Inhibitory effect of proteinase K against dermatophyte biofilms: an alternative for increasing the antifungal effects of terbinafine and griseofulvin

Abstract

This study aimed to evaluate the effect of proteinase K on mature biofilms of dermatophytes, by assays of metabolic activity and biomass. In addition, the proteinase K–terbinafine and proteinase K–griseofulvin interactions against these biofilms were investigated by the checkerboard assay and scanning electron and confocal microscopy. The biofilms exposed to 32 µg ml⁻¹ of proteinase K had lower metabolic activity and biomass, by 39% and 38%, respectively. Drug interactions were synergistic, with proteinase K reducing the minimum inhibitory concentration of antifungals against dermatophyte biofilms at a concentration of 32 µg ml⁻¹ combined with 128–256 µg ml⁻¹ of terbinafine and griseofulvin. Microscopic images showed a reduction in biofilms exposed to proteinase K, proteinase K–terbinafine and proteinase K–griseofulvin combinations. These findings demonstrate that proteinase K has activity against biofilms of dermatophytes, and the interactions of proteinase K with terbinafine and griseofulvin improve the activity of drugs against mature dermatophyte biofilms.

Keywords:

• Dermatophytes
• biofilm
• proteinase K
• antifungals
• synergism

Disclosure statement

There are no potential conflicts of interest.

Additional information

Funding

The Analytical Center UFC/CT-INFRA/MCTI-SISNANO/Pro-Equipment CAPES for technical support to obtain microscopic images. This work was supported by the Brazilian agencies National Council for Scientific and Technological Development (CNPq; grant 305890/2021-2) and Office for the Improvement of Higher Education Personnel (CAPES; Brazil; grant 88881.168799/2018-01).