The rising burden of fungal infections presents a significant challenge to global healthcare, particularly with increasing antifungal resistance limiting treatment efficacy. Early detection and timely intervention remain critical, yet fungal pathogens employ diverse mechanisms to evade host immunity and develop resistance, undermining existing therapeutic options. Limited antifungal options and rising resistance necessitate novel treatment strategies. This review provides a comprehensive overview of conventional antifungal agents, their mechanisms of action, and emerging resistance pathways. Furthermore, it highlights recently approved and investigational antifungal compounds while evaluating innovative approaches such as nanotechnology, drug repurposing, and immunotherapy. Addressing antifungal resistance requires a multifaceted strategy that integrates novel therapeutics, enhanced diagnostic tools, and future research efforts to develop sustainable and effective treatment solutions.

• Keywords
• MDR, antifungal resistance, future strategies, nanotechnology,
• Publication type
• Journal Article MeSH
• Review MeSH

A virus-free (VF) A. fumigatus isolate has been shown to be resistant in competition with Pseudomonas as compared to the isogenic line infected with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1), and this phenotype was apparently related to alterations in iron metabolism. Here we investigated further the mechanisms underpinning this phenotype. The extracellular siderophore profiles of five isogenic VF and virus-infected (VI) strains were sampled at 24, 31, 48, 54, and 72 h in submerged cultures and quantitatively examined by liquid chromatography and mass spectrometry. Intracellular profiles of conidia and cultures at the stationary growth phase were defined. VF A. fumigatus demonstrated the best fitness represented by the fastest onset of its exponential growth when grown on an iron-limited mineral medium. The exponential phase and transitional production phase of the extracellular triacetylfusarinine C (TafC) were achieved at 24 and 31 h, respectively, contrary to VI strains, which acted more slowly. As a result, the TafC reservoir was consumed sooner in the VF strain. Additionally, the VF strain had lower ferricrocin and higher hydroxyferricrocin content in the pellet during the stationary phase. All of these differences were significant (Kruskal-Wallis, p < 0.01). In our study, the siderophore reservoir of a VF strain was consumed sooner, improving the fitness of the VF strain in competition with P. aeruginosa.

• Keywords
• Aspergillus fumigatus, Pseudomonas aeruginosa, intermicrobial competition, polymycovirus, siderophore,
• Publication type
• Journal Article MeSH

Rhizopus spp. are the most common etiological agents of mucormycosis, causing over 90% mortality in disseminated infections. The diagnosis relies on histopathology, culture, and/or polymerase chain reaction. For the first time, the glycosylation of rhizoferrin (RHF) was described in a Rhizopus microsporus clinical isolate by liquid chromatography and accurate tandem mass spectrometry. The fermentation broth lyophilizate contained 345.3 ± 13.5, 1.2 ± 0.03, and 0.03 ± 0.002 mg/g of RHF, imido-RHF, and bis-imido-RHF, respectively. Despite a considerable RHF secretion rate, we did not obtain conclusive RHF detection from a patient with disseminated mucormycosis caused by the same R. microsporus strain. We hypothesize that parallel antimycotic therapy, RHF biotransformation, and metabolism compromised the analysis. On the other hand, the full profile of posaconazole metabolites was retrieved by our in house software CycloBranch.

• Keywords
• Rhizopus microsporus, glycoside, human isolate, liquid chromatography, mass spectrometry, metabolite, posaconazole metabolism, rhizoferrin, siderophore,
• Publication type
• Journal Article MeSH