AAC(6')-Ie-APH(2'')-Ia bifunctional protein

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Ontology	CARD's Antibiotic Resistance Ontology
Accession	ARO:3002597
Synonym(s)	aac(6')-bifunctional aacA-aphD APH(2''), aph(2'')-bifunctional, AAC(6')-APH(2'')
CARD Short Name	AAC6_Ie_APH2_Ia
Definition	AAC(6')-Ie-APH(2'')-Ia is an aminoglycoside acetyltransferase encoded by plasmids and transposons in S. aureus, E. faecalis, E. faecium and Staphylococcus warneri.
AMR Gene Family	aminoglycoside bifunctional resistance protein
Drug Class	aminoglycoside antibiotic
Resistance Mechanism	antibiotic inactivation
Resistomes with Perfect Matches	Anaerostipes hadrus^wgs, Bacillus cereus^gi, Bacteroides fragilis^wgs, Campylobacter coli^g+wgs, Campylobacter jejuni^wgs, Campylobacter upsaliensis^wgs, Campylobacter ureolyticus^wgs, Clostridioides difficile^gi, Clostridium butyricum^wgs, Clostridium perfringens^g+p+wgs+gi, Eggerthella lenta^wgs, Enterobacter hormaechei^wgs, Enterocloster clostridioformis^wgs, Enterococcus avium^p+wgs, Enterococcus faecalis^g+p+wgs+gi, Enterococcus faecium^g+p+wgs+gi, Enterococcus hirae^p+wgs, Erysipelatoclostridium ramosum^wgs, Escherichia coli^wgs, Eubacterium maltosivorans^wgs, Faecalibacterium prausnitzii^wgs, Glaesserella parasuis^g+wgs, Helicobacter pullorum^wgs, Klebsiella aerogenes^wgs, Klebsiella pneumoniae^wgs, Lactococcus garvieae^p+wgs, Ruthenibacterium lactatiformans^wgs, Staphylococcus arlettae^p+wgs, Staphylococcus aureus^g+p+wgs+gi, Staphylococcus capitis^g+p+wgs, Staphylococcus epidermidis^g+p+wgs+gi, Staphylococcus equorum^wgs, Staphylococcus haemolyticus^g+wgs+gi, Staphylococcus hominis^wgs, Staphylococcus lugdunensis^g+wgs, Staphylococcus pasteuri^p, Staphylococcus pseudintermedius^g+wgs+gi, Staphylococcus saprophyticus^g+p+wgs, Staphylococcus schleiferi^g+gi, Staphylococcus warneri^g+wgs, Streptococcus agalactiae^g+wgs, Streptococcus dysgalactiae^g, Streptococcus gallolyticus^wgs, Streptococcus mitis^g, Streptococcus pasteurianus^g+gi, Streptococcus pneumoniae^g+wgs, Streptococcus sanguinis^wgs, Streptococcus suis^g+wgs+gi
Resistomes with Sequence Variants	Anaerostipes hadrus^wgs, Bacillus cereus^gi, Bacteroides fragilis^wgs, Campylobacter coli^g+wgs, Campylobacter jejuni^g+wgs, Campylobacter upsaliensis^wgs, Campylobacter ureolyticus^wgs, Clostridioides difficile^gi, Clostridium butyricum^wgs, Clostridium perfringens^g+p+wgs+gi, Eggerthella lenta^wgs, Enterobacter hormaechei^wgs, Enterocloster clostridioformis^wgs, Enterococcus avium^p+wgs, Enterococcus faecalis^g+p+wgs+gi, Enterococcus faecium^g+p+wgs+gi, Enterococcus hirae^p+wgs, Erysipelatoclostridium ramosum^wgs, Escherichia coli^wgs, Eubacterium maltosivorans^wgs, Faecalibacterium prausnitzii^wgs, Glaesserella parasuis^g+wgs, Helicobacter pullorum^wgs, Klebsiella aerogenes^wgs, Klebsiella pneumoniae^wgs, Lactococcus garvieae^p+wgs, Morganella morganii^p, Ruthenibacterium lactatiformans^wgs, Staphylococcus arlettae^p+wgs, Staphylococcus aureus^g+p+wgs+gi, Staphylococcus capitis^g+p+wgs, Staphylococcus epidermidis^g+p+wgs+gi, Staphylococcus equorum^wgs, Staphylococcus haemolyticus^g+wgs+gi, Staphylococcus hominis^wgs, Staphylococcus lugdunensis^g+wgs, Staphylococcus pasteuri^p, Staphylococcus pseudintermedius^g+wgs+gi, Staphylococcus saprophyticus^g+p+wgs, Staphylococcus schleiferi^g+gi, Staphylococcus warneri^g+wgs, Stenotrophomonas maltophilia^wgs, Streptococcus agalactiae^g+wgs, Streptococcus dysgalactiae^g, Streptococcus gallolyticus^wgs, Streptococcus lutetiensis^wgs, Streptococcus mitis^g, Streptococcus pasteurianus^g+gi, Streptococcus pneumoniae^g+wgs, Streptococcus sanguinis^wgs, Streptococcus suis^g+wgs+gi
Classification	10 ontology terms \| Show + process or component of antibiotic biology or chemistry + mechanism of antibiotic resistance + determinant of antibiotic resistance + antibiotic molecule + antibiotic inactivation [Resistance Mechanism] + antibiotic mixture + antibiotic inactivation enzyme + aminoglycoside antibiotic [Drug Class] + gentamicin [Antibiotic] + aminoglycoside modifying enzyme
Parent Term(s)	10 ontology terms \| Show + confers_resistance_to_antibiotic dibekacin [Antibiotic] + confers_resistance_to_antibiotic amikacin [Antibiotic] + confers_resistance_to_antibiotic sisomicin [Antibiotic] + confers_resistance_to_antibiotic netilmicin [Antibiotic] + confers_resistance_to_antibiotic kanamycin A [Antibiotic] + confers_resistance_to_antibiotic tobramycin [Antibiotic] + confers_resistance_to_antibiotic gentamicin A [Antibiotic] + confers_resistance_to_antibiotic 2'-N-ethylnetilmicin [Antibiotic] + confers_resistance_to_antibiotic 5-episisomicin [Antibiotic] + aminoglycoside bifunctional resistance protein [AMR Gene Family]
Sub-Term(s)	1 ontology terms \| Show + aranorosin [Adjuvant] is_small_molecule_inhibitor_of
Publications	Daigle DM, et al. 1999. Chem Biol 6(2): 99-110. Prodigious substrate specificity of AAC(6')-APH(2), an aminoglycoside antibiotic resistance determinant in enterococci and staphylococci. (PMID 10021417) Rouch DA, et al. 1987. J Gen Microbiol 133(11): 3039-3052. The aacA-aphD gentamicin and kanamycin resistance determinant of Tn4001 from Staphylococcus aureus: expression and nucleotide sequence analysis. (PMID 2833561)

