Melanins are ubiquitous complex polymers that are commonly known in humans to cause pigmentation of our skin. Melanins are also present in bacteria, fungi, and helminths. In this review, we will describe the diverse interactions of fungal melanin with the mammalian immune system. We will particularly focus on Cryptococcus neoformans and also discuss other major melanotic pathogenic fungi. Melanin interacts with the immune system through diverse pathways, reducing the effectiveness of phagocytic cells, binding effector molecules and antifungals, and modifying complement and antibody responses.

Imaging of infections has the potential to improve clinical outcomes, but pathogen-specific imaging strategies are currently unavailable. Given their target specificity, antimicrobials may be useful as molecular imaging ligands to target infections. Despite substantial development efforts, no antimicrobial-based ligands are approved for clinical use. This scoping review comprehensively surveys radiolabeled antimicrobials across antibacterial, antimycobacterial, antiviral, and antifungal drug classes, examining their progression through the translational pipeline. The review utilized PubMed and Google Scholar databases (1970–2025), following PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. Two reviewers independently screened titles, abstracts, and full-text articles; data were extracted, and content duplicates were removed. In total, 143 preclinical and 25 clinical articles met the selection criteria. In clinical studies, most tracers showed suboptimal specificity for infections, while some proved useful for pharmacokinetic characterization. Among preclinical studies, radiolabeled plazomicin and echinocandins (caspofungin and anidulafungin) exhibited the greatest number of preferred characteristics. In conclusion, ideal antimicrobial pharmacologic properties can be counterproductive for imaging, where rapid background clearance and a high target-to-non-target ratio (T/NT) are essential. Many radioligands demonstrate good tissue penetration but suboptimal washout, limiting their diagnostic value. In vivo pharmacokinetic applications during active infections are promising, though significant challenges remain for infection imaging.

Invasive fungal infections pose significant clinical challenges, owing to limited antifungal efficacy and poor tissue drug penetration. This study investigated whether low-intensity pulsed ultrasound (LIPUS) could enhance the antifungal activity of sub-minimal inhibitory concentrations (sub-MICs) of amphotericin B (AmB) and micafungin (MFG) against two strains from two phylogenetically distinct Candida species: Candida albicans and Candida glabrata. Growth inhibition was assessed following LIPUS (15 min, 50% duty cycle, 1 W/cm²) alone or in combination with sub-MIC antifungals. Time-kill assays and adenylate kinase (AK) release evaluated the cell viability and membrane integrity, respectively. LIPUS transiently but markedly delayed C. albicans growth and enhanced the antifungal effects of both AmB and MFG at sub-MIC levels. The combination of LIPUS and ¼ MIC AmB reduced CFU counts by over 3 log at 12 h and induced higher AK release compared to controls, indicating membrane leakage. In contrast, Candida glabrata showed minimal susceptibility to LIPUS, with low AK release and mitigation of the fungistatic effects of sub-MIC MFG. Our study demonstrates that LIPUS can potentiate sub-MIC antifungals against C. albicans but may have the opposite effect in C. glabrata. This strain-specific variation in response to LIPUS underscores the need for further investigation before LIPUS can be considered as a treatment-enhancement strategy.