Drug Information

Drug (ID: DG00119) and It's Reported Resistant Information

• Name: Ribostamycin
• Synonyms: Ribostamycin; Vistamycin; Hetangmycin; Xylostatin; Antibiotic SF 733; Ribostamycinum; Ribostamicina; Ribostamycine; Ribastamin; Dekamycin IV; SF 733; 25546-65-0; ribostamycin A; Ribostamycin [INN:BAN]; Bu 1709; Ribostamycine [INN-French]; Ribostamycinum [INN-Latin]; UNII-2Q5JOU7T53; SF-733; Ribostamicina [INN-Spanish]; C17H34N4O10; EINECS 247-091-5; NSC 138925; BRN 1357280; 2Q5JOU7T53; CHEBI:45257; NSC138925; O-2,6-Diamino-2,6-dideoxy-alpha-D-glucopyranosyl-(1->4)-O-(beta-D-ribofuranosyl-(1->5))-2-deoxystreptamine
• Indication:
  In total 1 Indication(s)
  Discovery agent [ICD-11: N.A.]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (5 diseases)
  Actinomycetoma [ICD-11: 1C43]; [2]
  Bacillus infection [ICD-11: 1C4Y]; [1]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [3]
  Escherichia coli intestinal infection [ICD-11: 1A03]; [1]
  Pneumonia [ICD-11: CA40]; [3]
• Target: Bacterial 16S ribosomal RNA (Bact 16S rRNA); NOUNIPROTAC; [1]
• Formula: C17H34N4O10
• IsoSMILES: C1[C@H]([C@@H]([C@H]([C@@H]([C@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CN)O)O)N)O[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O)O)O)N
• InChI: 1S/C17H34N4O10/c18-2-6-10(24)12(26)8(21)16(28-6)30-14-5(20)1-4(19)9(23)15(14)31-17-13(27)11(25)7(3-22)29-17/h4-17,22-27H,1-3,18-21H2/t4-,5+,6-,7-,8-,9+,10-,11-,12-,13-,14-,15-,16-,17+/m1/s1
• InChIKey: NSKGQURZWSPSBC-VVPCINPTSA-N
• PubChem CID: 33042
• ChEBI ID: CHEBI:45257
• TTD Drug ID: D08PVY
• DrugBank ID: DB03615

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Serratia marcescens infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• In Vitro Model: Escherichia coli strain 83-125; 562
• In Vitro Model: Escherichia coli strain 83-75; 562
• In Vitro Model: Escherichia coli strain JM83; 562
• In Vitro Model: Escherichia coli strain JM83(pRPG101); 562
• In Vitro Model: Escherichia coli strain M8820Mu; 562
• In Vitro Model: Escherichia coli strain MC1065; 562
• In Vitro Model: Escherichia coli strain MC1065(pRPG101); 562
• In Vitro Model: Escherichia coli strain POII1681; 562
• In Vitro Model: Escherichia coli strain PRC930(pAO43::Tn9O3); 562
• In Vitro Model: Klebsiella pneumoniae strains; 573
• In Vitro Model: Serratia marcescens strains; 615
• Experiment for Molecule Alteration: Restriction enzyme treating assay
• Experiment for Drug Resistance: Cation-supplemented Mueller-Hinton broth assay; agar dilution with MH agar assay
• Mechanism Description: Clinical isolates of Klebsiella pneumoniae and Serratia marcescens at a hospital that had used amikacin as its principal aminoglycoside for the preceding 42 months demonstrated high-level resistance to amikacin (greater than or equal to 256 micrograms/ml), kanamycin (greater than or equal to 256 micrograms/ml), gentamicin (greater than or equal to 64 micrograms/ml), netilmicin (64 micrograms/ml), and tobramycin (greater than or equal to 16 micrograms/ml). The clinical isolates and transformants produced a novel 3'-phosphotransferase, APH(3'), that modified amikacin and kanamycin in vitro.

Escherichia coli intestinal infection [ICD-11: 1A03]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [1]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• 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.

Actinomycetoma [ICD-11: 1C43]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [1]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Streptomyces lividans infection [ICD-11: 1C43.8]
• 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.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [2]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptomyces ribosidificus infection [ICD-11: 1C43.14]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptomyces lividans strain 66; 1200984
• In Vitro Model: Escherichia coli strain DH-SCY; 562
• In Vitro Model: Escherichia coli strain k-12; 83333
• In Vitro Model: Streptomyces hygroscopicus strain SF1084; 1912
• In Vitro Model: Streptomyces ribosidificus strain SF733; 80859
• Experiment for Molecule Alteration: Northern hybridization assay
• Experiment for Drug Resistance: Gradient-plate technique of Szybalski assay
• Mechanism Description: The rph gene conferring ribostamycin 3'-O-phosphorylation was isolated from a ribostamycin producer, S. ribosidifcus SF733.

Bacillus infection [ICD-11: 1C4Y]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [1]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Infection by Bacillus circulans [ICD-11: 1C4Y.12]
• 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.

ICD-12: Respiratory system diseases

Pneumonia [ICD-11: CA40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Klebsiella pneumoniae infection [ICD-11: CA40.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• In Vitro Model: Escherichia coli strain 83-125; 562
• In Vitro Model: Escherichia coli strain 83-75; 562
• In Vitro Model: Escherichia coli strain JM83; 562
• In Vitro Model: Escherichia coli strain JM83(pRPG101); 562
• In Vitro Model: Escherichia coli strain M8820Mu; 562
• In Vitro Model: Escherichia coli strain MC1065; 562
• In Vitro Model: Escherichia coli strain MC1065(pRPG101); 562
• In Vitro Model: Escherichia coli strain POII1681; 562
• In Vitro Model: Escherichia coli strain PRC930(pAO43::Tn9O3); 562
• In Vitro Model: Klebsiella pneumoniae strains; 573
• In Vitro Model: Serratia marcescens strains; 615
• Experiment for Molecule Alteration: Restriction enzyme treating assay
• Experiment for Drug Resistance: Cation-supplemented Mueller-Hinton broth assay; agar dilution with MH agar assay
• Mechanism Description: Clinical isolates of Klebsiella pneumoniae and Serratia marcescens at a hospital that had used amikacin as its principal aminoglycoside for the preceding 42 months demonstrated high-level resistance to amikacin (greater than or equal to 256 micrograms/ml), kanamycin (greater than or equal to 256 micrograms/ml), gentamicin (greater than or equal to 64 micrograms/ml), netilmicin (64 micrograms/ml), and tobramycin (greater than or equal to 16 micrograms/ml). The clinical isolates and transformants produced a novel 3'-phosphotransferase, APH(3'), that modified amikacin and kanamycin in vitro.

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.
• Ref 2: Nucleotide sequence of the ribostamycin phosphotransferase gene and of its control region in Streptomyces ribosidificus. Gene. 1988 Sep 7;68(2):285-96. doi: 10.1016/0378-1119(88)90031-5.
• Ref 3: Isolation, characterization, and cloning of a plasmid-borne gene encoding a phosphotransferase that confers high-level amikacin resistance in enteric bacilli. Antimicrob Agents Chemother. 1988 Sep;32(9):1379-84. doi: 10.1128/AAC.32.9.1379.