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Published on: September 12, 2019
Inhibitory Effects of Berberine Hydrochloride on Trichophyton mentagrophytes and the Underlying Mechanisms
Chen Wen Xiao1, Yan Liu2, Qiang Wei3
1Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China. xiaochenwen@zaas.ac.cn.
Background:
T. mentagrophytes can infect all mammals, including rabbits, causing serious infections with remarkable economic losses for rabbit farmers. Berberine is an alkaloid that is effective against a variety of microbial infections such as T. mentagrophytes. Growth curve by dry weight determination and in-vivo antifungal assay were carried out to clarify the inhibitory effect of berberine hydrochloride against T. mentagrophytes. Transcriptomics analyses were also carried out for better understanding of the underlying mechanisms.
Results:
The growth rate of T. mentagrophytes was significantly higher in control condition than under berberine hydrochloride or clotrimazole for 60 h. The growth rate of T. mentagrophytes was significantly slighter higher in berberine condition (1 mg) than under clotrimazole for 46 h. T. mentagrophytes seriously shrunk after berberine or clotrimazole treatment, as observed by TEM and in SEM. Significant recovery was evident in three berberine groups on day 6 compared with the DMSO group. Results from transcriptomics analyses showed 18,881 identified unigenes, including 18,754 and 12,127 in the NT and SwissProt databases. Among these, 12,011, 9174, and 11,679 unigenes belonged to 3 Gene Ontology (GO), 43 KEGG, and 25 KOG categories, respectively. Interestingly, we found that down-regulation of 14α-demethylase exposed to various medicines was slightly different, i.e., berberine hydrochloride (fold change -3.4956) and clotrimazole (fold change -2.1283) caused various degrees of alteration.
Conclusions:
Berberine hydrochloride could inhibit the growth of T. mentagrophytes. Berberine hydrochloride could also cure dermatosis induced by T. mentagrophytes. Down-regulation of 14α-demethylase exposed to various medicines was slightly different and might be one of the anti-resistance mechanisms of berberine hydrochloride in T. mentagrophytes. The present investigation provides considerable transcript sequence data that would help further assess the antifungal mechanisms against T. mentagrophytes, for antifungal medicine development.
Insights
Berberine hydrochloride effectively inhibits Trichophyton mentagrophytes growth and treats associated dermatosis in rabbits. This study reveals its antifungal mechanisms, including down-regulation of 14α-demethylase, aiding new antifungal drug development.
Area of Science:
- Mycology
- Pharmacology
- Molecular Biology
Background:
- *Trichophyton mentagrophytes* infections cause significant economic losses in rabbit farming.
- Berberine, a natural alkaloid, exhibits antimicrobial properties against various pathogens, including *T. mentagrophytes*.
Purpose of the Study:
- To investigate the inhibitory effect of berberine hydrochloride on *T. mentagrophytes* growth.
- To elucidate the underlying antifungal mechanisms of berberine hydrochloride through transcriptomics analysis.
Main Methods:
- Growth curve analysis by dry weight determination.
- In-vivo antifungal assay and scanning electron microscopy (SEM) / transmission electron microscopy (TEM) for morphological changes.
- Transcriptomics analysis (unigene identification, Gene Ontology, KEGG, KOG categorization) and gene expression analysis (14α-demethylase).
Main Results:
- Berberine hydrochloride significantly inhibited *T. mentagrophytes* growth compared to control and showed comparable efficacy to clotrimazole.
- *T. mentagrophytes* exhibited significant shrinkage after berberine or clotrimazole treatment.
- Transcriptomics revealed alterations in gene expression, notably the down-regulation of 14α-demethylase by berberine hydrochloride (fold change -3.4956).
Conclusions:
- Berberine hydrochloride effectively inhibits *T. mentagrophytes* growth and cures dermatosis in rabbits.
- Down-regulation of 14α-demethylase is a potential antifungal mechanism of berberine hydrochloride, possibly contributing to overcoming resistance.
- The study provides valuable transcriptomic data for developing novel antifungal therapies against *T. mentagrophytes*.
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