Abstract
Silver nanoparticles have received considerable interest as new “nanoantibiotics” with the potential to kill drug-resistant microorganisms. Recently, a class of new core-shell nanostructures, Pd@Ag nanosheets (Pd@Ag NSs), were created using deposition techniques and demonstrated excellent inhibitory effects on various bacteria in vitro. In this study, we evaluated the antifungal activity of Pd@Ag NSs against common invasive fungal pathogens. Among these organisms, Cryptococcus neoformans complex species was most susceptible to Pd@Ag NSs, which exhibited potent antifungal activity against various molecular types or sources of cryptococcal strains including fluconazole-resistant isolates. The anticryptococcal activity of Pd@Ag NSs was significantly greater than fluconazole and similar to that of amphotericin B (AmB). At relatively high concentrations, Pd@Ag NSs exhibited fungicidal activity against Cryptococcus spp., which can likely be attributed to the disruption of cell integrity, intracellular protein synthesis, and energy metabolism. Intriguingly, Pd@Ag NSs also exhibited strong synergistic anti-cryptococcal fungicidal effects at low concentrations in combination with AmB but exhibited much better safety in erythrocytes than AmB, even at the minimal fungicidal concentration. Therefore, Pd@Ag NSs may be a promising adjunctive agent for treating cryptococcosis, and further investigation for clinical applications is required.
Highlights
Cryptococcus neoformans complex species is one of the most important invasive fungal pathogens worldwide and can cause life-threatening meningoencephalitis in both immunocompromised and immunocompetent populations [1, 2]
By changing the sizes of the Pd nanosheets (Pd NSs), Pd@Ag nanosheets with sizes similar to those of the original Pd NSs seeds could be obtained
We evaluated the fungistatic activities of Pd@Ag NSs with different diameters (11–120 nm) against common invasive fungal pathogens using the standard microdilution method
Summary
Cryptococcus neoformans complex species (including C. neoformans and C. gattii) is one of the most important invasive fungal pathogens worldwide and can cause life-threatening meningoencephalitis in both immunocompromised and immunocompetent populations [1, 2]. The mortality rate remains at about 20% even with prompt treatment, while it is much higher (30%)in resource-limited areas such as sub-Saharan Africa [4,5,6,7]. This poor outcome is largely attributed to factors such as the limited number of available antifungal agents, their significant toxic effects, and the emergence of resistant fungal strains [8,9,10]. A recent global survey of approximately 3,000 cryptococcal isolates indicated a progressive increase of FLZ-resistance from 7.3% in 1997 to 11.7% in 2007 [16]. There is an urgent need to develop novel antimicrobial agents and/or new methods for effective anticryptococcal treatment
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