Candida albicans antibiofilm molecules: analysis based on inhibition and eradication studies.

Biofilms are communities of microbial cells surrounded by an extracellular polysaccharide matrix, recognized as a fungal source for local and systemic infections and less susceptible to antifungal drugs. Thus, treatment of biofilm-related Candida spp. infections with popular antifungals such as fluconazole is limited and species-dependent and alternatively demands the use of expensive and high toxic drugs. In this sense, molecules with antibiofilm activity have been studied but without care regarding the use of important criteria such as antibiofilm concentration lower than antifungal concentration when considering the process of inhibition of formation and concentrations equal to or lower than 300 µM. Therefore, this review tries to gather the most promising molecules regarding the activity against the C. albicans biofilm described in the last 10 years, considering the activity of inhibition and eradication. From January 2011 to July 2021, articles were searched on Scopus, PubMed, and Science Direct, combining the keywords "antibiofilm," "candida albicans," "compound," and "molecule" with AND and OR operators. After 3 phases of selection, 21 articles describing 42 molecules were discussed in the review. Most of them were more promising for the inhibition of biofilm formation, with SM21 (24) being an interesting molecule for presenting inhibitory and eradication activity in biofilms with 24 and 48 h, as well as alizarin (26) and chrysazine (27), with concentrations well below the antifungal concentration. Despite the detection of these molecules and the attempts to determine the mechanisms of action by microscopic analysis and gene expression, no specific target has been determined. Thus, a gap is signaled, requiring further studies such as proteomic analyses to clarify it.

Upregulation of secreted aspartyl proteinase genes of fluconazole-sensitive Candida albicans isolates.

Candida albicans infection development depends on several factors associated with this etiological agent, including secreted aspartyl protease (Sap) production. Sap expression commonly occurs under selective pressure caused by the presence of antifungals. Fluconazole is the main antifungal drug used for treatment or prophylaxis. This study investigated the influence of inhibitory and sub-inhibitory fluconazole concentrations on Sap activity and their gene transcription for three clinical C. albicans isolates. Two isolates presented significant increases in Sap activity and transcription of SAP 1-8 genes in the presence of 1 MIC80 of fluconazole compared to the absence of the antifungal agent. The results suggest that the increase in Sap activity occurs due to an upregulation of the SAP gene transcription influenced by fluconazole. This suggests the importance of all SAP genes in the progression of bloodstream infections compared to primary tissue infection. However, this phenomenon does not occur everywhere, and it is multifactorial. This may be related to the selective pressure effect on transcription modulators. Although preliminary, these results open a new perspective for the study of virulence factors.