Section: Resultsmentioning

confidence: 99%

Plantazolicin Is an Ultranarrow-Spectrum Antibiotic That Targets the Bacillus anthracis Membrane

et al. 2015

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Plantazolicin (PZN) is a ribosomally synthesized and post-translationally modified natural product from Bacillus methylotrophicus FZB42 and Bacillus pumilus. Extensive tailoring to twelve of the fourteen amino acid residues in the mature natural product endows PZN with not only a rigid, polyheterocyclic structure, but also antibacterial activity. Here we report a remarkably discriminatory activity of PZN toward Bacillus anthracis, which rivals a previously-described gamma (γ) phage lysis assay in distinguishing B. anthracis from other members of the Bacillus cereus group. We evaluate the underlying cause of this selective activity by measuring the RNA expression profile of PZN-treated B. anthracis, which revealed significant upregulation of genes within the cell envelope stress response. PZN depolarizes the B. anthracis membrane like other cell envelope-acting compounds but uniquely localizes to distinct foci within the envelope. Selection and whole-genome sequencing of PZN-resistant mutants of B. anthracis implicate a relationship between the action of PZN and cardiolipin (CL) within the membrane. Exogenous CL increases the potency of PZN in wild type B. anthracis and promotes the incorporation of fluorescently tagged PZN in the cell envelope. We propose that PZN localizes to and exacerbates structurally compromised regions of the bacterial membrane, which ultimately results in cell lysis.

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Section: Resultsmentioning

confidence: 99%

Plantazolicin Is an Ultranarrow-Spectrum Antibiotic That Targets the Bacillus anthracis Membrane

et al. 2015

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“…The TetR family of regulators (TFRs) is a large and important family of one-component signal transduction systems (13,14). While members of this family are best known for their roles as regulators of antibiotic efflux pumps, this in fact describes a minority of their functional roles.…”

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The TetR Family of Regulators

Cuthbertson

Nodwell

2013

Microbiol Mol Biol Rev

446

489

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SUMMARY The most common prokaryotic signal transduction mechanisms are the one-component systems in which a single polypeptide contains both a sensory domain and a DNA-binding domain. Among the >20 classes of one-component systems, the TetR family of regulators (TFRs) are widely associated with antibiotic resistance and the regulation of genes encoding small-molecule exporters. However, TFRs play a much broader role, controlling genes involved in metabolism, antibiotic production, quorum sensing, and many other aspects of prokaryotic physiology. There are several well-established model systems for understanding these important proteins, and structural studies have begun to unveil the mechanisms by which they bind DNA and recognize small-molecule ligands. The sequences for more than 200,000 TFRs are available in the public databases, and genomics studies are identifying their target genes. Three-dimensional structures have been solved for close to 200 TFRs. Comparison of these structures reveals a common overall architecture of nine conserved α helices. The most important open question concerning TFR biology is the nature and diversity of their ligands and how these relate to the biochemical processes under their control.

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“…Reguladores transcripcionales TetR fueron identificadas en Achromobacter sp. y están involucrados en el control transcripcional de una multitud de sistemas y vías, incluyendo resistencia a múltiples fármacos, producción de antibióticos, patogenicidad, quórum sensing, estrés osmótico, formación de biopelículas, citocinesis y diversas vías catabólicas (38) .…”

Section: Discussionunclassified

Caracterización molecular de bacterias patógenas de las vías respiratorias de pacientes peruanos con fibrosis quística

Aquino

Gonzáles

Samaniego³

et al. 2017

Rev Peru Med Exp Salud Publica

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The underling mechanism of bacterial TetR/AcrR family transcriptional repressors

Cited by 122 publications

References 91 publications

Plantazolicin Is an Ultranarrow-Spectrum Antibiotic That Targets the Bacillus anthracis Membrane

Plantazolicin Is an Ultranarrow-Spectrum Antibiotic That Targets the Bacillus anthracis Membrane

The TetR Family of Regulators

Caracterización molecular de bacterias patógenas de las vías respiratorias de pacientes peruanos con fibrosis quística

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