Bionized Nanoferrite Particles Alter the Course of Experimental Cryptococcus neoformans Pneumonia.

Cryptococcosis is a devastating fungal disease associated with high morbidity and mortality even when treated with antifungal drugs. Bionized nanoferrite (BNF) nanoparticles are powerful immunomodulators, but their efficacy for infectious diseases has not been investigated. Administration of BNF nanoparticles to mice with experimental cryptococcal pneumonia altered the outcome of infection in a dose response manner as measured by CFU and survival. The protective effects were higher at lower doses, with reductions in IL-2, IL-4, and TNF-α, consistent with immune modulation whereby reductions in inflammation translate into reduced host damage, clearance of infection, and longer survival.

Amoeba Predation of Cryptococcus neoformans Results in Pleiotropic Changes to Traits Associated with Virulence.

Amoeboid predators, such as amoebae, are proposed to select for survival traits in soil microbes such as Cryptococcus neoformans; these traits can also function in animal virulence by defeating phagocytic immune cells, such as macrophages. Consistent with this notion, incubation of various fungal species with amoebae enhanced their virulence, but the mechanisms involved are unknown. In this study, we exposed three strains of C. neoformans (1 clinical and 2 environmental) to predation by Acanthamoeba castellanii for prolonged times and then analyzed surviving colonies phenotypically and genetically. Surviving colonies comprised cells that expressed either pseudohyphal or yeast phenotypes, which demonstrated variable expression of traits associated with virulence, such as capsule size, urease production, and melanization. Phenotypic changes were associated with aneuploidy and DNA sequence mutations in some amoeba-passaged isolates, but not in others. Mutations in the gene encoding the oligopeptide transporter (CNAG_03013; OPT1) were observed among amoeba-passaged isolates from each of the three strains. Isolates derived from environmental strains gained the capacity for enhanced macrophage toxicity after amoeba selection and carried mutations on the CNAG_00570 gene encoding Pkr1 (AMP-dependent protein kinase regulator) but manifested reduced virulence in mice because they elicited more effective fungal-clearing immune responses. Our results indicate that C. neoformans survival under constant amoeba predation involves the generation of strains expressing pleiotropic phenotypic and genetic changes. Given the myriad potential predators in soils, the diversity observed among amoeba-selected strains suggests a bet-hedging strategy whereby variant diversity increases the likelihood that some will survive predation.IMPORTANCECryptococcus neoformans is a ubiquitous environmental fungus that is also a leading cause of fatal fungal infection in humans, especially among immunocompromised patients. A major question in the field is how an environmental yeast such as C. neoformans becomes a human pathogen when it has no need for an animal host in its life cycle. Previous studies showed that C. neoformans increases its pathogenicity after interacting with its environmental predator amoebae. Amoebae, like macrophages, are phagocytic cells that are considered an environmental training ground for pathogens to resist macrophages, but the mechanism by which C. neoformans changes its virulence through interactions with protozoa is unknown. Our study indicates that fungal survival in the face of amoeba predation is associated with the emergence of pleiotropic phenotypic and genomic changes that increase the chance of fungal survival, with this diversity suggesting a bet-hedging strategy to ensure that some forms survive.

Coincidence of biophoton emission by wheat seedlings during simultaneous, transcontinental germination tests.

Measurements of spontaneous ultra-weak light (biophoton) emission from native Brazilian and German wheat seedlings in three simultaneous series of germination tests are presented, two run in Germany and one in Brazil. Seedlings in both countries presented semi-circadian rhythms of emission that were in accordance with the local lunisolar gravimetric tidal acceleration, as did seeds which had been transported from Brazil to Germany. The simultaneity of the photon emission patterns in all tests argues for the lunisolar tide and its rhythmic variations as regulators of the natural rhythm of photon emission. However, seedlings from seed samples transported from Brazil to Germany showed, in addition, a temporary disturbance within the emission periodicity which may indicate a possible short-term acclimatization to the new location.