Resistomes

Prevalence of AAC(6')-Ie-APH(2'')-Ia bifunctional protein among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 414 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)

Species	NCBI Chromosome	NCBI Plasmid	NCBI WGS	NCBI GI	GRDI-AMR2
Anaerostipes hadrus	0%	0%	1.72%	0%	0%
Anaerostipes hadrus	0%	0%	1.72%	0%	0%
Bacillus cereus	0%	0%	0%	50%	0%
Bacillus cereus	0%	0%	0%	50%	0%
Bacteroides fragilis	0%	0%	0.27%	0%	0%
Bacteroides fragilis	0%	0%	0.27%	0%	0%
Campylobacter coli	13.04%	0%	3.96%	0%	0%
Campylobacter coli	15.94%	0%	10.91%	0%	0%
Campylobacter jejuni	0%	0%	0.05%	0%	0%
Campylobacter jejuni	0.35%	0%	0.14%	0%	0%
Campylobacter upsaliensis	0%	0%	2.4%	0%	0%
Campylobacter upsaliensis	0%	0%	8.8%	0%	0%
Campylobacter ureolyticus	0%	0%	3.45%	0%	0%
Campylobacter ureolyticus	0%	0%	3.45%	0%	0%
Clostridioides difficile	0%	0%	0%	16.67%	0%
Clostridioides difficile	0%	0%	0%	16.67%	0%
Clostridium butyricum	0%	0%	1.96%	0%	0%
Clostridium butyricum	0%	0%	1.96%	0%	0%
Clostridium perfringens	2.5%	0.97%	2.44%	50%	0%
Clostridium perfringens	2.5%	0.97%	4.16%	50%	0%
Eggerthella lenta	0%	0%	5.21%	0%	0%
Eggerthella lenta	0%	0%	5.21%	0%	0%
Enterobacter hormaechei	0%	0%	0.13%	0%	0%
Enterobacter hormaechei	0%	0%	0.13%	0%	0%
Enterocloster clostridioformis	0%	0%	2.33%	0%	0%
Enterocloster clostridioformis	0%	0%	2.33%	0%	0%
Enterococcus avium	0%	33.33%	10.53%	0%	0%
Enterococcus avium	0%	33.33%	10.53%	0%	0%
Enterococcus faecalis	10.91%	5.17%	23.27%	4.17%	0%
Enterococcus faecalis	11.36%	7.14%	24.25%	4.17%	0%
Enterococcus faecium	2.55%	1.55%	5.84%	7.84%	0%
Enterococcus faecium	2.87%	4.79%	16.97%	9.8%	0%
Enterococcus hirae	0%	2.38%	2.31%	0%	0%
Enterococcus hirae	0%	2.38%	2.31%	0%	0%
Erysipelatoclostridium ramosum	0%	0%	46.51%	0%	0%
Erysipelatoclostridium ramosum	0%	0%	46.51%	0%	0%
Escherichia coli	0%	0%	0.01%	0%	0%
Escherichia coli	0%	0%	0.01%	0%	0%
Eubacterium maltosivorans	0%	0%	33.33%	0%	0%
Eubacterium maltosivorans	0%	0%	33.33%	0%	0%
Faecalibacterium prausnitzii	0%	0%	2.91%	0%	0%
Faecalibacterium prausnitzii	0%	0%	2.91%	0%	0%
Glaesserella parasuis	7.69%	0%	5.13%	0%	0%
Glaesserella parasuis	3.85%	0%	2.05%	0%	0%
Helicobacter pullorum	0%	0%	10.34%	0%	0%
Helicobacter pullorum	0%	0%	6.9%	0%	0%
Klebsiella aerogenes	0%	0%	0.28%	0%	0%
Klebsiella aerogenes	0%	0%	0.28%	0%	0%
Klebsiella pneumoniae	0%	0%	0.03%	0%	0%
Klebsiella pneumoniae	0%	0%	0.03%	0%	0%
