mphA

Accession ARO:3000316
Synonym(s)macrolide 2'-phosphotransferase I
CARD Short NamemphA
DefinitionThe mphA gene encodes for resistance enzyme MPH(2')-I which preferentially inactivate 14-membered macrolides (e.g.erythromycin, telithromycin, roxithromycin) over 16-membered macrolides (e.g.tylosin, spiramycin). It phosphorylates macrolides at 2'-OH hydroxyl of desosamine sugar of macrolides in a GTP-dependent manner.
AMR Gene Familymacrolide phosphotransferase (MPH)
Drug Classmacrolide antibiotic
Resistance Mechanismantibiotic inactivation
Resistomes with Perfect MatchesAcinetobacter baumanniiwgs, Aeromonas caviaeg+p+wgs, Aeromonas hydrophilag+p+wgs, Aeromonas veroniig+p+wgs, Bordetella trematumg+gi, Citrobacter amalonaticusp+wgs, Citrobacter freundiig+p+wgs, Citrobacter koserig+p+wgs, Citrobacter portucalensisp+wgs, Citrobacter werkmaniiwgs, Citrobacter youngaep+wgs, Comamonas testosteronip, Cronobacter malonaticuswgs, Cronobacter sakazakiip, Enterobacter asburiaep+wgs, Enterobacter cloacaep+wgs, Enterobacter hormaecheip+wgs, Enterobacter kobeip+wgs, Enterobacter roggenkampiip+wgs, Escherichia albertiip+wgs, Escherichia colig+p+wgs+gi, Escherichia fergusoniip+wgs, Klebsiella aerogenesg+p+wgs, Klebsiella michiganensisg+p+wgs, Klebsiella oxytocap+wgs, Klebsiella pneumoniaeg+p+wgs+gi, Klebsiella quasipneumoniaep+wgs, Leclercia adecarboxylatag+p+wgs, Morganella morganiig+p+wgs+gi, Proteus mirabilisg+p+wgs, Providencia rettgeriwgs, Providencia stuartiip+wgs, Pseudomonas aeruginosag+p+wgs, Pseudomonas putidawgs, Raoultella planticolap+wgs, Salmonella entericag+p+wgs+gi, Serratia marcescensp+wgs, Shigella boydiiwgs, Shigella dysenteriaewgs, Shigella flexnerig+p+wgs, Shigella sonneig+p+wgs+gi, Streptococcus suiswgs, Vibrio choleraep+wgs
Resistomes with Sequence VariantsAcinetobacter baumanniiwgs, Aeromonas caviaeg+p+wgs, Aeromonas hydrophilag+p+wgs, Aeromonas veroniig+p+wgs, Alcaligenes faecalisp, Bordetella trematumg+gi, Citrobacter amalonaticusp+wgs, Citrobacter freundiig+p+wgs, Citrobacter koserig+p+wgs, Citrobacter portucalensisp+wgs, Citrobacter werkmaniiwgs, Citrobacter youngaep+wgs, Comamonas testosteronip, Cronobacter malonaticuswgs, Cronobacter sakazakiip, Enterobacter asburiaep+wgs, Enterobacter cloacaep+wgs, Enterobacter hormaecheip+wgs, Enterobacter kobeip+wgs, Enterobacter roggenkampiip+wgs, Escherichia albertiip+wgs, Escherichia colig+p+wgs+gi, Escherichia fergusoniip+wgs, Klebsiella aerogenesg+p+wgs, Klebsiella michiganensisg+p+wgs, Klebsiella oxytocap+wgs, Klebsiella pneumoniaeg+p+wgs+gi, Klebsiella quasipneumoniaep+wgs, Leclercia adecarboxylatag+p+wgs, Morganella morganiig+p+wgs+gi, Proteus mirabilisg+p+wgs, Providencia rettgerig+wgs, Providencia stuartiip+wgs, Pseudomonas aeruginosag+p+wgs, Pseudomonas putidawgs, Raoultella planticolap+wgs, Salmonella entericag+p+wgs+gi, Serratia marcescensp+wgs, Shewanella putrefaciensp, Shigella boydiiwgs, Shigella dysenteriaewgs, Shigella flexnerig+p+wgs, Shigella sonneig+p+wgs+gi, Streptococcus suiswgs, Vibrio alginolyticuswgs, Vibrio choleraeg+p+wgs, Vibrio fluvialiswgs, Vibrio parahaemolyticuswgs
Classification9 ontology terms | Show
Parent Term(s)8 ontology terms | Show
+ macrolide phosphotransferase (MPH) [AMR Gene Family]
+ confers_resistance_to_antibiotic erythromycin [Antibiotic]
+ confers_resistance_to_antibiotic roxithromycin [Antibiotic]
+ confers_resistance_to_antibiotic telithromycin [Antibiotic]
+ confers_resistance_to_antibiotic clarithromycin [Antibiotic]
+ confers_resistance_to_antibiotic azithromycin [Antibiotic]
+ confers_resistance_to_antibiotic dirithromycin [Antibiotic]
+ confers_resistance_to_antibiotic oleandomycin [Antibiotic]
Publications

