Antifungal activity and potential mechanism of berberine hydrochloride against fluconazole-resistant .

The emergence of resistance to fluconazole in has made the clinical treatment of this microbe difficult. A potential strategy to address this problem involves diminishing fungal resistance to antimicrobial drugs. Berberine hydrochloride (BH), the primary active ingredient of the traditional Chinese medicine (TCM) Coptis, inhibits the growth of fluconazole-resistant through its action on the high-osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway. To examine the effect of BH on the HOG-MAPK pathway to assess the potential molecular mechanism by which BH inhibits fluconazole-resistant . The minimum inhibitory concentration (MIC) of BH to fluconazole-resistant was measured using the broth microdilution approach to determine the concentration of effective drug intervention. Changes in physiological functions regulated by the HOG-MAPK pathway in response to BH treatment were measured, as well as the expression of central signalling pathway genes and key downstream factors by qRT-PCR and Western blotting, respectively. BH inhibited fluconazole-resistant and the sensitivity to fluconazole increased after BH treatment. At a concentration of 256 and 64 μg ml BH may affect key downstream factors that regulate several physiological functions of by upregulating the core genes expression of , , , and in the HOG-MAPK pathway. Upregulation of , the key gene for glycerol synthesis, increased cell osmotic pressure. BH treatment increased the accumulation of reactive oxygen species by upregulating the expression of the key respiratory metabolism gene and downregulating the expression of the superoxide dismutase gene . Furthermore, downregulation of mycelial-specific hindered the morphological transformation of and inhibition of the chitin synthase gene and the β-(1,3) glucan synthase gene impaired cytoderm integrity. BH affects multiple target genes in diminishing the resistance of strains to fluconazole. This effect may be related to the action of BH on the HOG-MAPK pathway.