Lactococcus garvieae	0%	8.33%	2.22%	0%	0%
Lactococcus garvieae	0%	8.33%	2.22%	0%	0%
Morganella morganii	0%	0%	0%	0%	0%
Morganella morganii	0%	2.5%	0%	0%	0%
Ruthenibacterium lactatiformans	0%	0%	6.67%	0%	0%
Ruthenibacterium lactatiformans	0%	0%	6.67%	0%	0%
Staphylococcus arlettae	0%	8.33%	2.5%	0%	0%
Staphylococcus arlettae	0%	8.33%	2.5%	0%	0%
Staphylococcus aureus	7.24%	2.08%	10.74%	5.44%	0%
Staphylococcus aureus	10.56%	2.6%	15.77%	8.02%	0%
Staphylococcus capitis	10%	5.26%	36.08%	0%	0%
Staphylococcus capitis	10%	5.26%	35.44%	0%	0%
Staphylococcus epidermidis	18.06%	2.88%	21.92%	8.57%	0%
Staphylococcus epidermidis	39.35%	2.88%	26.36%	17.14%	0%
Staphylococcus equorum	0%	0%	3.57%	0%	0%
Staphylococcus equorum	0%	0%	3.57%	0%	0%
Staphylococcus haemolyticus	31.03%	0%	41.54%	6.67%	0%
Staphylococcus haemolyticus	51.72%	0%	46.81%	20%	0%
Staphylococcus hominis	0%	0%	6.34%	0%	0%
Staphylococcus hominis	0%	0%	7.8%	0%	0%
Staphylococcus lugdunensis	5.56%	0%	1.54%	0%	0%
Staphylococcus lugdunensis	5.56%	0%	1.54%	0%	0%
Staphylococcus pasteuri	0%	5.88%	0%	0%	0%
Staphylococcus pasteuri	0%	5.88%	0%	0%	0%
Staphylococcus pseudintermedius	43.33%	0%	46.92%	26.67%	0%
Staphylococcus pseudintermedius	40%	0%	45.64%	26.67%	0%
Staphylococcus saprophyticus	5.88%	2.7%	2.1%	0%	0%
Staphylococcus saprophyticus	5.88%	2.7%	0.7%	0%	0%
Staphylococcus schleiferi	18.18%	0%	0%	50%	0%
Staphylococcus schleiferi	18.18%	0%	0%	50%	0%
Staphylococcus warneri	8.33%	0%	7.38%	0%	0%
Staphylococcus warneri	8.33%	0%	7.38%	0%	0%
Stenotrophomonas maltophilia	0%	0%	0.15%	0%	0%
Stenotrophomonas maltophilia	0%	0%	0%	0%	0%
Streptococcus agalactiae	1.87%	0%	2.51%	0%	0%
Streptococcus agalactiae	1.87%	0%	2.58%	0%	0%
Streptococcus dysgalactiae	2%	0%	0%	0%	0%
Streptococcus dysgalactiae	2%	0%	0%	0%	0%
Streptococcus gallolyticus	0%	0%	9.09%	0%	0%
Streptococcus gallolyticus	0%	0%	9.09%	0%	0%
Streptococcus lutetiensis	0%	0%	0%	0%	0%
Streptococcus lutetiensis	0%	0%	2.04%	0%	0%
Streptococcus mitis	11.11%	0%	0%	0%	0%
Streptococcus mitis	11.11%	0%	0%	0%	0%
Streptococcus pasteurianus	50%	0%	0%	16.67%	0%
Streptococcus pasteurianus	50%	0%	0%	16.67%	0%
Streptococcus pneumoniae	0.97%	0%	0.03%	0%	0%
Streptococcus pneumoniae	0.97%	0%	0.03%	0%	0%
Streptococcus sanguinis	0%	0%	1.03%	0%	0%
Streptococcus sanguinis	0%	0%	1.03%	0%	0%
Streptococcus suis	4.8%	0%	9.5%	16.67%	0%
Streptococcus suis	4.8%	0%	7.5%	16.67%	0%