Noguchi N, et al. 1995. Antimicrob Agents Chemother 39(10): 2359-2363. Nucleotide sequence and characterization of erythromycin resistance determinant that encodes macrolide 2'-phosphotransferase I in Escherichia coli. (PMID 8619599)

Shakya T and Wright GD. 2010. Antimicrob Agents Chemother 54(5): 1909-1913. Nucleotide selectivity of antibiotic kinases. (PMID 20231391)

Chesneau O, et al. 2007. FEMS Microbiol Lett 269(2): 317-322. Resistance phenotypes conferred by macrolide phosphotransferases. (PMID 17302923)

Pawlowski AC, et al. 2018. Nat Commun 9(1):112 The evolution of substrate discrimination in macrolide antibiotic resistance enzymes. (PMID 29317655)

Resistomes

Prevalence of mphA among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 413 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).

Prevalence: protein homolog model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Acinetobacter baumannii0%0%0.01%0%
Aeromonas caviae25%7.79%10.22%0%
Aeromonas hydrophila10.77%5.19%6.45%0%
Aeromonas veronii12.73%4.62%4.49%0%
Alcaligenes faecalis0%20%0%0%
Bordetella trematum20%0%0%50%
Citrobacter amalonaticus0%25%1.82%0%
Citrobacter freundii1.64%9.85%17.02%0%
Citrobacter koseri6.25%15%3.6%0%
Citrobacter portucalensis0%25%24.32%0%
Citrobacter werkmanii0%0%17.95%0%
Citrobacter youngae0%9.09%12.5%0%
Comamonas testosteroni0%50%0%0%
Cronobacter malonaticus0%0%1.82%0%
Cronobacter sakazakii0%2.56%0%0%
Enterobacter asburiae0%0.83%3.16%0%
Enterobacter cloacae0%1.68%9.58%0%
Enterobacter hormaechei0%3.86%8.07%0%
Enterobacter kobei0%1.38%6.99%0%
Enterobacter roggenkampii0%0.48%1.8%0%
Escherichia albertii0%0.56%0.65%0%
Escherichia coli2.07%4.29%10.46%1.02%
Escherichia fergusonii0%1.07%6.52%0%
Klebsiella aerogenes2%5.43%2.82%0%
Klebsiella michiganensis9.68%12.57%7.18%0%
Klebsiella oxytoca0%2.74%4.62%0%
Klebsiella pneumoniae1.07%5.43%17.44%3.81%
Klebsiella quasipneumoniae0%2.75%8.95%0%
Leclercia adecarboxylata7.14%4.76%2.33%0%
Morganella morganii15.38%10%7.36%23.08%
Proteus mirabilis5.5%6.25%1.82%0%
Providencia rettgeri5.88%0%2.55%0%
Providencia stuartii0%2.27%2.27%0%
Pseudomonas aeruginosa0.46%0.29%0.19%0%
Pseudomonas putida0%0%1.6%0%
Raoultella planticola0%11.63%15.38%0%
Salmonella enterica1.58%3.01%1.08%1.66%
Serratia marcescens0%1.29%0.39%0%
Shewanella putrefaciens0%40%0%0%
Shigella boydii0%0%11.11%0%
Shigella dysenteriae0%0%3.33%0%
Shigella flexneri4%7.63%12.27%0%
Shigella sonnei2.44%5.83%3.8%4.76%
Streptococcus suis0%0%0.05%0%
Vibrio alginolyticus0%0%0.4%0%
Vibrio cholerae0.45%10.53%0.96%0%
Vibrio fluvialis0%0%4%0%
Vibrio parahaemolyticus0%0%0.05%0%
Show Perfect Only


