Pathogenic potential of an environmental Aspergillus fumigatus strain recovered from soil of Pygoscelis papua (Gentoo penguins) colony in Antarctica.

Aspergillus fumigatus is a common opportunistic pathogen in different animals, including birds such as penguins. For the first time, a fungal strain identified as A. fumigatus was isolated from soil in the nests of gentoo penguins, Pygoscelis papua, on Livingston Island, South Shetland Islands (maritime Antarctica). This isolate (A. fumigatus UFMGCB 11829) displayed a series of potentially pathogenic characteristics in vitro. We evaluated its detailed molecular taxonomy and submitted the A. fumigatus UFMGCB 11829 Antarctic strain to in vivo pathogenic modelling. The isolate was confirmed to represent A. fumigatus morphological and phylogenetic analysis showed that it was closely related to A. fumigatus sequences reported from animals, immunosuppressed humans, storage grains, plants and soils. The strain displayed the best mycelial growth and conidia production at 37 ºC; however, it was also able to grow and produce conidia at 15º, demonstrating its capability to survive and colonize penguin nest at least in the summer season in maritime Antarctica. In pathogenicity tests, healthy mice did not showed symptoms of infection; however, 50% lethality was observed in immunosuppressed mice that were inoculated with 106 and 107 spores. Lethality increased to 100% when inoculated with 108 spores. Our data highlight the potential pathogenicity of opportunistic A. fumigatus that may be present in the Antarctic, and the risks of both their further transfer within Antarctica and outwards to other continents, risks which may be exacerbated due global climatic changes.

Does maritime Antarctic permafrost harbor environmental fungi with pathogenic potential?

We assessed the potentially pathogenic fungi present in Antarctic permafrost and the overlying active layer on King George, Robert, Livingston and Deception Islands in the South Shetland Islands archipelago, maritime Antarctica. Permafrost and active layer sub-samples were incubated at 37 °C to select fungi able to grow inside the human body. A total of 67 fungal isolates were obtained, 27 from the permafrost and 40 from the active layer. These represented 18 taxa of the genera Alternaria, Aspergillus, Curvularia, Penicillium, Rhodotorula and Talaromyces. The majority of fungi detected occurred exclusively either in the permafrost or the active layer at each site. Only Aspergillus thermomutatus, Penicillium cf. chrysogenum and Rhodotorula cf. mucilaginosa were present in both permafrost and active layer samples from the same site. The yeast R. cf. mucilaginosa was recovered from both in at least two sites. The genus Penicillium was the most abundant and widely distributed genus in both permafrost and active layer samples across the sites sampled. All fungal isolates were screened using enzymatic, pH and antifungal assays to identify their virulence potential. Aspergillus hiratsukae, A. thermomutatus and R. cf. mucilaginosa, known human opportunistic fungi, were identified, displayed phospholipase, esterase, proteinase and hemolytic activities. All three also displayed the ability to grow at 40°, 45° and/or 50 °C and resistance to fluconazole and itraconazole; additionally, R. cf. mucilaginosa showed resistance to amphotericin B and viability after 100 d at -80 °C. A. thermomutatus UFMGCB 17415 killed the entire larvae of Tenebrio molitor in six days and R. cf. mucilaginosa UFMGCB 17448 and 17473 in three and four days, respectively. The melting of maritime Antarctic permafrost as a result of climate change may threaten the release of wild strains of pathogenic fungi geographically isolated for long time, which may in turn be transported within and beyond Antarctica by different biological and non-biological vectors.

Randomized, phase 1/2, double-blind pioglitazone repositioning trial combined with antifungals for the treatment of cryptococcal meningitis - PIO study.

BACKGROUND: Cryptococcosis affects more than 220,000 patients/year, with high mortality even when the standard treatment [amphotericin B (AMB), 5-flucytosin (5-FC) and fluconazole] is used. AMB presents high toxicity and 5-FC is not currently available in Brazil. In a pre-clinical study, pioglitazone (PIO - an antidiabetic drug) decreased AMB toxicity and lead to an increased mice survival, reduced morbidity and fungal burden in brain and lungs. The aim of this trial is to evaluate the efficacy and safety of PIO combined with standard antifungal treatment for human cryptococcosis. METHODS: A phase 1/2, randomized, double blind, placebo-controlled trial will be performed with patients from Belo Horizonte, Brazil. They will be divided into three groups (placebo, PIO 15 mg/day or PIO 45 mg/day) and will receive an additional pill during the induction phase of cryptococcosis' treatment. Our hypothesis is that treated patients will have increased survival, so the primary outcome will be the mortality rate. Patients will be monitored for survival, side effects, fungal burden and inflammatory mediators in blood and cerebrospinal fluid. The follow up will occur for up 60 days. CONCLUSIONS: We expect that PIO will be an adequate adjuvant to the standard cryptococcosis' treatment. TRIAL REGISTRATION: ICTRP/WHO (and International Clinical Trial Registry Plataform (ICTRP/WHO) (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=RBR-9fv3f4), RBR-9fv3f4 (http://www.ensaiosclinicos.gov.br/rg/RBR-9fv3f4). UTN Number: U1111-1226-1535. Ethical approvement number: CAAE 17377019.0.0000.5149.