Molecule Information

General Information of the Molecule (ID: Mol00786)

• Name: Aminoglycoside 3'-phosphotransferase (A3AP) ,Bacillus circulans
• Synonyms: APH(3')IV; Butirosin resistance protein A; Kanamycin kinase; type IV; Neomycin-kanamycin phosphotransferase type IV; aph; butA
• Molecule Type: Protein
• Gene Name: aphA4
• Sequence:
  MNESTRNWPEELLELLGQTELTVNKIGYSGDHVYHVKEYRGTPAFLKIAPSVWWRTLRPE
  IEALAWLDGKLPVPKILYTAEHGGMDYLLMEALGGKDGSHETIQAKRKLFVKLYAEGLRS
  VHGLDIRECPLSNGLEKKLRDAKRIVDESLVDPADIKEEYDCTPEELYGLLLESKPVTED
  LVFAHGDYCAPNLIIDGEKLSGFIDLGRAGVADRYQDISLAIRSLRHDYGDDRYKALFLE
  LYGLDGLDEDKVRYYIRLDEFF
• Function: Resistance to butirosin and structurally-related aminoglycosides, including kanamycin and amikacin.
• Uniprot ID: KKA4_NIACI

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Bacillaceae
Genus: Niallia
Species: Niallia circulans

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

Ampicillin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Escherichia coli infection [1]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Ampicillin
• Molecule Alteration: Expression; Acquired
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli strain JM103; 83333
• In Vitro Model: Bacillus circulans strain; 1397
• In Vitro Model: Streptomyces lividans strain 66; 1200984
• In Vitro Model: Streptomyces lividans strain M180; 1916
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Semi-quantitative phosphocellulose-paper binding assay method assay
• Mechanism Description: The previous demonstration that the APH gene of B. circulans could be expressed in E.coli. These contained a 5.5kb Hind3-digest insert (pCH4) or a 2.7kb Sal1-digest insert (pCH5) at the corresponding site in pBR322. Both these derivatives expressed ampicillin and ribostamycin resistance in E.coli.

Ribostamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Infection by Bacillus circulans [1]

• Resistant Disease: Infection by Bacillus circulans [ICD-11: 1C4Y.12]
• Resistant Drug: Ribostamycin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli strain JM103; 83333
• In Vitro Model: Bacillus circulans strain; 1397
• In Vitro Model: Streptomyces lividans strain 66; 1200984
• In Vitro Model: Streptomyces lividans strain M180; 1916
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Semi-quantitative phosphocellulose-paper binding assay method assay
• Mechanism Description: We have elucidated the full nucleotide sequence of the aminoglycoside phosphotransferase (APH) gene from Bacillus circulans, which produces the aminoglycoside antibiotic butirosin.

Disease Class: Escherichia coli infection [1]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Ribostamycin
• Molecule Alteration: Expression; Acquired
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli strain JM103; 83333
• In Vitro Model: Bacillus circulans strain; 1397
• In Vitro Model: Streptomyces lividans strain 66; 1200984
• In Vitro Model: Streptomyces lividans strain M180; 1916
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Semi-quantitative phosphocellulose-paper binding assay method assay
• Mechanism Description: The previous demonstration that the APH gene of B. circulans could be expressed in E.coli. These contained a 5.5kb Hind3-digest insert (pCH4) or a 2.7kb Sal1-digest insert (pCH5) at the corresponding site in pBR322. Both these derivatives expressed ampicillin and ribostamycin resistance in E.coli.

Disease Class: Streptomyces lividans infection [1]

• Resistant Disease: Streptomyces lividans infection [ICD-11: 1C43.8]
• Resistant Drug: Ribostamycin
• Molecule Alteration: Expression; Acquired
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli strain JM103; 83333
• In Vitro Model: Bacillus circulans strain; 1397
• In Vitro Model: Streptomyces lividans strain 66; 1200984
• In Vitro Model: Streptomyces lividans strain M180; 1916
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Semi-quantitative phosphocellulose-paper binding assay method assay
• Mechanism Description: In attempts to express the B. circulans APH gene in Strep. lividans 66,the 2.7kb Sal1-digest insert of pCH5 was transferred to the Streptomyces vector SLP1.2 by ligating a mixture of a Sal1-digest of pCH5 (1ug) and a partial digest of SLP1.2 (0.5ug) cut at one or two sites of its three Sal1 sites. After incubation, 51 patches of drug-resistant growth were seen. This demonstrated that the ribostamycin-resistance is linked to the plasmid.

Investigative Drug(s) 1 drug(s) in total

Butirosina

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Infection by Bacillus circulans [1]

• Resistant Disease: Infection by Bacillus circulans [ICD-11: 1C4Y.12]
• Resistant Drug: Butirosina
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli strain JM103; 83333
• In Vitro Model: Bacillus circulans strain; 1397
• In Vitro Model: Streptomyces lividans strain 66; 1200984
• In Vitro Model: Streptomyces lividans strain M180; 1916
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Semi-quantitative phosphocellulose-paper binding assay method assay
• Mechanism Description: We have elucidated the full nucleotide sequence of the aminoglycoside phosphotransferase (APH) gene from Bacillus circulans, which produces the aminoglycoside antibiotic butirosin.

References

• Ref 1: Sequence and interspecies transfer of an aminoglycoside phosphotransferase gene (APH) of Bacillus circulans. Self-defence mechanism in antibiotic-producing organisms. Biochem J. 1986 Jan 15;233(2):383-93. doi: 10.1042/bj2330383.