Victor Arribas

Scopus Publications

Omics and Multiomics-Based Diagnostics for Invasive Candidiasis: Toward Precision Medicine
Aida Pitarch, Víctor Arribas, Concha Gil
Molecular and Cellular Proteomics, 2025
Invasive candidiasis (IC) is a serious, life-threatening, and costly fungal infection if not diagnosed early and treated appropriately. However, this healthcare-associated mycosis caused by Candida spp. is difficult to diagnose because of its nonspecific clinical signs and symptoms, and the lack of early and accurate detection methods. IC is also difficult to treat due to its late diagnosis, the limited antifungal arsenal, and the rapid emergence and spread of (multi)drug-resistant Candida strains. Therefore, early and accurate innovative methods for species and resistance identification in IC (candidemia and deep-seated candidiasis) are urgently needed to initiate timely and appropriate antifungal therapy, and reduce its high morbidity, mortality, and health care costs in hospitalized patients (especially, severely immunocompromised or critically ill patients). The availability of the complete genome sequences of the most clinically relevant Candida species coupled with recent advances in high-throughput omics technologies have spurred an unprecedented era in the discovery and development of IC diagnostics at different levels of molecular complexity. Here, we review the contribution of current and emerging omics technologies, including genomics, transcriptomics, proteomics, peptidomics, metabolomics, lipidomics, glycomics, immunomics (immunoproteomics, immunopeptidomics, and immunoglycomics), imiomics (imaging-omics), and microbiomics (metagenomics, metatranscriptomics, metaproteomics, and metabonomics), to the process of biomarker development for early diagnosis, antifungal susceptibility, prognosis, follow-up, and therapeutic monitoring in IC. We highlight the potential of integrating multiple omic data (through integromics, multiomics, or panomics, together with systems biology and artificial intelligence) for the discovery of multidimensional biomarker signatures and computational algorithms for IC diagnosis. Finally, we discuss future challenges and prospects for their clinical implementation. These next-generation IC diagnostics promise to revolutionize medical practice by unraveling the complexity of biological systems at multiple levels. Furthermore, these could help clinicians make more precise and personalized clinical decisions through multiomics or panomics-based precision medicine approaches, rather than traditional one-size-fits-all approaches.
Integrative Phosphoproteomic and Proteomic Analysis of Candida albicans Exposed to Oxidative Stress
Víctor Arribas, Ana Borrajo, María Luisa Hernáez, Raquel Martínez, Lucía Monteoliva, Concha Gil, Gloria Molero
Journal of Proteome Research, 2025
Candida albicans is an opportunistic pathogen, which has recently been included in the high-priority list of pathogenic fungi by the World Health Organization (WHO). The scarce arsenal available to treat such invasive fungal infections makes the discovery of new antifungal targets an important task. This study utilizes DDA-MS technology to investigate both the phosphoproteomics and proteomics of C. albicans during its late-stage response to oxidative stress induced by H2O2, aiming to identify key proteins involved. Phosphorylation, as an important post-translational modification, plays a crucial role in the ability of C. albicans to survive oxidative stress. Our study enabled the identification and quantification of important changes in both protein abundance and phosphorylation events across multiple proteins following a 200 min 10 mM H2O2 treatment. The use of the DDA-MS approach allowed for the identification of new actors in the response to oxidative stress. Novel phosphorylation sites were identified in kinases and transcription factors. Regarding protein kinases, Cdc5-reduced phosphorylation may mediate a transient G2 cell cycle arrest, while Kis1─the regulatory β-subunit of Snf1 kinase─might play a role in ROS scavenging following oxidative stress. In terms of transcription factors, Gzf3-decreased phosphorylation was essential for cell survival and ROS detoxification after oxidative stress.
Deciphering the oxidative stress response in Candida albicans
Víctor Arribas, Concha Gil, Gloria Molero
Fungal Biology Reviews, 2025
Candida species are the leading cause of invasive fungal infections, with Candida albicans being the most common one. Consequently, the World Health Organization has included C. albicans in its fungal priority pathogens list. Following infection, phagocytes (mostly macrophages) initiate a respiratory burst, producing oxidant compounds, such as hydrogen peroxide. In response, C. albicans activates a robust oxidative stress response to catalyze the oxidant molecules produced by the immune system and counteract their oxidative effects within the cell. The oxidative stress response of C. albicans implies proteomic changes, both in abundance and in post-translational modifications, that are not fully described yet. Proteins with immediate antioxidant properties, the MAPK signaling pathways, and transcription factors are involved in the response. In this review, we discuss the role of these factors and the interactions among them in C. albicans. Many of these mechanisms act as virulence traits that favor the invasive candidiasis and can be used as potential targets for antifungal drugs. • Phagocytes use oxidative stress to destroy Candida albicans during infection. • C. albicans counteracts phagocyte attacks with a robust oxidative stress response. • HOG MAPK pathway and Cap1 are the main actors in anti-oxidative signaling. • Catalase, thioredoxin, and glutathione are the major ROS scavenging systems. • Studying the oxidative stress response may reveal new antifungal targets.
Unravelling the Role of Candida albicans Prn1 in the Oxidative Stress Response through a Proteomics Approach
Victor Arribas, Lucia Monteoliva, María Luisa Hernáez, Concha Gil, Gloria Molero
Antioxidants, 2024
Candida albicans Prn1 is a protein with an unknown function similar to mammalian Pirin. It also has orthologues in other pathogenic fungi, but not in Saccharomyces cerevisiae. Prn1 highly increases its abundance in response to H2O2 treatment; thus, to study its involvement in the oxidative stress response, a C. albicans prn1∆ mutant and the corresponding wild-type strain SN250 have been studied. Under H2O2 treatment, Prn1 absence led to a higher level of reactive oxygen species (ROS) and a lower survival rate, with a higher percentage of death by apoptosis, confirming its relevant role in oxidative detoxication. The quantitative differential proteomics studies of both strains in the presence and absence of H2O2 indicated a lower increase in proteins with oxidoreductase activity after the treatment in the prn1∆ strain, as well as an increase in proteasome-activating proteins, corroborated by in vivo measurements of proteasome activity, with respect to the wild type. In addition, remarkable differences in the abundance of some transcription factors were observed between mutant and wild-type strains, e.g., Mnl1 or Nrg1, an Mnl1 antagonist. orf19.4850, a protein orthologue to S. cerevisiae Cub1, has shown its involvement in the response to H2O2 and in proteasome function when Prn1 is highly expressed in the wild type.
Paxillin-Mediated Recruitment of Calcineurin to the Contractile Ring Is Required for the Correct Progression of Cytokinesis in Fission Yeast
Rebeca Martín-García, Victor Arribas, Pedro M. Coll, Mario Pinar, Raul A. Viana, Sergio A. Rincón, Jaime Correa-Bordes, Juan Carlos Ribas, Pilar Pérez
Cell Reports, 2018
Paxillin is a scaffold protein that participates in focal adhesion signaling in mammalian cells. Fission yeast paxillin ortholog, Pxl1, is required for contractile actomyosin ring (CAR) integrity and collaborates with the β-glucan synthase Bgs1 in septum formation. We show here that Pxl1's main function is to recruit calcineurin (CN) phosphatase to the actomyosin ring; and thus the absence of either Pxl1 or calcineurin causes similar cytokinesis defects. In turn, CN participates in the dephosphorylation of the Cdc15 F-BAR protein, which recruits and concentrates Pxl1 at the CAR. Our findings suggest the existence of a positive feedback loop between Pxl1 and CN and establish that Pxl1 is a crucial component of the CN signaling pathway during cytokinesis.