Abstract
C. albicans is the most frequently occurring fungal pathogen, and is becoming an increasing public health problem, especially in the context of increased microbial resistance. This opportunistic pathogen is characterized by a versatility explained mainly by its ability to form complex biofilm structures that lead to enhanced virulence and antibiotic resistance. In this context, a review of the known C. albicans biofilm formation inhibitors were performed and a new N-(oxazolylmethyl)-thiazolidinedione scaffold was constructed. 16 new compounds were synthesized and characterized in order to confirm their proposed structures. A general antimicrobial screening against Gram-positive and Gram-negative bacteria, as well as fungi, was performed and revealed that the compounds do not have direct antimicrobial activity. The anti-biofilm activity evaluation confirmed the compounds act as selective inhibitors of C. albicans biofilm formation. In an effort to substantiate this biologic profile, we used in silico investigations which suggest that the compounds could act by binding, and thus obstructing the functions of, the C. albicans Als surface proteins, especially Als1, Als3, Als5 and Als6. Considering the well documented role of Als1 and Als3 in biofilm formation, our new class of compounds that target these proteins could represent a new approach in C. albicans infection prevention and management.
Highlights
Candida spp. are normally commensals found in the gastrointestinal tract, genitourinary tract or oropharyngeal tract of healthy people, but can become opportunistic pathogens that cause superficial infections, deep-seated infections or systemic infections
Due to the specificity against C. albicans biofilm formation, we investigated the affinity that our molecules could have against the agglutinin-like sequence proteins family (Als) family proteins, which are known to be key elements in Candida spp. adhesion, biofilm formation and virulence
In an effort to obtain new agents that target C. albicans biofilm development, following an extensive review of the literature, we proposed a new molecular scaffold: N-(oxazolylmethyl)-thiazolidindione
Summary
Candida spp. are normally commensals found in the gastrointestinal tract, genitourinary tract or oropharyngeal tract of healthy people, but can become opportunistic pathogens that cause superficial infections (oral or vaginal candidiasis), deep-seated infections or systemic infections. The pathogenic potential of this microbial strain is explained by its ability to adapt to various habitats and to form surface-attached microbial communities (biofilms) [3]. Biofilm formation on tissues surfaces leads to superficial infections, while the presence of biofilm on inert substrates, such as medical devices, is directly linked with systemic infections [4,5,6,7,8]. Biofilm-forming ability is associated with persistent candidemia [8] and with an increased risk of mortality in patients with C. albicans bloodstream infections [9]. Biofilm formation is a central element in the acquisition of fungal resistance [10,11]
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