Heavy Rainfall Impacts on Trihalomethane Formation in Contrasting Northwestern European Potable Waters.

There is emerging concern over the impact of extreme events such as heavy rainfall on the quality of water entering the drinking water supply from aboveground sources, as such events are expected to increase in magnitude and frequency in response to climate change. We compared the impact of rainfall events on streamwater quality in four contrasting upland (peatland and mineral soil) and lowland agricultural catchments used to supply drinking water in France (Brittany) and the United Kingdom (North Wales) by analyzing water samples collected before, during, and after specific events. At all four streams, heavy rainfall led to a considerable rise in organic matter concentration ranging from 48 to 158%. Dissolved organic carbon (DOC) quality, as determined using specific ultraviolet absorbance, changed consistently at all sites during rainfall events, with a greater proportion of aromatic and higher molecular weight compounds following the onset of rainfall. However, the change in DOC quality and quantity did not significantly alter the trihalomethane formation potential. We observed small increases in trihalomethane (THM) generation only at the Welsh peatland and agricultural sites and a small decrease at the Brittany agricultural site. The proportion of brominated THMs in chlorinated waters was positively correlated with bromide/DOC ratio in raw waters for all sites and hydrological conditions. These results provide a first indication of the potential implications for surface-based drinking water resources resulting from expected future increases in rainfall event intensity and extension of dry periods with climate changes.

Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa.

Malassezia globosa cytochromes P450 CYP51 and CYP5218 are sterol 14α-demethylase (the target of azole antifungals) and a putative fatty acid metabolism protein (and a potential azole drug target), respectively. Lanosterol, eburicol and obtusifoliol bound to CYP51 with Kd values of 32, 23 and 28 µM, respectively, catalyzing sterol 14α-demethylation with respective turnover numbers of 1.7 min(-1), 5.6 min(-1) and 3.4 min(-1). CYP5218 bound a range of fatty acids with linoleic acid binding strongest (Kd 36 µM), although no metabolism could be detected in reconstitution assays or role in growth on lipids. Clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole and ketaminazole bound tightly to CYP51 (Kd ≤ 2 to 11 nM). In contrast, fluconazole did not bind to CYP5218, voriconazole and ketaminazole bound weakly (Kd ~107 and ~12 µM), whereas ketoconazole, clotrimazole and itraconazole bound strongest to CYP5218 (Kd ~1.6, 0.5 and 0.4 µM) indicating CYP5218 to be only a secondary target of azole antifungals. IC50 determinations confirmed M. globosa CYP51 was strongly inhibited by azole antifungals (0.15 to 0.35 µM). MIC100 studies showed itraconazole should be considered as an alternative to ketoconazole given the potency and safety profiles and the CYP51 assay system can be used in structure-activity studies in drug development.