Related Experiment Video
Updated: Aug 19, 2026
High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity
Published on: November 16, 2016
Differential control of synergistic effect with polyene macrolide antibiotics upon Chinese hamster cells in vitro
Abstract:
An amphotericin B-resistant cell (AMBR-1), which was isolated from aneuploid Chinese hamster cells (V79), was found to show much higher resistance than the parent V79 cells to other polyene antibiotics, such as pentamycin and filipin. To obtain the 50 to 60% inhibition of the control protein synthesis activity by a synergistic combination of fusidic acid and amphotericin B, 50 microgram fusidic acid per ml were combined with 10 microgram amphotericin B in V79 cells, whereas in AMBR cells 50 microgram fusidic acid per ml were combined with 100 microgram polyene antibiotic per ml. Bleomycin (10 microgram/ml), which alone did not affect cellular DNA synthesis, inhibited DNA synthesis of V79 cells by more than 90% of the control activity when combined with only 1 microgram pentamycin per ml, whereas a similar extent of inhibition in AMBR cells was observed by combination with more than 5 microgram pentamycin per ml.
Insights
An amphotericin B-resistant cell line (AMBR-1) exhibits cross-resistance to other polyene antibiotics. This resistant cell line requires higher antibiotic concentrations for similar protein and DNA synthesis inhibition compared to parent V79 cells.
Area of Science:
- Cell Biology
- Pharmacology
- Antimicrobial Resistance
Background:
- The development of resistance to antifungal agents like amphotericin B is a significant clinical challenge.
- Understanding the mechanisms of polyene antibiotic resistance can inform the development of new therapeutic strategies.
Purpose of the Study:
- To characterize the resistance profile of an amphotericin B-resistant cell line (AMBR-1).
- To compare the sensitivity of AMBR-1 cells and parent V79 cells to combinations of antibiotics affecting protein and DNA synthesis.
Main Methods:
- Isolation and characterization of amphotericin B-resistant Chinese hamster V79 cells (AMBR-1).
- Assessment of synergistic effects of fusidic acid with amphotericin B on protein synthesis inhibition.
- Evaluation of bleomycin-induced DNA synthesis inhibition in combination with pentamycin.
Main Results:
- AMBR-1 cells demonstrated significantly higher resistance to pentamycin and filipin compared to V79 cells.
- AMBR-1 cells required 10-fold higher concentrations of polyene antibiotics for synergistic protein synthesis inhibition with fusidic acid.
- AMBR-1 cells showed a 5-fold higher requirement for pentamycin to achieve similar DNA synthesis inhibition by bleomycin.
Conclusions:
- The AMBR-1 cell line exhibits broad cross-resistance to polyene antibiotics.
- Increased polyene antibiotic concentrations are necessary to overcome resistance and achieve comparable cellular inhibition in AMBR-1 cells.
- This study provides insights into cellular mechanisms underlying polyene antibiotic resistance.
