•Pollution alters the fungal community composition of river water.•Candida glabrata and Clavispora lusitaniae occurrence is linked with pollution.•Meyerozyma guilliermondii dominated culturable yeast ...populations in rainy seasons.•Fluconazole-resistant yeast strains were recovered from river water.•Risk of mycosis increased concurrently with pollution levels of river water.
River water is an essential human resource that may be contaminated with hazardous microorganisms. However, the risk of yeast infection through river water exposure is unclear because it is highly dependant on individual susceptibility and has therefore not been well-studied, to date. To evaluate this undefined risk, we analysed the fungal communities in less polluted (LP) and highly polluted (HP) river water, as determined using principal coordinate analysis of pollution indicators. We enumerated culturable yeasts using a thermally selective isolation procedure (37 °C) and thus promoted the growth of potentially opportunistic species. Yeast species identified as clinically relevant were then tested for antifungal resistance. In addition, we propose a quantitative microbial risk assessment (QMRA) framework to quantitatively assess the potential risk of yeast infection. Our results indicated that pollution levels significantly altered fungal communities (p = 0.007) and that genera representing opportunistic and pathogenic members were significantly more abundant in HP waters (p = 0.038). Additionally, the yeast species Candida glabrata and Clavispora lusitaniae positively correlated with other pollution indicators, demonstrating the species’ indicator potential. Our QMRA results further indicate that higher risk of infection is associated with increased water pollution levels (considering both physicochemical and bacterial indicators). Furthermore, yeast species with higher pathogenic potential present an increased risk of infection despite lower observed concentrations in the river water. Interestingly, the bloom of Meyerozyma guilliermondii during the wet season suggests that other environmental factors, such as dissolved oxygen levels and water turbulence, might affect growth characteristics of yeasts in river water, which consequently affects the distribution of annual infection risks. The presence of antifungal resistant yeasts, observed in this study, could further contribute to variation in risk distribution. Research on the ecophysiology of yeasts in these environments is therefore necessary to ameliorate the uncertainty and sensitivity of the proposed QMRA model. In addition to the vital knowledge on opportunistic and pathogenic yeast occurrence in river water and their observed association with pollution, this study provides valuable methods and insights to initiate future QMRAs of yeast infections.
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Background TA-8995 is a potent inhibitor of cholesteryl ester transfer protein (CETP) with beneficial effects on lipids and lipoproteins. The effect of TA-8995 on cholesterol efflux capacity (CEC), a ...measure of high-density lipoprotein (HDL) function, and HDL subparticle distribution is largely unknown. Objective To assess the effect of the CETP inhibitor TA-8995 on ABCA1- and non–ABCA1-driven CEC and on HDL particle distribution. Methods Total, non–ABCA1-, and ABCA1-specific CEC from J774 cells and HDL subclass distribution assessed by two-dimensional gel electrophoresis were measured at baseline and after 12-week treatment in 187 mild-dyslipidemic patients randomized to placebo, 1 mg, 5 mg, 10 mg TA-8995, or 10 mg TA-8995 combined with 10 mg rosuvastatin (NCT01970215). Results Compared with placebo, total, non–ABCA1-, and ABCA1-specific CEC were increased dose dependently by up to 38%, 72%, and 28%, respectively, in patients randomized to 10 mg of TA-8995. PreBeta-1 HDL, the primary acceptor for ABCA1-driven cholesterol efflux, was increased by 36%. This increase in preBeta-1 HDL correlated significantly with the total and the ABCA1-driven CEC increase, whereas the high-density lipoprotein cholesterol (HDL-C) increase did not. Conclusion TA-8995 dose dependently increased not only total and non–ABCA1-specific CEC but also ABCA1-specific CEC and preBeta-1 HDL particle levels. These findings suggest that TA-8995 not only increases HDL-C levels but also promotes functional properties of HDL particles. This CETP inhibitor–driven preBeta-1 HDL increase is an important predictor of both ABCA1 and total CEC increase, independent of HDL-C increase. Whether these changes in HDL particle composition and functionality have a beneficial effect on cardiovascular outcome requires formal testing in a cardiovascular outcome trial.
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