Although considered rare, the emergent Candida haemulonii species complex, formed by C. haemulonii sensu stricto (Ch), C. duobushaemulonii (Cd) and C. haemulonii var. vulnera (Chv), is highlighted due to its profile of increased resistance to the available antifungal drugs. In the present work, 25 clinical isolates, recovered from human infections during 2011–2020 and biochemically identified by automated system as C. haemulonii, were initially assessed by molecular methods (amplification and sequencing of ITS1-5.8S-ITS2 gene) for precise species identification. Subsequently, the antifungal susceptibility of planktonic cells, biofilm formation and susceptibility of biofilms to antifungal drugs and the secretion of key molecules, such as hydrolytic enzymes, hemolysins and siderophores, were evaluated by classical methodologies. Our results revealed that 7 (28%) isolates were molecularly identified as Ch, 7 (28%) as Chv and 11 (44%) as Cd. Sixteen (64%) fungal isolates were recovered from blood. Regarding the antifungal susceptibility test, the planktonic cells were resistant to (i) fluconazole (100% of Ch and Chv, and 72.7% of Cd isolates), itraconazole and voriconazole (85.7% of Ch and Chv, and 72.7% of Cd isolates); (ii) no breakpoints were defined for posaconazole, but high MICs were observed for 85.7% of Ch and Chv, and 72.7% of Cd isolates; (iii) all isolates were resistant to amphotericin B; and (iv) all isolates were susceptible to echinocandins (except for one isolate of Cd) and to flucytosine (except for two isolates of Cd). Biofilm is a well-known virulence and resistant structure in Candida species, including the C. haemulonii complex. Herein, we showed that all isolates were able to form viable biofilms over a polystyrene surface. Moreover, the mature biofilms formed by the C. haemulonii species complex presented a higher antifungal-resistant profile than their planktonic counterparts. Secreted molecules associated with virulence were also detected in our fungal collection: 100% of the isolates yielded aspartic proteases, hemolysins and siderophores as well as phospholipase (92%), esterase (80%), phytase (80%), and caseinase (76%) activities. Our results reinforce the multidrug resistance profile of the C. haemulonii species complex, including Brazilian clinical isolates, as well as their ability to produce important virulence attributes such as biofilms and different classes of hydrolytic enzymes, hemolysins and siderophores, which typically present a strain-dependent profile.

1,10-Phenanthroline-5,6-dione (phendione) is a functionalized derivative of 1,10-phenanthroline bearing two carbonyl groups at the 5,6-positions, which enhance its electron-accepting ability, polarity and coordination versatility. These structural features enable phendione to act as a bidentate ligand for a variety of transition metals, forming stable coordination compounds (or complexes) widely explored in coordination chemistry, catalysis, materials science and redox systems. In addition, phendione and its metal complexes have demonstrated relevant biological activities, including antibacterial, antifungal and antiprotozoal effects, attributed to DNA interaction, redox cycling, inhibition of key enzymes and interference with essential microbial processes such as protein synthesis. In the context of the escalating global burden of antimicrobial resistance, the discovery and development of innovative therapeutic strategies have become an urgent priority. In this scenario, phendione-based complexes have emerged as promising candidates owing to their remarkable structural diversity, versatile coordination chemistry, tunable physicochemical properties and ability to engage multiple and distinct mechanisms of action that differ from those of currently available clinical antimicrobial drugs. These characteristics provide opportunities for overcoming existing therapeutic limitations and expanding the arsenal of antimicrobial agents, particularly against clinically relevant pathogenic microorganisms, including multidrug- and pan-resistant strains for which effective treatment options remain critically limited. The present review provides a comprehensive and critical analysis of the current literature concerning the synthesis, structural features and antimicrobial properties of phendione-containing complexes, highlighting their potential as promising next-generation antimicrobial agents and exploring their mechanisms of action, biological relevance and future perspectives in the development of innovative therapies.

Introdução Diante da magnitude da pandemia da COVID-19, os profissionais de saúde mal puderam se apropriar das poucas informações sobre a doença e já precisaram se preparar para assumir a linha de fr