Biology subjects

Perez-Cuesta, U.

Publications and source records attributed to Perez-Cuesta, U..

3 recordsLinked to original sources

bioRxiv2026

Biotinylation-dependent near-neighbor analysis for identification of septation regulators in Aspergillus fumigatus

Recent work has established septation as a critical process for virulence in A. fumigatus, as strains lacking septa are avirulent. While our work has focused on the well-studied Septation Initiation Network (SIN), understanding of septation machinery upstream and downstream of SIN remains limited in filamentous fungi. Proximity labeling techniques are powerful tools to study pathway interactions, especially those that are transient. Recent advances have seen TurboID used to study pathways and processes important for fungal pathogenesis. In this study, we adapt TurboID for use in Aspergillus fumigatus and use overlapping datasets of two SIN components, the terminal NDR kinase SidB and its binding partner MobA, to identify putative septation effectors. Many known septation effectors, including septins and cell wall synthesis proteins, were enriched in our datasets, validating the approach. Phenotypic characterization of hits identified by LC-MS/MS revealed several previously uncharacterized gene products involved in septum formation and cell wall stress tolerance. These included the PP2A regulatory subunit PabA and IQGAP SepG, which have been shown to regulate septation in Aspergillus nidulans. Thus, TurboID is a useful tool to study fungal signaling and physiology in A. fumigatus and may be used to improve understanding of pathogenic processes.

microbiology↗

bioRxiv2024

The oxidative stress response-related peroxiredoxin Tsa1b of Candida auris functions as a virulence factor that promotes infection

The difficulty of accurately identifying Candida auris and the high resistance rates presented have increased the concern in the healthcare setting. Due to this, the aim of this study was to analyse the fungal response to oxidative stress. To achieve this goal, gene and protein expression were examined using qPCR and two-dimensional electrophoresis, respectively, peroxiredoxin Tsa1b being discovered to be overexpressed under oxidative stress. Besides, its antigenicity was also confirmed by western blotting. Subsequently, the significance of Tsa1b was next investigated by creating and characterizing the C. auris {Delta}TSA1B and C. auris {Delta}TSA1B::TSA1B strains using CRISPR-Cas9. The findings demonstrated that the{Delta} TSA1B strain was more susceptible to oxidative and cell wall stressors than the wild-type strain, which was consistent with an increase in the cell wall {beta}-glucan amounts when grown in the presence of oxidative stress. Furthermore, the{Delta} TSA1B strain was also more vulnerable to the presence of dendritic cells and bone marrow-derived macrophages. Finally, in vivo infections performed in Galleria mellonella and mice showed a slower progression of the disease in those animals infected with the mutant strain. In conclusion, the peroxiredoxin Tsa1b has been identified as an important protein for the C. auris response to oxidative stress and as a virulence factor, allowing for a more thorough knowledge of the pathobiology of this yeast. This study points out the potential that this protein may have for the development of new diagnostic and therapeutic approaches. HIGHLIGHTSO_LISeveral metabolic proteins are implicated in C. auris response to oxidative stress C_LIO_LIC. auris response to oxidative stress is influenced by the Tsa1b peroxiredoxin C_LIO_LILack of Tsa1b generates more susceptibility to stresses and an altered cell wall C_LIO_LIC. auris Tsa1b is involved in the fungal interaction with host immune cells C_LIO_LIThe Tsa1b of C. auris contributes to the progression of the infection in vivo C_LI

microbiology↗

bioRxiv2023

The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulence.

In this study, two distinct in vitro infection models of Aspergillus fumigatus, using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubated Aspergillus uncovered 140 fungal genes up-regulated in common between both models that, when compared with a previously published in vivo transcriptomic study, allowed the identification of 13 genes consistently up-regulated in all three infection conditions. Among them, the maiA gene, responsible for a critical step in the L-phenylalanine degradation pathway, was identified. Disruption of maiA resulted in a mutant strain unable to complete the Phe degradation pathway, leading to an excessive production of pyomelanin when this amino acid served as the sole carbon source. Moreover, the disruption mutant exhibited noticeable cell wall abnormalities, with reduced levels of {beta}-glucans within the cell wall. the maiA-1 mutant strain induced reduced inflammation in primary macrophages and displayed significantly lower virulence in a neutropenic mouse model of infection. This is the first study linking the A. fumigatus maiA gene to fungal cell wall homeostasis and virulence.

microbiology↗