Disease Information

General Information of the Disease (ID: DIS00573)

• Name: Citrobacter
• ICD: ICD-11: XN0FZ

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

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

Ribostamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Aminoglycoside O-phosphotransferase APH(3')-Ie [1]

• Resistant Disease: citrobacter gillenii infection [ICD-11: XN0FZ]
• Resistant Drug: Ribostamycin
• Molecule Alteration: Expression; Up-regulation
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: Drug susceptibility testing
• Mechanism Description: A novel aminoglycoside resistance gene, designated aph(3')-Ie, which confers resistance to ribostamycin, kanamycin, sisomicin and paromomycin, was identified in the chromosome of the animal bacterium Citrobacter gillenii DW61, which exhibited a multidrug resistance phenotype. APH(3')-Ie showed the highest amino acid identity of 74.90% with the functionally characterized enzyme APH(3')-Ia. Enzyme kinetics analysis demonstrated that it had phosphorylation activity toward four aminoglycoside substrates, exhibiting the highest affinity (K m, 4.22 ± 0.88 uM) and the highest catalytic efficiency [k cat/K m, (32.27 ± 8.14) x 104] for ribomycin. Similar to the other APH(3') proteins, APH(3')-Ie contained all the conserved functional sites of the APH family. The aph(3')-Ie homologous genes were present in C. gillenii isolates from different sources, including some of clinical significance.

References

• Ref 1: APH(3')-Ie, an aminoglycoside-modifying enzyme discovered in a rabbit-derived Citrobacter gillenii isolate. Front Cell Infect Microbiol. 2024 Jul 30;14:1435123.