Browsing by Author "Sass, Gabriele"
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- Diphenyl diselenide and its interaction with antifungals against Aspergillus sppPublication . Melo, Aryse Martins; Poester, Vanice Rodrigues; Trapaga, Mariana; Nogueira, Cristina Wayne; Zeni, Gilson; Martinez, Marife; Sass, Gabriele; Stevens, David A; Xavier, Melissa OrzechowskiGiven the few antifungal classes available to treat aspergillosis, this study aimed to evaluate the in vitro antifungal activity of diphenyl diselenide (PhSe)2 alone and in combination with classical antifungals against Aspergillus spp., and its in vivo activity in a systemic experimental aspergillosis model. We performed in vitro broth microdilution assay of (PhSe)2 against 32 Aspergillus isolates; and a checkboard assay to test the interaction of this compound with itraconazole (ITC), voriconazole (VRC), amphotericin B (AMB), and caspofungin (CAS), against nine Aspergillus isolates. An experimental model of invasive aspergillosis in mice was studied, and survival curves were compared between an untreated group and groups treated with 100 mg/kg ITC, or (PhSe)2 in different dosages (10 mg/kg, 50 mg/kg and 100 mg/kg). All Aspergillus non-fumigatus and 50% of A. fumigatus were inhibited by (PhSe)2 in concentrations ≤ 64 µg/ml, with significant differences in MICs between the sections. Synergism or additive effect in the in vitro (PhSe)2 interaction with VRC and CAS was observed against the majority of isolates, and with ITC against the non-fumigatus strains. In addition to the inhibitory interaction, (PhSe)2 was able to add a fungicidal effect to CAS. Survival curves from the systemic experimental aspergillosis model demonstrated that the inoculum caused an acute and lethal infection in mice, and no treatment applied significantly prolonged survival over that of the control group. The results highlight the promising activity of (PhSe)2 against Aspergillus species, but more in vivo studies are needed to determine its potential applicability in aspergillosis treatment.
- Synergy Between Pseudomonas aeruginosa Filtrates And Voriconazole Against Aspergillus fumigatus Biofilm Is Less for Mucoid Isolates From Persons With Cystic FibrosisPublication . Sass, Gabriele; Marsh, Julianne J.; Shrestha, Pallabi; Sabino, Raquel; Stevens, David A.Persons with cystic fibrosis (CF) frequently suffer from Pseudomonas aeruginosa and Aspergillus fumigatus co-infections. There is evidence that co-infections with these interacting pathogens cause airway inflammation and aggravate deterioration of lung function. We recently showed that P. aeruginosa laboratory isolates synergistically interact with the anti-fungal azole voriconazole (VCZ), inhibiting biofilm metabolism of several A. fumigatus laboratory strains. Interaction was usually mediated via pyoverdine, but also via pyocyanin or pyochelin. Here we used planktonic filtrates of 7 mucoid and 9 non-mucoid P. aeruginosa isolates from CF patients, as well as 8 isolates without CF origin, and found that all of these isolates interacted with VCZ synergistically at their IC50 as well as higher dilutions. CF mucoid isolates showed the weakest interactive effects. Four non-mucoid P. aeruginosa CF isolates produced no or very low levels of pyoverdine and did not reach an IC50 against forming A. fumigatus biofilm; interaction with VCZ still was synergistic. A VCZ-resistant A. fumigatus strain showed the same level of susceptibility for P. aeruginosa anti-fungal activity as a VCZ-susceptible reference strain. Filtrates of most Pseudomonas isolates were able to increase anti-fungal activity of VCZ on a susceptible A. fumigatus strain. This was also possible for the VCZ-resistant strain. In summary these data show that clinical P. aeruginosa isolates, at varying degrees, synergistically interact with VCZ, and that pyoverdine is not the only molecule responsible. These data also strengthen the idea that during co-infections of A. fumigatus and P. aeruginosa lower concentrations of VCZ might be sufficient to control fungal growth.