Detection Models

Model Type: protein homolog model

Model Definition: Protein Homolog Models (PHM) detect protein sequences based on their similarity to a curated reference sequence, using curated BLASTP bitscore cut-offs. Protein Homolog Models apply to all genes that confer resistance through their presence in an organism, such as the presence of a beta-lactamase gene on a plasmid. PHMs include a reference sequence and a bitscore cut-off for detection using BLASTP. A Perfect RGI match is 100% identical to the reference protein sequence along its entire length, a Strict RGI match is not identical but the bit-score of the matched sequence is greater than the curated BLASTP bit-score cutoff, Loose RGI matches have a bit-score less than the curated BLASTP bit-score cut-off.

Bit-score Cut-off (blastP): 500


>gb|BAA03776.1|-|mphA [Escherichia coli]
MTVVTTADTSQLYALAARHGLKLHGPLTVNELGLDYRIVIATVDDGRRWVLRIPRRAEVSAKVEPEARVLAMLKNRLPFAVPDWRVANAE
LVAYPMLEDSTAMVIQPGSSTPDWVVPQDSEVFAESFATALAALHAVPISAAVDAGMLIRTPTQARQKVADDVDRVRREFVVNDKRLHRW
QRWLDDDSSWPDFSVVVHGDLYVGHVLIDNTERVSGMIDWSEARVDDPAIDMAAHLMVFGEEGLAKLLLTYEAAGGRVWPRLAHHIAERL
AFGAVTYALFALDSGNEEYLAAAKAQLAAAE


>gb|D16251.1|-|1626-2531|mphA [Escherichia coli]
ATGACCGTAGTCACGACCGCCGATACCTCCCAACTGTACGCACTTGCAGCCCGACATGGGCTCAAGCTCCATGGCCCGCTGACTGTCAAT
GAGCTTGGGCTCGACTATAGGATCGTGATCGCCACCGTCGACGATGGACGTCGGTGGGTGCTGCGCATCCCGCGCCGAGCCGAGGTAAGC
GCGAAGGTCGAACCAGAGGCGCGGGTGCTGGCAATGCTCAAGAATCGCCTGCCGTTCGCGGTGCCGGACTGGCGCGTGGCCAACGCCGAG
CTCGTTGCCTATCCCATGCTCGAAGACTCGACTGCGATGGTCATCCAGCCTGGTTCGTCCACGCCCGACTGGGTCGTGCCGCAGGACTCG
GAGGTCTTCGCGGAGAGCTTCGCGACCGCGCTCGCCGCCCTGCATGCCGTCCCCATTTCCGCCGCCGTGGATGCGGGGATGCTCATCCGT
ACACCGACGCAGGCCCGTCAGAAGGTGGCCGACGACGTTGACCGCGTCCGACGCGAGTTCGTGGTGAACGACAAGCGCCTCCACCGGTGG
CAGCGCTGGCTCGACGACGATTCGTCGTGGCCAGATTTCTCCGTGGTGGTGCATGGCGATCTCTACGTGGGCCATGTGCTCATCGACAAC
ACGGAGCGCGTCAGCGGGATGATCGACTGGAGCGAGGCCCGCGTTGATGACCCTGCCATCGACATGGCCGCGCACCTTATGGTCTTTGGT
GAAGAGGGGCTCGCGAAGCTCCTCCTCACGTATGAAGCGGCCGGTGGCCGGGTGTGGCCGCGGCTCGCCCACCACATCGCGGAGCGCCTT
GCGTTCGGGGCGGTCACCTACGCACTCTTCGCCCTCGACTCGGGTAACGAAGAGTACCTCGCTGCGGCGAAGGCGCAGCTCGCCGCAGCG
GAATGA