Show Perfect Only

Detection Models

protein homolog model

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): 900

Protein
DNA

>gb|AAA88548.1|-|AAC(6')-Ie-APH(2'')-Ia bifunctional protein [Staphylococcus aureus]
MNIVENEICIRTLIDDDFPLMLKWLTDERVLEFYGGRDKKYTLESLKKHYTEPWEDEVFRVIIEYNNVPIGYGQIYKMYDELYTDYHYPK
TDEIVYGMDQFIGEPNYWSKGIGTRYIKLIFEFLKKERNANAVILDPHKNNPRAIRAYQKSGFRIIEDLPEHELHEGKKEDCYLMEYRYD
DNATNVKAMKYLIEHYFDNFKVDSIEIIGSGYDSVAYLVNNEYIFKTKFSTNKKKGYAKEKAIYNFLNTNLETNVKIPNIEYSYISDELS
ILGYKEIKGTFLTPEIYSTMSEEEQNLLKRDIASFLRQMHGLDYTDISECTIDNKQNVLEEYILLRETIYNDLTDIEKDYIESFMERLNA
TTVFEGKKCLCHNDFSCNHLLLDGNNRLTGIIDFGDSGIIDEYCDFIYLLEDSEEEIGTNFGEDILRMYGNIDIEKAKEYQDIVEEYYPI
ETIVYGIKNIKQEFIENGRKEIYKRTYKD

