AI Article Synopsis
- The study investigates how ritonavir (RIT) affects the fungal pathogen Candida albicans, focusing on its drug resistance and related genes SAP2 and ERG11.
- C. albicans strains with different levels of drug resistance showed varying activities and pathogenicity, with cross-resistant strains being the most problematic, while RIT alone did not enhance the effects of fluconazole (FCA).
- Results indicate that SAP2 and ERG11 were expressed more in resistant strains, and there were no mutations in SAP2, while ERG11 had several mutations; the findings could help develop new treatments for C. albicans infections.
Article Abstract
Background: Candida albicans, the main human fungal pathogen, can cause fungal infection and seriously affect people's health and life. This study aimed to investigate the effects of ritonavir (RIT) on C. albicans and the correlation between SAP2 as well as ERG11 and drug resistance.
Results: Secreted aspartyl proteinases (Saps) activities and pathogenicity of C. albicans with different drug resistance were measured. M27-A4 broth microdilution method was used to analyze the drug sensitivity of RIT combined with fluconazole (FCA) on C. albicans. After that, SAP2 and ERG11 mutations were examined by polymerase chain reaction (PCR) and sequencing, and quantitative real-time PCR was utilized to determine the expression of the two genes. By analyzing pz values, the Saps activity of cross-resistant strains was the highest, followed by voriconazole (VRC)-resistant strains, FCA-resistant strains, itraconazole (ITR)-resistant strains, and sensitive strains. The pathogenicity of C. albicans in descending order was as follows: cross-resistant strains, VRC-resistant strains, ITR-resistant strains, FCA-resistant strains, and sensitive strains. With the increase of RIT concentrations, the Saps activity was gradually inhibited. Drug sensitivity results showed that there was no synergistic effect between RIT and FCA. Additionally, no gene mutation sites were found in SAP2 sequencing, and 17 synonymous mutations and 6 missense mutations occurred in ERG11 sequencing. Finally, the expression of SAP2 and ERG11 was significantly higher in the resistant strains compared with the sensitive strains, and there was a positive liner correlation between SAP2 and ERG11 messenger RNA expression (r = .6655, p < .001).
Conclusion: These findings may help to improve our understanding of azole-resistant mechanisms of C. albicans and provide a novel direction for clinical therapeutics of C. albicans infection.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342201 | PMC |
| http://dx.doi.org/10.1002/iid3.415 | DOI Listing |
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