Capric Acid Secreted by S. boulardii Inhibits C. albicans Filamentous Growth, Adhesion and Biofilm Formation

Candidiasis are life-threatening systemic fungal diseases, especially of gastro intestinal track, skin and mucous membranes lining various body cavities like the nostrils, the mouth, the lips, the eyelids, the ears or the genital area. Due to increasing resistance of candidiasis to existing drugs, it is very important to look for new strategies helping the treatment of such fungal diseases. One promising strategy is the use of the probiotic microorganisms, which when administered in adequate amounts confer a health benefit. Such a probiotic microorganism is yeast Saccharomyces boulardii, a close relative of baker yeast. Saccharomyces boulardii cells and their extract affect the virulence factors of the important human fungal pathogen C. albicans, its hyphae formation, adhesion and biofilm development. Extract prepared from S. boulardii culture filtrate was fractionated and GC-MS analysis showed that the active fraction contained, apart from 2-phenylethanol, caproic, caprylic and capric acid whose presence was confirmed by ESI-MS analysis. Biological activity was tested on C. albicans using extract and pure identified compounds. Our study demonstrated that this probiotic yeast secretes into the medium active compounds reducing candidal virulence factors. The chief compound inhibiting filamentous C. albicans growth comparably to S. boulardii extract was capric acid, which is thus responsible for inhibition of hyphae formation. It also reduced candidal adhesion and biofilm formation, though three times less than the extract, which thus contains other factors suppressing C. albicans adherence. The expression profile of selected genes associated with C. albicans virulence by real-time PCR showed a reduced expression of HWP1, INO1 and CSH1 genes in C. albicans cells treated with capric acid and S. boulardii extract. Hence capric acid secreted by S. boulardii is responsible for inhibition of C. albicans filamentation and partially also adhesion and biofilm formation

Additive Contributions of Two Manganese-Cored Superoxide Dismutases (MnSODs) to Antioxidation, UV Tolerance and Virulence of Beauveria bassiana

The biocontrol potential of entomopathogenic fungi against arthropod pests depends on not only their virulence to target pests but tolerance to outdoor high temperature and solar UV irradiation. Two Beauveria bassiana superoxide dismutases (SODs), BbSod2 and BbSod3, were characterized as cytosolic and mitochondrial manganese-cored isoenzymes (MnSODs) dominating the total SOD activity of the fungal entomopathogen under normal growth conditions. To probe their effects on the biocontrol potential of B. bassiana, ΔBbSod2, ΔBbSod3, and three hairpin RNA-interfered (RNAi) mutants with the transcripts of both BbSod2 and BbSod3 being suppressed by 91–97% were constructed and assayed for various phenotypic parameters in conjunction with ΔBbSod2/BbSod2, ΔBbSod3/BbSod3 and wild-type (control strains). In normal cultures, the knockout and RNAi mutants showed significant phenotypic alterations, including delayed sporulation, reduced conidial yields, and impaired conidial quality, but little change in colony morphology. Their mycelia or conidia became much more sensitive to menadione or H2O2-induced oxidative stress but had little change in sensitivity to the hyperosmolarity of NaCl and the high temperature of 45°C. Accompanied with the decreased antioxidative capability, conidial tolerances to UV-A and UV-B irradiations were reduced by 16.8% and 45.4% for ΔBbSod2, 18.7% and 44.7% for ΔBbSod3, and ∼33.7% and ∼63.8% for the RNAi mutants, respectively. Their median lethal times (LT50s) against Myzus persicae apterae, which were topically inoculated under a standardized spray, were delayed by 18.8%, 14.5% and 37.1%, respectively. Remarkably, the effects of cytosolic BbSod2 and mitochondrial BbSod3 on the phenotypic parameters important for the fungal bioncontrol potential were additive, well in accordance with the decreased SOD activities and the increased superoxide levels in the knockout and RNAi mutants. Our findings highlight for the first time that the two MnSODs co-contribute to the biocontrol potential of B. bassiana by mediating cellular antioxidative response

Abstract P144: Covid-19 And The Use Of Angiotensin-converting Enzyme Inhibitors And Receptor Blockers. Real World Experience

Background: Concerns exist that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) increase susceptibility to coronavirus SARS CoV-2 (the virus that causes the disease COVID-19) and the likelihood of severe COVID-19 illness. Methods: This is a single-center retrospective cohort study of 172 patients diagnosed with 2019 Novel Coronavirus (SARS-CoV-2) between March of 2020 and May of 2020. Our study aimed to investigate the impact of ACEI and/or ARBs on the in-hospital mortality, intensive care unit (ICU) admission, hospital length of stay (LOS), and ICU LOS of patients with COVID-19. Results: This cohort of 172 patients included 88 (51%) women with a mean age of 58±17 years. Patients who had a history of using ACEI/ARBs were older 68±14 vs. 54±17 (P<0.0001). They were more likely to be obese 28(65%) vs. 52(40%) p=0.0054, have hypertension 44(100%) vs 42(33%) p<0.0001, diabetes mellitus 18(40%) vs 13 (10%) p<0.0001, and chronic kidney disease 5(11%) vs. 1(0.8%) p= 0.0011 than patients not using ACEI/ARBs. On the other hand, the prevalence of coronary artery disease (p=0.3791), and chronic heart failure (p=0.8037) was similar between the two groups. Outcomes: There was significantly higher in-hospital mortality in patients who used ACEI/ARBs than non-users (33% vs. 13%, p=0.0039, respectively). To evaluate the effect of ACEI/ARBs on mortality after controlling for confounding factors, multivariable logistic regression (MLR) was performed based on age (p=0.0003), obesity (p=0.3394), hypertension (p=0.4159), diabetes mellitus (p=0.0144), and chronic kidney disease (0.3189). The MLR showed no significant differences in mortality between patients who used ACEI/ARBs and non-users (p= 0.8372). Admission to ICU was more likely in patients who used ACEI/ARBs than non-users (28% vs. 13%, p=0.0384 respectively), while hospital LOS (6±9 vs. 4±6, p=0.1240 respectively), and ICU LOS (12±12 vs. 8±5, p= 0.3253 respectively) were similar between the two groups. Conclusion: This study suggests that the use of ACEI/ARBs associated with higher mortality in patients with COVID-19. This is likely attributed to the fact that patients who use these medications are older and are more likely to have diabetes mellitus and hypertension