>gb|GU565967.1|-|24980-26419|AAC(6')-Ie-APH(2'')-Ia bifunctional protein [Staphylococcus aureus]
ATGAATATAGTTGAAAATGAAATATGTATAAGAACTTTAATAGATGATGATTTTCCTTTGATGTTAAAATGGTTAACTGATGAAAGAGTA
TTAGAATTTTATGGTGGTAGAGATAAAAAATATACATTAGAATCATTAAAAAAACATTATACAGAGCCTTGGGAAGATGAAGTTTTTAGA
GTAATTATTGAATATAACAATGTTCCTATTGGATATGGACAAATATATAAAATGTATGATGAGTTATATACTGATTATCATTATCCAAAA
ACTGATGAGATAGTCTATGGTATGGATCAATTTATAGGAGAGCCAAATTATTGGAGTAAAGGAATTGGTACAAGATATATTAAATTGATT
TTTGAATTTTTGAAAAAAGAAAGAAATGCTAATGCAGTTATTTTAGACCCTCATAAAAATAATCCAAGAGCAATAAGGGCATACCAAAAA
TCTGGTTTTAGAATTATTGAAGATTTGCCAGAACATGAATTACACGAGGGCAAAAAAGAAGATTGTTATTTAATGGAATATAGATATGAT
GATAATGCCACAAATGTTAAGGCAATGAAATATTTAATTGAGCATTACTTTGATAATTTCAAAGTAGATAGTATTGAAATAATCGGTAGT
GGTTATGATAGTGTGGCATATTTAGTTAATAATGAATACATTTTTAAAACAAAATTTAGTACTAATAAGAAAAAAGGTTATGCAAAAGAA
AAAGCAATATATAATTTTTTAAATACAAATTTAGAAACTAATGTAAAAATTCCTAATATTGAATATTCGTATATTAGTGATGAATTATCT
ATACTAGGTTATAAAGAAATTAAAGGAACTTTTTTAACACCAGAAATTTATTCTACTATGTCAGAAGAAGAACAAAATTTGTTAAAACGA
GATATTGCCAGTTTTTTAAGACAAATGCACGGTTTAGATTATACAGATATTAGTGAATGTACTATTGATAATAAACAAAATGTATTAGAA
GAGTATATATTGTTGCGTGAAACTATTTATAATGATTTAACTGATATAGAAAAAGATTATATAGAAAGTTTTATGGAAAGACTAAATGCA
ACAACAGTTTTTGAGGGTAAAAAGTGTTTATGCCATAATGATTTTAGTTGTAATCATCTATTGTTAGATGGCAATAATAGATTAACTGGA
ATAATTGATTTTGGAGATTCTGGAATTATAGATGAATATTGTGATTTTATATACTTACTTGAAGATAGTGAAGAAGAAATAGGAACAAAT
TTTGGAGAAGATATATTAAGAATGTATGGAAATATAGATATTGAGAAAGCAAAAGAATATCAAGATATAGTTGAAGAATATTATCCTATT
GAAACTATTGTTTATGGAATTAAAAATATTAAACAGGAATTTATCGAAAATGGTAGAAAAGAAATTTATAAAAGGACTTATAAAGATTGA

Curator Acknowledgements

Curator	Description	Most Recent Edit

AAC(6')-Ie-APH(2'')-Ia bifunctional protein

Prevalence: protein homolog model (view sequences)

Graph