Genome-Scale Metabolic Model of the Human Pathogen Candida albicans: A Promising Platform for Drug Target Prediction

Abstract

Candida albicans is one of the most impactful fungal pathogens and the most common cause of invasive candidiasis, which is associated with very high mortality rates. With the rise in the frequency of multidrug-resistant clinical isolates, the identification of new drug targets and new drugs is crucial in overcoming the increase in therapeutic failure. In this study, the first validated genome-scale metabolic model for Candida albicans, iRV781, is presented. The model consists of 1221 reactions, 926 metabolites, 781 genes, and four compartments. This model was reconstructed using the open-source software tool merlin 4.0.2. It is provided in the well-established systems biology markup language (SBML) format, thus, being usable in most metabolic engineering platforms, such as OptFlux or COBRA. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources when compared to experimental data. Finally, this genome-scale metabolic reconstruction was tested as a platform for the identification of drug targets, through the comparison between known drug targets and the prediction of gene essentiality in conditions mimicking the human host. Altogether, this model provides a promising platform for global elucidation of the metabolic potential of C. albicans, possibly guiding the identification of new drug targets to tackle human candidiasis.

Candida albicans—The Virulence Factors and Clinical Manifestations of Infection

“…It is an important mechanism in the enhancement of the virulence of Candida spp. Thigmotropism aids in creating a biofilm on abiotic surfaces and the spread in the host tissue [ 16 ].…”

“…In its metabolism, Candida albicans uses glucose as a source of carbon and amino acids as nitrogen sources [ 16 ].…”

merlinv4.0: an updated platform for the reconstruction of high-quality genome-scale metabolic models

“…The scientific community has extensively used merlin , as corroborated by the multiple published works (32–35, 42, 81, 82) and considerable user-base expansion. The scalability and reliability of merlin 4.0 have been showcased with the reconstruction of multiple models, but particularly with the Quercus suber’ s, which is the first GSMM of a ligneous tree.…”

Enabling rational gut microbiome manipulations by understanding gut ecology through experimentally-evidenced in silico models

“…139 Similarly, GSMs of fungal gut commensals and opportunistic pathogens have emerged in recent years. 140,141 GSM has limited capacity to represent phages, however, as these viruses are not metabolically self-sufficient organisms. ABMs could represent the effects of phage-infection, and other behavior-modifying phenomena such as horizontal gene transfer (HGT).…”