Purification and characterization of macrolide 2'-phosphotransferase from a strain of Escherichia coli that is highly resistant to erythromycin
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MPH(2')I is an inducible intracellular enzyme that is highly active on 14-membered macrolides but shows extremely low activity on 16-membered macrolides — the defining narrow specificity vs MphB.
"MPH(2') is an inducible intracellular enzyme which showed high levels of activity with 14-member-ring macrolides and extremely low levels with 16-member-ring macrolides."
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Purine nucleotides GTP, ITP and ATP serve as phosphate donors.
"Purine nucleotides, such as GTP, ITP, and ATP, were effective as cofactors in the inactivation of macrolides."
Nucleotide sequence and characterization of erythromycin resistance determinant that encodes macrolide 2'-phosphotransferase I in Escherichia coli
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High-level erythromycin resistance from this determinant requires two genes, mphA (encoding MPH(2')I) and mrx (an accessory hydrophobic protein).
"the expression of high-level resistance to erythromycin requires two genes, mphA and mrx, which encode macrolide 2'-phosphotransferase I and an unidentified hydrophobic protein, respectively."
Regulation of transcription of the mph(A) gene for macrolide 2'-phosphotransferase I in Escherichia coli: characterization of the regulatory gene mphR(A)
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MphA synthesis is inducible by erythromycin and is controlled by the regulatory gene mphR(A) — unlike the constitutive MphB.
"The synthesis of macrolide 2'-phosphotransferase I [Mph(A)], which inactivates erythromycin, is inducible by erythromycin."
Resistance phenotypes conferred by macrolide phosphotransferases
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Among the mph genes compared in an efflux-deficient host, mph(A) was uniquely able to confer resistance to azithromycin (a 15-membered macrolide).
"The mph(A) gene was unique in conferring resistance to azithromycin."
Structural Basis for Kinase-Mediated Macrolide Antibiotic Resistance
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Crystal structures of MPH(2')-I (MphA) were determined apo and in complex with GTP analogs and macrolides, revealing the kinase-like fold.
"We present structures for MPH(2')-I and MPH(2')-II in the apo state, and in complex with GTP analogs and six different macrolides."
The evolution of substrate discrimination in macrolide antibiotic resistance enzymes
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MphA is one of the mobilized Mph homologs that are widespread in Gram-negative bacteria.
"MphA, MphB, and MphE are widespread in Gram-negative bacteria"
Look and Outlook on Enzyme-Mediated Macrolide Resistance
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MPH(2')-I (MphA) efficiently inactivates only 14- and 15-membered macrolides, whereas MPH(2')-II (MphB) additionally inactivates 16-membered macrolides and telithromycin — the explicit MphA/MphB contrast.
"MPH(2′)-I can only efficiently inactivate 14- and 15-membered lactone macrolides, whereas MPH(2′)-II can additionally inactivate 16-membered lactone macrolides and the ketolide, telithromycin"
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Mph enzymes transfer the gamma-phosphate of GTP onto macrolide substrates; mph(A), (B) and (C) are mobile-element-encoded and found in clinical E. coli.
"These MPHs all mediate the transfer of the γ-phosphate group from GTP onto the macrolide substrates...mph(A), (B), and (C), which are encoded on mobile genetic elements, are found in clinical isolates of E."
Whole-Genome Sequencing of an Escherichia coli ST69 Strain Harboring bla(CTX-M-27) on a Hybrid Plasmid
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In a clinical E. coli isolate, the mphA-mrx(A)-mphR(A) operon is carried within an IS26/IS6100-bounded composite transposon, the mobile unit that disseminates mphA on IncF plasmids.
"the mphA-mrx(A)-mphR(A) operon conferring macrolide resistance was flanked by IS26 and IS6100, forming the IS26-mphA-mrx(A)-mphR(A)-IS6100 transposable structure"
Multidrug-resistant conjugative plasmid carrying mphA confers increased antimicrobial resistance in Shigella
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A conjugative plasmid carrying mphA transferred high-level azithromycin resistance; all transconjugants reached azithromycin MIC >=256 ug/ml, demonstrating mphA-mediated, plasmid-borne resistance.
"The MIC of azithromycin was ≥ 256 µg/ml for all transconjugants."
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Plasmid-borne mphA inactivates macrolides by modifying the drug's molecular structure.
"Several reports suggested that plasmid-mediated macrolide 2'-phosphotransferase (mphA) mostly and esterase (ermB) for some instances inactivate macrolide through modifying its molecular structure"