Identification and characterization of the new gene rhtA involved in threonine and homoserine efflux in Escherichia coli

Livshits, Vitaliy A.; Zakataeva, Natalia P.; Aleshin, Vladimir V.; Vitushkina, Maria V.

doi:10.1016/s0923-2508(03)00036-6

Cited by 119 publications

(79 citation statements)

References 41 publications

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“…The finding that enhanced mexEF-oprN expression in previously described nfxC mutants and our newly described PA2491 mutants is coupled with reduced production of a basic amino acid-peptide porin, OprD 22), suggests that such metabolites might well be derived from basic amino acids and peptides, whose reduced uptake in such mutants would clearly limit the production of downstream metabolites that might be the substrates for MexEF-OprN and PA2491. Certainly, there is precedence for bacterial efflux of amino acids (6,11,39,71) and their metabolites (11), indicating that under certain circumstances the accumulation of these compounds within the cell is detrimental to cell health.…”

Section: Discussionmentioning

confidence: 99%

Mutations in PA2491 ( mexS ) Promote MexT-Dependent mexEF-oprN Expression and Multidrug Resistance in a Clinical Strain of Pseudomonas aeruginosa

2005

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Disruption of the PA2491 gene in a mini-Tn5-tet insertion mutant of a clinical isolate of Pseudomonas aeruginosa increased expression of the mexEF-oprN multidrug efflux genes and decreased production of outer membrane protein OprD, concomitant with enhanced resistance to chloramphenicol, quinolones, and imipenem, which was reminiscent of previously described nfxC mutants. PA2491 encodes a probable oxidoreductase previously shown to be positively regulated by the MexT positive regulator of mexEF-oprN expression (T. Köhler, S. F. Epp, L. K. Curty, and J. C. Pechére, J. Bacteriol. 181:6300-6305, 1999). Spontaneous multidrugresistant mutants of the P. aeruginosa clinical isolate hyperexpressing mexEF-oprN and showing reduced production of OprD were readily selected in vitro, and all of them were shown to carry mutations in PA2491, highlighting the probable significance of such mutations as determinants of MexEF-OprN-mediated multidrug resistance in vivo.Three-component multidrug efflux systems of the resistancenodulation-division (RND) family are prevalent in gram-negative bacteria, in which they contribute significantly to intrinsic and acquired resistance to a range of clinically important antimicrobial agents (i.e., antibiotics and biocides) (48). In Pseudomonas aeruginosa, an opportunistic human pathogen characterized by an innate resistance to multiple antimicrobial agents (19), seven tripartite RND family efflux systems have been described to date 35,50,51 [25,52,54,64,73] and mexZ [40,69], respectively).The MexEF-OprN system is apparently quiescent in wildtype cells, at least under the usual laboratory growth conditions (32), but it is expressed in nfxC-type multidrug-resistant strains isolated in vitro (14, 32, 42) and in clinics (15,24). nfxC mutants display resistance to fluoroquinolones, chloramphenicol, trimethoprim, and the carbapenem imipenem (14, 32), although resistance to imipenem results not from MexEF-OprN expression (32) but from the concomitant decrease in outer membrane protein OprD in these mutants (14,42). OprD is a basic amino acid-peptide channel and a primary route of entry for carbapenems, such as imipenem, in P. aeruginosa (67, 68), and it is often absent in imipenem-resistant strains of P. aeruginosa (4, 31). In addition to its role in the export of and resistance to antimicrobials, MexEF-OprN also promotes resistance (or tolerance) to organic solvents (36), dyes (16), and biocides, such as triclosan (8). As a result of MexEF-OprN hyperexpression, nfxC mutants also express reduced levels of several quorum-sensing (i.e., homoserine lactone)-dependent extracellular virulence factors (33) and are attenuated for virulence (10), apparently as a result of MexEF-OprN-mediated export of a molecule(s) necessary for homoserine lactone production (33).Unlike the majority of RND-type efflux systems in P. aeruginosa, which are negatively regulated by linked repressor genes, MexEF-OprN expression is positively regulated by the product of the linked mexT gene, a LysR family regulator of mexEFoprN expr...

