Multifunctional Gold Nanozyme-Engineered Amphotericin B for Enhanced Antifungal Infection Therapy.

Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (Vmax ) 3.4 times higher than that of AuNPs for the catalytic reaction of H2 O2 . Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases.

Therapeutic effect of iturin A on Candida albicans oral infection and its pathogenic factors.

Candida albicans is responsible for conditions ranging from superficial infections such as oral or vaginal candidiasis to potentially fatal systemic infections. It produces pathogenic factors contributing to its virulence. Iturin A, a lipopeptide derived from Bacillus sp., exhibits a significant inhibitory effect against C. albicans. However, its exact mechanism in mitigating the pathogenic factors of C. albicans remains to be elucidated. This study aimed to explore the influence of iturin A on several pathogenic attributes of C. albicans, including hypha formation, cell membrane permeability, cell adhesion, biofilm formation, and therapeutic efficacy in an oral C. albicans infection model in mice. The minimal inhibitory concentration of iturin A against C. albicans was determined to be 25 µg/mL in both YEPD and RPMI-1640 media. Iturin A effectively inhibited C. albicans hyphal formation, decreased cell viability within biofilms, enhanced cell membrane permeability, and disrupted cell adhesion in vitro. Nonetheless, iturin A did not significantly affect the phospholipase activity or hydrophobicity of C. albicans. A comparative study with nystatin demonstrated the superior therapeutic efficacy of iturin A in a mouse model of oral C. albicans infection, significantly decreasing C. albicans count and inhibiting both fungal hypha formation and tongue surface adhesion. High-dose iturin A treatment (25 µg/mL) in mice had no significant effects on blood indices, tongue condition, or body weight, indicating the potential for iturin A in managing oral infections. This study confirmed the therapeutic potential of iturin A and provided valuable insights for developing effective antifungal therapies targeting C. albicans pathogenic factors.

Simulated Microgravity Accelerates Alloy Corrosion by Aspergillus sp. via the Enhanced Production of Organic Acids.

Metal corrosion caused by Aspergillus sp. was shown to be significantly enhanced on a space station, but its mechanism is still unknown. To simulate this on earth, the corrosion capability of A. carbonarius on five metal sheets was investigated under simulated microgravity. Also, the effect of metal ions on growth and organic acid production was determined. Results showed that A. carbonarius could corrode all five types of metal, including Ti alloy, aluminum alloy, iron, and aluminum and copper sheet, and the corrosion was intensified under simulated microgravity. Energy dispersive X-ray spectrometry (EDS) analysis showed that metal ions enriched on A. carbonarius spores, especially iron, aluminum ions, and copper ions, indicating that A. carbonarius can use these metal ions. In particular, the content of oxalic acid was significantly increased after A. carbonarius cocultured with five metal materials under simulated microgravity. Al3+, Fe3+, and Cu2+ at the concentration of 0.3 mg/mL and Mg2+ at 0.8 mg/mL significantly promoted the growth and oxalic acid and citric acid production of A. carbonarius and A. niger under normal gravity and simulated microgravity. Comparing the impact of metal ions and metal sheets on the production of organic acids, it can be inferred that oxalic acid may dominate in the corrosion process of A. carbonarius. In summary, molds promoted metal corrosion by producing organic acids, and the released metal ions will further promote the growth of mold and the accumulation of organic acids. This may be an important reason for the intensification of mold corrosion under microgravity. IMPORTANCE The space station and other long-term manned spacecrafts will experience the risk of microbial corrosion, especially mold, which will be harmful to the platform system and astronauts. Aspergillus sp. has been widely reported to produce organic acids that corrode and destroy materials, and the ability of these crafts to fly through space can be significantly affected. Research on the mechanism that causes enhanced corrosion ability of fungi in space stations is important to control their growth. Our research focuses on the interaction between mold and metals. In particular, it is found that metal ions promote mold growth and produce organic acids, thus accelerating mold corrosion of metals. Our results provide a new perspective for the control of fungal corrosion under simulated microgravity.