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The TetR Family of Regulators

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TLDR
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.
Abstract
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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The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

TL;DR: This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps, with particular focus on AcrAB-TolC and Mex pumps.
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“Deadman” and “Passcode” microbial kill switches for bacterial containment

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The Cell Wall Lipid PDIM Contributes to Phagosomal Escape and Host Cell Exit of Mycobacterium tuberculosis.

TL;DR: A loss-of-function genetic approach showed that PDIM levels directly correlate with the capacity of M. tuberculosis to escape the phagosome and induce host cell necrosis and macroautophagy, and a novel role of the cell wall lipid PDIM in intracellular host cell modulation, which is important for host cell exit and dissemination of M tuberculosis.
References
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Journal ArticleDOI

Sampling the Antibiotic Resistome

TL;DR: This work has shown that soil-dwelling bacteria are a reservoir of resistance determinants that can be mobilized into the microbial community, and study of this reservoir could provide an early warning system for future clinically relevant antibiotic resistance mechanisms.
Journal ArticleDOI

Efflux-Mediated Drug Resistance in Bacteria

TL;DR: Fluoroquinolones and β-lactams of the latest generations are likely to select for overproduction mutants of these pumps and make the bacteria resistant in one step to practically all classes of antibacterial agents.
Journal ArticleDOI

The TetR Family of Transcriptional Repressors

TL;DR: A general profile for the proteins of the TetR family of repressors is developed, made up of 47 amino acid residues that correspond to the helix-turn-helix DNA binding motif and adjacent regions in the three- dimensional structures of TetR, QacR, CprB, and EthR, four family members for which the function and three-dimensional structure are known.
Journal ArticleDOI

The Small RNA Chaperone Hfq and Multiple Small RNAs Control Quorum Sensing in Vibrio harveyi and Vibrio cholerae

TL;DR: It is proposed that Hfq, together with four candidate sRNAs, creates an ultrasensitive regulatory switch that controls the critical transition into the high cell density, quorum-sensing mode.
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