Outer Membrane Channel Protein TolC Regulates Escherichia coli K12 Sensitivity to Plantaricin BM-1 via the CpxR/CpxA Two-Component Regulatory System

ABSTRACT Efflux pumps function to rid bacteria of xenobiotics, including antibiotics, bile salts, and organic solvents. TolC, which forms an outer membrane channel, is an essential component of several efflux pumps in Escherichia coli. We asked whether TolC has a role during growth in the absence of xenobiotics. Because tolC transcription is activated by three paralogous activators, MarA, SoxS, and Rob, we examined the regulation of these activators in tolC mutants. Using transcriptional fusions, we detected significant upregulation of marRAB and soxS transcription and Rob protein activity in tolC mutants. Three mechanisms could be distinguished: (i) activation of marRAB transcription was independent of marRAB, soxR, and rob functions; (ii) activation of soxS transcription required SoxR, a sensor of oxidants; and (iii) Rob protein was activated posttranscriptionally. This mechanism is similar to the mechanisms of upregulation of marRAB, soxS, and Rob by treatment with certain phenolics, superoxides, and bile salts, respectively. The transcription of other marA/soxS/rob regulon promoters, including tolC itself, was also elevated in tolC mutants. We propose that TolC is involved in the efflux of certain cellular metabolites, not only xenobiotics. As these metabolites accumulate during growth, they trigger the upregulation of MarA, SoxS, and Rob, which in turn upregulate tolC and help rid the bacteria of these metabolites, thereby restoring homeostasis.

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Outer membrane channel protein of an oral pathogen binds human cytokine IL-8

Journal of Oral Microbiology ◽

10.1080/20002297.2017.1325206 ◽

2017 ◽

Vol 9 (sup1) ◽

pp. 1325206

Author(s):

Tuuli Ahlstrand

Keyword(s):

Outer Membrane ◽

Membrane Channel ◽

Oral Pathogen ◽

Channel Protein ◽

Outer Membrane Channel ◽

Human Cytokine

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The Mycobacterium tuberculosis Outer Membrane Channel Protein CpnT Confers Susceptibility to Toxic Molecules

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04222-14 ◽

2015 ◽

Vol 59 (4) ◽

pp. 2328-2336 ◽

Cited By ~ 17

Author(s):

Olga Danilchanka ◽

David Pires ◽

Elsa Anes ◽

Michael Niederweis

Keyword(s):

Mycobacterium Tuberculosis ◽

Membrane Permeability ◽

Nutrient Uptake ◽

Outer Membrane ◽

Membrane Channel ◽

Content Type ◽

Channel Protein ◽

Outer Membrane Channel ◽

Outer Membrane Permeability ◽

Slow Growing

ABSTRACTMycobacterium tuberculosis, the causative agent of tuberculosis, is protected from toxic solutes by an effective outer membrane permeability barrier. Recently, we showed that the outer membrane channel protein CpnT is required for efficient nutrient uptake byM. tuberculosisandMycobacterium bovisBCG. In this study, we found that thecpnTmutant ofM. bovisBCG is more resistant than the wild type to a large number of drugs and antibiotics, including rifampin, ethambutol, clarithromycin, tetracycline, and ampicillin, by 8- to 32-fold. Furthermore, thecpnTmutant ofM. bovisBCG was 100-fold more resistant to nitric oxide, a major bactericidal agent required to controlM. tuberculosisinfections in mice. Thus, CpnT constitutes the first outer membrane susceptibility factor in slow-growing mycobacteria. The dual functions of CpnT in uptake of nutrients and mediating susceptibility to toxic molecules are reflected in macrophage infection experiments: while loss of CpnT was detrimental forM. bovisBCG in macrophages that enable bacterial replication, presumably due to inadequate nutrient uptake, it conferred a survival advantage in macrophages that mount a strong bactericidal response. Importantly, thecpnTgene showed a significantly higher density of nonsynonymous mutations in drug-resistant clinicalM. tuberculosisstrains, indicating that CpnT is under selective pressure in human tuberculosis and/or during chemotherapy. Our results indicate that the CpnT channel constitutes an outer membrane gateway controlling the influx of nutrients and toxic molecules into slow-growing mycobacteria. This study revealed that reducing protein-mediated outer membrane permeability might constitute a new drug resistance mechanism in slow-growing mycobacteria.

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TolC of Escherichia coli Functions as an Outer Membrane Channel

Zentralblatt für Bakteriologie ◽

10.1016/s0934-8840(11)80836-4 ◽

1993 ◽

Vol 278 (2-3) ◽

pp. 187-196 ◽

Cited By ~ 58

Author(s):

Roland Benz ◽

Elke Maier ◽

Ivaylo Gentschev

Keyword(s):

Escherichia Coli ◽

Outer Membrane ◽

Membrane Channel ◽

Outer Membrane Channel

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Molecular dynamics simulation of outer membrane channel protein, maltoporin of E.coli

Seibutsu Butsuri ◽

10.2142/biophys.43.s49_4 ◽

2003 ◽

Vol 43 (supplement) ◽

pp. S49

Author(s):

K. Seki ◽

A. Suenaga ◽

T. Narumi ◽

M. Taiji ◽

C. Danelon ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Outer Membrane ◽

Dynamics Simulation ◽

Membrane Channel ◽

Channel Protein ◽

Outer Membrane Channel

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Function and Expression of an N-Acetylneuraminic Acid-Inducible Outer Membrane Channel in Escherichia coli

Journal of Bacteriology ◽

10.1128/jb.187.6.1959-1965.2005 ◽

2005 ◽

Vol 187 (6) ◽

pp. 1959-1965 ◽

Cited By ~ 48

Author(s):

Guy Condemine ◽

Catherine Berrier ◽

Jacqueline Plumbridge ◽

Alexandre Ghazi

Keyword(s):

Escherichia Coli ◽

Outer Membrane ◽

Structural Genes ◽

Membrane Channel ◽

Positive Potential ◽

E Coli ◽

Acetylneuraminic Acid ◽

Catabolite Activator Protein ◽

Intergenic Regions ◽

Outer Membrane Channel

ABSTRACT The Escherichia coli yjhA (renamed nanC) gene encodes a protein of the KdgM family of outer membrane-specific channels. It is transcribed divergently from fimB, a gene involved in the site-specific inversion of the region controlling transcription of the fimbrial structural genes but is separated from it by one of the largest intergenic regions in E. coli. We show that nanC expression is induced by N-acetylneuraminic acid and modulated by N-acetylglucosamine. This regulation occurs via the NanR and NagC regulators, which also control fimB expression. nanC expression is also activated by the regulators cyclic AMP-catabolite activator protein, OmpR, and CpxR. When the NanC protein was reconstituted into liposomes, it formed channels with a conductance of 450 pS at positive potential and 300 to 400 pS at negative potential in 800 mM KCl. The channels had a weak anionic selectivity. In an ompR background, where the general porins OmpF and OmpC are absent, NanC is required for growth of E. coli on N-acetylneuraminic acid as the sole carbon source. All these results suggest that NanC is an N-acetylneuraminic acid outer membrane channel protein.

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