In vivo and in vitro activity of a bis-arylidenecyclo-alkanone against fluconazole-susceptible and -resistant isolates of Candida albicans.

OBJECTIVES: Candida albicans is a commensal organism and opportunistic pathogen associated both with superficial (mucosal and cutaneous) and systemic infections. Extensive use of antifungal agents has led to reduced susceptibility to the few existing drugs, which has encouraged the search for novel antifungal agents. Therefore, the present study investigated the antifungal activity of 2,6-bis[(E)-(4-pyridyl)methylidene]cyclohexanone (PMC) against C. albicans. METHODS: The in vitro activity of PMC was evaluated against C. albicans. Additionally, an invertebrate infection model in Caenorhabditis elegans as well as two infected murine models of oral and systemic candidiasis were used to determine the antifungal efficacy of PMC in vivo. RESULTS: Minimum inhibitory concentrations (MICs) of PMC ranged from 4-32µg/mL against nine clinical and two reference C. albicans isolates. Interestingly, PMC inhibited filamentation in vitro at subinhibitory concentrations similar to fluconazole. PMC also showed low toxicity against murine macrophages and human erythrocytes. In the invertebrate infection model, PMC was efficient in prolonging survival of C. elegans infected with C. albicans SC5314. Treatment with PMC was efficient both in murine models of systemic and oral candidiasis and was similar to that observed with conventional drug treatments (nystatin and fluconazole). CONCLUSIONS: The results of this study indicate the therapeutic potential of PMC as it was able to inhibit filamentation of C. albicans in vitro. These alterations to the fungi by PMC resulted in a reduction of oral and systemic infection in mice. In conclusion, we present promising evidence of the anticandidal activity of PMC in vitro and in vivo.

Systemic infection by Spencermartinsiella sp. in a Nile crocodile (Crocodylus niloticus) / Infecção sistêmica por Spencermartinsiella sp. em um crocodilo do Nilo (Crocodylus niloticus)

A male adult crocodile (Crocodylus niloticus) was diagnosed with systemic yeast infection. Histologically, there were extensive areas of necrosis in the lung, which were associated with a diffuse severe lympho-plasmo-histiocytic inflammatory infiltrate, with numerous multinucleated giant cells, and myriads of intralesional pseudo-hyphae and yeast like organisms within distended foveolae. Necrotic foci were also observed in the mucosa of the digestive tract, trachea, tunica intima of arteries, liver, and heart, with a marked inflammatory lympho-histiocytic infiltrate, with large numbers of epithelioid macrophages and giant cells, and intralesional and intravascular pseudo-hyphae and yeast-like organisms. Oval yeast structures with 4 to 6 µm in diameter and 5 to 8 µm thick paralleled-wall pseudo-hyphae were observed in PAS or GMS stained sections. PCR with DNA template extracted from paraffin embedded tissues amplified the D1/D2 domains of the large subunit rRNA gene, which was sequenced and found to be identical to sequences of a new species, isolated from rotting wood in Brazil, of the genus Spencermartinsiella, which its closest relative is Spencermartinsiella cellulosicola.(AU)

Um crocodilo macho adulto (Crocodylus niloticus) foi diagnosticado com infecção fúngica sustêmica. Histologicamente, havia extensas áreas de necrose no pulmão, que estavam associadas com infiltrado inflamatório linfo-plasmo-histiocitário, com numerosas células gigantes multinucleadas e miríade de pseudo-hifas e organismos leveduriformes intralesionais, dentro de favéolas distendidas. Focos necróticos também foram observados na mucosa do trato digestório, traquéia, túnica íntima de artérias, fígado e coração, com acentuado infiltrado inflamatório linfo-histiocitário, com grande número de macrófagos epitelioides e células gigantes e hifas e organismos leveduriformes intralesionais e intravasculares. Cortes corados por PAS e GMS evidenciaram estruturas leveduriformes ovais com 4 a 6 µm de diâmetro e pseudo-hifas de paredes espessas e paralelas com 5 a 8 µm. PCR realizado com DNA extraído de material parafinizado amplificou os domínios D1/D2 da subunidade maior do gene rRNA, cuja sequencia foi idêntica a sequências de uma nova espécie, isolada no Brasil de madeira em decomposição, do gênero Spencermartinsiella, cuja espécie mais próxima é Spencermartinsiella cellulosicola.(AU)