Full-genomic Network Inference for Non-model organisms: A Case Study for the Fungal Pathogen Candida albicans

Reverse engineering of full-genomic interaction networks based on compendia of expression data has been successfully applied for a number of model organisms. This study adapts these approaches for an important non-model organism: The major human fungal pathogen Candida albicans. During the infection process, the pathogen can adapt to a wide range of environmental niches and reversibly changes its growth form. Given the importance of these processes, it is important to know how they are regulated. This study presents a reverse engineering strategy able to infer fullgenomic interaction networks for C. albicans based on a linear regression, utilizing the sparseness criterion (LASSO). To overcome the limited amount of expression data and small number of known interactions, we utilize different prior-knowledge sources guiding the network inference to a knowledge driven solution. Since, no database of known interactions for C. albicans exists, we use a textmining system which utilizes full-text research papers to identify known regulatory interactions. By comparing with these known regulatory interactions, we find an optimal value for global modelling parameters weighting the influence of the sparseness criterion and the prior-knowledge. Furthermore, we show that soft integration of prior-knowledge additionally improves the performance. Finally, we compare the performance of our approach to state of the art network inference approaches.

Salicylhydroxamic Acid Inhibits the Growth of Candida albicans

Candida spp. are common and aggressive pathogens. Because of the growing resistance of Candida spp. to current antifungals, novel targets, found in Candida spp. but not in humans or other flora, have to be identified. The alternative oxidase (AOX) is one such possibility. This enzyme is insensitive to cyanide, but is sensitive to compounds such as salicylhydroxamic acid (SHAM), disulfiram and n-alkyl gallates. The growth Candida albicans was inhibited by SHAM (Ki = 9-15 mM) and cyanide (Ki = 2-4 mM), albeit to differing extents. The rate of O2 uptake was inhibited by less than 10% by 25 mM SHAM and by about 90% by 250 μM KCN. Although SHAM substantially inhibited the growth of C. albicans, it is unlikely that the inhibition of AOX was the cause. Salicylhydroxamic acid is used therapeutically in the treatment of urinary tract infections and urolithiasis, but it also has some potential in the treatment of C. albicans infection.

Evaluation of the Antifungal and Antioxidant Activities of the Leaf Extract of Aloe vera(Aloe barbadensis Miller)

Aloe vera has been used worldwide both for pharmaceutical, food, and cosmetic industries due to the plethora of biological activities of some of its metabolites. The aim of this study was to evaluate the antifungal and antioxidant activities of the leaf extract. The antifungal activity was determined by the agar-well diffusion method against plant and human fungal pathogens. The methanol and ethanol portions of the extracts studied were more bioactive than ethyl acetate portion. It was also observed that the activity was more pronounced on plant pathogen than human pathogen except Candida albicans. This is an indication that the extract has the potential to treat plant fungal infections. The Aloe extract showed the significant antioxidant activity by the DPPH radical scavenging method. Therefore, the Aloe extract provided as natural antioxidant has been used in health foods for medical and preservative purposes.

Induction of Alternative Oxidase Activity in Candida albicans by Oxidising Conditions

Candida albicans ATCC 10231 had low endogenous activity of the alternative oxidase compared with that of C. albicans ATCC 10261. In C. albicans ATCC 10231 the endogenous activity declined as the cultures aged. Alternative oxidase activity could be induced in C. albicans ATCC 10231 by treatment with cyanide, but the induction of this activity required the presence of oxygen which could be replaced, at least in part, with high concentrations of potassium ferricyanide. We infer from this that the expression of the gene encoding the alternative oxidase is under the control of a redoxsensitive transcription factor.