Molecule Information

General Information of the Molecule (ID: Mol00785)

• Name: Aminoglycoside 3'-phosphotransferase (A3AP) ,Acinetobacter baumannii
• Synonyms: APH(3')VI; Kanamycin kinase; type VI; Neomycin-kanamycin phosphotransferase type VI
• Molecule Type: Protein
• Gene Name: aphA-6
• Sequence:
  MELPNIIQQFIGNSVLEPNKIGQSPSDVYSFNRNNETFFLKRSSTLYTETTYSVSREAKM
  LSWLSEKLKVPELIMTFQDEQFEFMITKAINAKPISALFLTDQELLAIYKEALNLLNSIA
  IIDCPFISNIDHRLKESKFFIDNQLLDDIDQDDFDTELWGDHKTYLSLWNELTETRVEER
  LVFSHGDITDSNIFIDKFNEIYFLDLGRAGLADEFVDISFVERCLREDASEETAKIFLKH
  LKNDRPDKRNYFLKLDELN
• Function: Resistance to kanamycin and structurally-related aminoglycosides, including amikacin.
• Uniprot ID: KKA6_ACIBA

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Moraxellales
Family: Moraxellaceae
Genus: Acinetobacter
Species: Acinetobacter baumannii

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Amikacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Acinetobacter baumannii infection [1]

• Resistant Disease: Acinetobacter baumannii infection [ICD-11: CA40.4]
• Resistant Drug: Amikacin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Acinetobacter baumannii strain BM2580; 470
• In Vitro Model: Bacillus subtilis strain BS168; 1423
• Experiment for Molecule Alteration: Amino acid sequence comparison assay
• Mechanism Description: Resistance to aminogiycosides in Aeinetobaeter is widespread and is mainly the result of the production of enzymes which modify the antibiotics. The enzymes beiong to three ciasses: phosphotransferases (APH), acetyltransferases (AAC). A. baumahnii strain BM2580, a representative of one of these epidemics, was shown to synthesize a 3'-aminoglycoside phosphotransferase. Substrate specificity and DNA annealing studies indicated that the isozyme in A. baumannii was of a new type, designated APH(3')-VI.

Disease Class: Escherichia coli infection [1]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Amikacin
• Molecule Alteration: Expression; Acquired
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Acinetobacter baumannii strain BM2580; 470
• In Vitro Model: Bacillus subtilis strain BS168; 1423
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The shuttle piasmid pAT239 was constructed by inserting the H/ndlll-linearized staphyococcal piasmid pC194 into the unique H/ndlll site of pAT235. This piasmid, which confers resistance to ampicillin, chloramphenicol and kanamycin in Escherichia coli, was introduced by transformation into Bacillus subtilis strain BS168.

Kanamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Acinetobacter baumannii infection [1]

• Resistant Disease: Acinetobacter baumannii infection [ICD-11: CA40.4]
• Resistant Drug: Kanamycin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Acinetobacter baumannii strain BM2580; 470
• In Vitro Model: Bacillus subtilis strain BS168; 1423
• Experiment for Molecule Alteration: Amino acid sequence comparison assay
• Mechanism Description: Resistance to aminogiycosides in Aeinetobaeter is widespread and is mainly the result of the production of enzymes which modify the antibiotics. The enzymes beiong to three ciasses: phosphotransferases (APH), acetyltransferases (AAC). A. baumahnii strain BM2580, a representative of one of these epidemics, was shown to synthesize a 3'-aminoglycoside phosphotransferase. Substrate specificity and DNA annealing studies indicated that the isozyme in A. baumannii was of a new type, designated APH(3')-VI.

Disease Class: Escherichia coli infection [1]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Kanamycin
• Molecule Alteration: Expression; Acquired
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Acinetobacter baumannii strain BM2580; 470
• In Vitro Model: Bacillus subtilis strain BS168; 1423
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: Resistance to aminogiycosides in Aeinetobaeter is widespread and is mainly the result of the production of enzymes which modify the antibiotics. The enzymes beiong to three ciasses: phosphotransferases (APH), acetyltransferases (AAC). A. baumahnii strain BM2580, a representative of one of these epidemics, was shown to synthesize a 3'-aminoglycoside phosphotransferase. Substrate specificity and DNA annealing studies indicated that the isozyme in A. baumannii was of a new type, designated APH(3')-VI. Cloning and localization of the kanamyein-resistance determinant Piasmids pAT235 and pAT236, constructed by inserting the 1.8kb Ace\ and 2.1 kb EcoRI fragments of plP1841, respectively, into pUC18, conferred kanamycin resistance to E. coli.

References

• Ref 1: Nucleotide sequence of Acinetobacter baumannii aphA-6 gene: evolutionary and functional implications of sequence homologies with nucleotide-binding proteins, kinases and other aminoglycoside-modifying enzymes. Mol Microbiol. 1988 Sep;2(5):615-25. doi: 10.1111/j.1365-2958.1988.tb00070.x.