Drug Information

Drug (ID: DG00265) and It's Reported Resistant Information

• Name: Hygromycin B
• Synonyms: AC1NUSSH
• 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 (1 diseases)
  Escherichia coli intestinal infection [ICD-11: 1A03]; [1]
• Target: Bacterial 16S ribosomal RNA (Bact 16S rRNA); NOUNIPROTAC; [1]
• Target: Bacterial Ribosomal ATPase RbbA (Bact rbbA); RBBA_ECOLI; [1]
• Formula: C20H37N3O13
• IsoSMILES: CN[C@H]1C[C@H]([C@@H]([C@H]([C@@H]1O)O[C@H]2[C@@H]3[C@H]([C@H]([C@H](O2)CO)O)OC4(O3)[C@@H]([C@H]([C@H]([C@H](O4)[C@H](CO)N)O)O)O)O)N
• InChI: 1S/C20H37N3O13/c1-23-7-2-5(21)9(26)15(10(7)27)33-19-17-16(11(28)8(4-25)32-19)35-20(36-17)18(31)13(30)12(29)14(34-20)6(22)3-24/h5-19,23-31H,2-4,21-22H2,1H3/t5-,6+,7+,8-,9+,10-,11+,12-,13+,14-,15-,16+,17+,18-,19+,20 /m1/s1
• InChIKey: GRRNUXAQVGOGFE-HUCHGKBZSA-N
• PubChem CID: 56928061
• TTD Drug ID: D0S6RD
• DrugBank ID: DB11520

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  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 Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Erad and inmad ubiquitin-conjugating enzymes (E2s) [2]

• Sensitive Disease: Lactobacillus casei infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; Rv2043c; p.His57Asp
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Yeast strains; 4751
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: Cell growth rate assay
• Mechanism Description: distorts the ribosome decoding center

Key Molecule: Erad and inmad ubiquitin-conjugating enzymes (E2s) [2]

• Sensitive Disease: Lactobacillus casei infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; Rv2780; c.-32T?>?C
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Yeast strains; 4751
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: Cell growth rate assay
• Mechanism Description: Loss of UBC7 reduces tolerance to multiple transition metals, which oxidatively damage a range of biological macromolecules, including proteins, and genotoxic agents.

Key Molecule: 16S rRNA adenine dimethyltransferase (KsgA) [3]

• Sensitive Disease: Lactobacillus casei infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; A1518/1519
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Pseudomonas aeruginosa strain UCBPP-PA14; 1763
• Experiment for Molecule Alteration: Primer extension analysis; MS analysis; Western blot assay; Semiquantitative RT-PCR
• Experiment for Drug Resistance: Phenotypic microarrays assay; MIC assay; Oxidative stress sensitivity testing; Superoxide dismutase enzyme activity assay
• Mechanism Description: In this study, we demonstrated the absence of A1518/1519 methylation in the 16S rRNA of a Pseudomonas aeruginosa ksgA mutant. Biolog phenotypic microarrays were used to screen the phenotypes of the ksgA mutant against various antimicrobial agents. The loss of ksgA led to increased sensitivity to menadione, a superoxide generator, which was, at least in part, attributed to decreased in a superoxide dismutase (SOD) activity. Interestingly, the decrease in SOD activity in the ksgA mutant was linked to a decrease in the SodM protein levels, but not the sodM mRNA levels. Furthermore, the ksgA mutant strain exhibited sensitivity to hygromycin B and tylosin antibiotics. The tylosin-sensitive phenotype was correlated with decreased transcriptional levels of tufA, tufB, and tsf, which encode elongation factors. Additionally, the ksgA mutant showed resistance to kasugamycin. Collectively, these findings highlight the role of KsgA in oxidative stress responses and antibiotic sensitivity in P. aeruginosa.

Drug Inactivation by Structure Modification (DISM)

Key Molecule: 16S rRNA adenine dimethyltransferase (KsgA) [3]

• Sensitive Disease: Lactobacillus casei infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; A1182V
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Pseudomonas aeruginosa; 1763
• Experiment for Molecule Alteration: PCR; Southern blot assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: SOD enzymatic activity and SodM protein levels are reduced in the ksgA mutant strain;The absence of ksgA contributes to an altered antibiotic response

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]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain BE904; 562
• In Vitro Model: Escherichia coli strain CSR603; 562
• In Vitro Model: Escherichia coli strain DH1; 536056
• In Vitro Model: Escherichia coli strain JA221; 562
• In Vitro Model: Escherichia coli strain k12; 83333
• In Vitro Model: Escherichia coli strain RR1; 562
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: O-galactosidase assay
• Mechanism Description: Hygromycin B resistance is mediated by an aminocyc1ito1 phosphotransferase that inactivates by covalent addition of a phosphate to the 4-position of hygromycin B. The gene is abbreviated as aph(4).

References

• Ref 1: Analysis of a bacterial hygromycin B resistance gene by transcriptional and translational fusions and by DNA sequencing. Nucleic Acids Res. 1983 Oct 11;11(19):6895-911. doi: 10.1093/nar/11.19.6895.
• Ref 2: Endoplasmic reticulum and inner nuclear membrane ubiquitin-conjugating enzymes Ubc6 and Ubc7 confer resistance to hygromycin B in Saccharomyces cerevisiae. MicroPubl Biol. 2024 Jul 29;2024:10.17912/micropub.biology.001276.
• Ref 3: 16S rRNA methyltransferase KsgA contributes to oxidative stress and antibiotic resistance in Pseudomonas aeruginosa. Sci Rep. 2024 Nov 3;14(1):26484.