The search for new bioactive molecules with antifungal properties to combat resistance to classical antifungals represents a great challenge. This study aimed to explore the virulence factors and resistance profile of Candida species isolated from urine samples in Benin and the in vitro efficacy of organic extracts of Cyanthillium cinereum (L.) H.Rob., Lippia multiflora Moldenke and Khaya senegalensis (Desv.) A.Juss. on the growth of these Candida spp. The study focused on Candida strains isolated from urine samples collected from patients admitted to the bacteriological analysis laboratories of hospitals in Southern Benin. The sensitivity of these strains to classical antifungal agents was determined by the simple diffusion method. Their pathogenicity was investigated via several virulence factors (gelatinase, hemolysin, hydrophobicity, adhesin, biofilm and lecithinase). The in vitro efficacy of the aqueous, ethanolic and hydro-ethanolic extracts of the plants on Candida albicans ATCC 90028 and on six clinical strains was evaluated by the method of determination of the inhibition diameters. The results obtained showed that 51 different Candida strains were isolated from the collected urine samples with a respective predominance of Candida albicans (52.94%) and Candida glabrata (17.64%) species. All identified species were sensitive to amphotericin B and nystatin but 20% are resistant to fluconazole and present 15 different resistance profiles. Six different virulence factors were identified with a high frequency of hydrophobicity (96.08%) and adhesin (94.12%). Antifungal tests revealed that at 100 mg/mL the plant extracts were active on the tested strains with better activity for Cyanthilium cinereum and Khaya senegalensis. Cyanthilium cinereum, Khaya senegalensis and Lippia multiflora showed antifungal activity on virulent Candida strains suggesting the possibility to explore them further for the discovery of new antifungal molecules.

Approximately 2.8 million people worldwide are infected with bacteria that are deemed resistant to clinically relevant antibiotics. This accounts for 700,000 deaths every year and represents a major public health threat that has been on the rise for the past two decades. In contrast, the pace of antibiotic discovery to treat these resistant pathogens has significantly decreased. Most antibiotics are complex natural products that were isolated from soil microorganisms during the golden era of antibiotic discovery (1940s to 1960s) employing the “Waksman platform”. After the collapse of this discovery platform, other strategies and approaches emerged, including phenotype- or target-based screenings of large synthetic compound libraries. However, these methods have not resulted in the discovery and/or development of new drugs for clinical use in over 30 years. A better understanding of the structure and function of the molecular components that constitute the bacterial system is of paramount importance to design new strategies to tackle drug-resistant pathogens. Herein, we review the traditional approaches as well as novel strategies to facilitate antibiotic discovery that are chemical biology-focused. These include the design and application of chemical probes that can undergo bioorthogonal reactions, such as copper (I)-catalyzed azide-alkyne cycloadditions (CuAAC). By specifically interacting with bacterial proteins or being incorporated in the microorganism’s metabolism, chemical probes are powerful tools in drug discovery that can help uncover new drug targets and investigate the mechanisms of action and resistance of new antibacterial leads.