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Section: Discussionmentioning

confidence: 99%

Mutations in PA2491 ( mexS ) Promote MexT-Dependent mexEF-oprN Expression and Multidrug Resistance in a Clinical Strain of Pseudomonas aeruginosa

2005

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“…Such a role has been proposed for amino acid efflux systems (7). Thus, the Corynebacterium glutamicum LysE lysine effluxer (3,6), ThrE threonine and serine effluxer (40), and BrnFE isoleucine and leucine effluxer (17) and the E. coli RhtA, RhtB, and RhtC threonine effluxers (19,21,53) and ArgO arginine effluxer (26) may serve a role in pumping excess amino acids out to the cell. Similarly, the E. coli EamA (YdeD) (8) and EamB (YfiK) (11) transporters, which efflux cysteine pathway metabolites, may also play a role in ridding the cell of excess metabolites that FIG.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Escherichia coli AaeAB Efflux Pump: a Metabolic Relief Valve?

et al. 2004

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Treatment of Escherichia coli with p-hydroxybenzoic acid (pHBA) resulted in upregulation of yhcP, encoding a protein of the putative efflux protein family. Also upregulated were the adjacent genes yhcQ, encoding a protein of the membrane fusion protein family, and yhcR, encoding a small protein without a known or suggested function. The function of the upstream, divergently transcribed gene yhcS, encoding a regulatory protein of the LysR family, in regulating expression of yhcRQP was shown. Furthermore, it was demonstrated that several aromatic carboxylic acid compounds serve as inducers of yhcRQP expression. The efflux function encoded by yhcP was proven by the hypersensitivity to pHBA of a yhcP mutant strain. A yhcS mutant strain was also hypersensitive to pHBA. Expression of yhcQ and yhcP was necessary and sufficient for suppression of the pHBA hypersensitivity of the yhcS mutant. Only a few aromatic carboxylic acids of hundreds of diverse compounds tested were defined as substrates of the YhcQP efflux pump. Thus, we propose renaming yhcS, yhcR, yhcQ, and yhcP, to reflect their role in aromatic carboxylic acid efflux, to aaeR, aaeX, aaeA, and aaeB, respectively. The role of pHBA in normal E. coli metabolism and the highly regulated expression of the AaeAB efflux system suggests that the physiological role may be as a "metabolic relief valve" to alleviate toxic effects of imbalanced metabolism.

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“…The 751-amino-acid, predicted protein SepJ comprises (i) a 200-residue N-terminal coiled-coil region such as is normally engaged in protein-protein interactions; (ii) an internal, 211-amino-acid sequence that is rich in Pro and Ser and shows similarity to plant extensins and mammalian mucins; and (iii) an ϳ340-amino-acid C-terminal portion that is homologous to proteins in the drug/metabolite exporter (DME) family of Bacteria and Archaea (13), including the RhtA amino acid exporter of Escherichia coli (15) (Fig. 1).…”

Section: Identification Of the Sepj Gene Foxmentioning

confidence: 99%

Septum-Localized Protein Required for Filament Integrity and Diazotrophy in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120

et al. 2007

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Heterocysts, formed when filamentous cyanobacteria, such as Anabaena sp. strain PCC 7120, are grown in the absence of combined nitrogen, are cells that are specialized in fixing atmospheric nitrogen (N 2 ) under oxic conditions and that transfer fixed nitrogen to the vegetative cells of the filament. Anabaena sp. mutants whose sepJ gene (open reading frame alr2338 of the Anabaena sp. genome) was affected showed filament fragmentation and arrested heterocyst differentiation at an early stage. In a sepJ insertional mutant, a layer similar to a heterocyst polysaccharide layer was formed, but the heterocyst-specific glycolipids were not synthesized. The sepJ mutant did not exhibit nitrogenase activity even when assayed under anoxic conditions. In contrast to proheterocysts produced in the wild type, those produced in the sepJ mutant still divided. SepJ is a multidomain protein whose N-terminal region is predicted to be periplasmic and whose C-terminal domain resembles an export permease. Using a green fluorescent protein translationally fused to the carboxyl terminus of SepJ, we observed that in mature heterocysts and vegetative cells, the protein is localized at the intercellular septa, and when cell division starts, it is localized in a ring whose position is similar to that of a Z ring. SepJ is a novel composite protein needed for filament integrity, proper heterocyst development, and diazotrophic growth.

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Identification and characterization of the new gene rhtA involved in threonine and homoserine efflux in Escherichia coli

Cited by 119 publications

References 41 publications

Mutations in PA2491 ( mexS ) Promote MexT-Dependent mexEF-oprN Expression and Multidrug Resistance in a Clinical Strain of Pseudomonas aeruginosa

Mutations in PA2491 ( mexS ) Promote MexT-Dependent mexEF-oprN Expression and Multidrug Resistance in a Clinical Strain of Pseudomonas aeruginosa

Characterization of the Escherichia coli AaeAB Efflux Pump: a Metabolic Relief Valve?

Septum-Localized Protein Required for Filament Integrity and Diazotrophy in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120

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