Abstract
Nicotinamide (NAM) has a long history in clinical applications and can be safely used for treating various diseases. In recent years, NAM was found to exhibit antimicrobial activities, inhibiting the growth of Plasmodium falciparum, Mycobacterium tuberculosis, and human immunodeficiency virus (HIV). Here we investigated the activity of NAM against Candida albicans, one of the most prevalent human fungal pathogens. Our results showed that NAM exhibited significant antifungal activity against C. albicans, including fluconazole-resistant isolates. NAM could also effectively suppress biofilm formation. In addition, NAM exhibited antifungal activity against non-Candida albicans species and Cryptococcus neoformans. Combination of NAM and fluconazole showed an even strong antifungal activity. The antifungal activity of NAM was further confirmed in a mouse model of disseminated candidiasis. Confocal laser scanning microscopy revealed that NAM increased cell wall β-glucans exposure and chitin content while decreased mannan level. Furthermore, by screening the C. albicans homozygous deletion mutant library, the C. albicans mutant lacking GIN4, which encodes a septin regulatory protein kinase and is essential for the maintenance of cell wall integrity, was identified to be high sensitive to NAM. These findings suggested that NAM might exhibit antifungal activities through affecting cell wall organization.
Highlights
In recent years, with the increase in the number of immunocompromised individuals such as organ transplant recipients, AIDS patients, and patients receiving chemotherapy, a rise in fungal infection has been observed
Addition of 20 mM NAM resulted in an obvious antifungal activity, as approximately 3 log10 CFU/ml decrease was observed as compared to the control group after 12 h of treatment
Since azole-resistant isolates occur frequently, we investigated the activity of NAM against clinically fluconazole-resistant C. albicans isolates 638, 647, and 663
Summary
With the increase in the number of immunocompromised individuals such as organ transplant recipients, AIDS patients, and patients receiving chemotherapy, a rise in fungal infection has been observed. Candida albicans is one of the most prevalent human fungal pathogens, causing superficial mycoses, invasive mucosal infections and disseminated systemic disease (Ng et al, 2015). The mortality related to C. albicans bloodstream infections is usually estimated to be approximately 40% (Wisplinghoff et al, 2014). The antifungal agents commonly used in clinical practice mainly include azoles, echinocandins and polyenes. There are various therapeutic limitations exist in these antifungal drugs. The broad utilization of fluconazole has led to rapidly emerging drug-resistant isolates. Development of safer and more effective antifungal drugs remains a formidable challenge
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