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[Ag 2 (imH) 4 ](salH) 2 , in comparison to the prescription drug silver sulfadiazine, had significantly better anti-bacterial qualities, whilst against the fungus C. albicans it was 47 times more potent than the marketed drug ketoconazole.

Caspofungin is a member of the echinocandin group of antifungals and inhibits the activity of beta-glucan synthase thus disrupting cell wall formation and function. While the potent antifungal activity of this agent is well established, this paper analyzed the response of Candida albicans to caspofungin. Exposure of yeast cells to 0.19 microg/ml caspofungin for 1 to 4 h induced nuclear translocation of Cap1p which was confirmed by Western blotting and confocal microscopy. Caspofungin-treated cells demonstrated increased expression of a number of genes associated with the oxidative stress response, including glutathione reductase (GLR1), mitochondrial processing protease (MAS1) and manganese-superoxide dismutase (SOD2) as well as elevated activity of glutathione reductase and superoxide dismutase. Caspofungin treatment also leads to the nuclear localization of Hog1p as visualized by Western blot using anti-phospho-p38 MAPK (Thr180/Tyr182) antibody. This translocation event lead to increased mRNA levels of catalase (CAT1) but not alkyl hydroperoxide reductase (AHP1). The activity of catalase was increased and reached a maximum at 2 h. In addition, pre-exposure of C. albicans to hydrogen peroxide (0.5 mM, 60 min) conferred an increased tolerance to caspofungin. The data presented here highlight the potent antifungal activity of caspofungin and demonstrate that upon exposure to this agent, C. albicans activates the Cap and Hog pathways in an attempt to limit the oxidative and osmotic stresses associated with this drug.

The Ag(I) ion has well established antibacterial and antifungal properties. Exposure of Staphylococcus aureus to MIC 80 AgNO 3 (3 lg/ml) lead to an increase in the activity of superoxide dismutase, glutathione reductase and catalase at 30 min but activity declined by 60 min. In addition, exposure of cells to this metal ion for 1 h lead to increased expression of a number of proteins such as elongation factors Ts, Tu and G, fructose-bisphosphate aldolase and triosephosphate isomerase but their expression declined following 4 h exposure. ATP binding cassette transporter protein and oligoendopeptidase F showed increased expression at 4 h. While Ag(I) is a potent antimicrobial agent this work demonstrates that S. aureus can mount a short-term protective response to exposure to the metal ion but that this is eventually overcome.