Naftifine Hydrochloride

Naftifine hydrochloride blocks carotenoid pigment biosynthesis in Staphylococcus aureus through competitive inhibition of diapophytoene desaturase (CrtN), an essential enzyme for carotenoid synthesis in the bacterium. This inhibition occurs at nanomolar concentrations and effectively attenuates the virulence of various clinical S. aureus isolates, including methicillin-resistant S. aureus strains.
Carotenoid pigment serves as a critical virulence factor in S. aureus by shielding the bacterium from host oxidant killing. When naftifine suppresses pigment production, the bacterium becomes more susceptible to host immune clearance. In mouse infection models, naftifine treatment significantly reduced bacterial virulence and improved infection outcomes. These findings reveal that naftifine hydrochloride targets the bacterial enzyme CrtN rather than its classical fungal target squalene epoxidase, representing a previously unrecognized mechanism of action for this drug and providing proof that CrtN is a druggable target against S. aureus infections.

Fig. 1 Naftifine has antivirulence properties against S. aureus Newman. (Chen F.; et al. 2016)