Biology subjects

Lizarraga, A.

Publications and source records attributed to Lizarraga, A..

4 recordsLinked to original sources

bioRxiv2025

Targeting histone acetylation to overcome drug resistance in the parasite Trichomonas vaginalis

Resistance to antimicrobial drugs is a major global health challenge, yet the regulatory mechanisms underlying resistance phenotypes remain incompletely understood. In particular, whether epigenetic processes contribute to antimicrobial resistance in microbial eukaryotes is largely unexplored. Here, we show that epigenetic regulation plays a central role in modulating metronidazole resistance in Trichomonas vaginalis, the causative agent of the most common non-viral sexually transmitted infection. Pharmacological inhibition of histone deacetylases restores drug sensitivity in a highly resistant clinical isolate, markedly reducing the minimum inhibitory concentration. Integrative transcriptomic reveal widespread transcriptional reprogramming associated with activation of pathways involved in redox metabolism, transcriptional regulation, and stress responses. Chromatin profiling demonstrates that increased H3K9 acetylation is strongly associated with transcriptional activation. Upon TSA treatment, increased H3K9 acetylation is observed at promoters and gene bodies of genes that may be associated with MTZ resistance. By combining epigenetic perturbation with comparative transcriptomics across multiple strains, we identify a set of genes that are epigenetically silenced in resistant parasites that are constitutively expressed in sensitive backgrounds. Functional re-expression of two candidates, thioredoxin reductase and a Myb-like transcription factor (Myb6), significantly reduces resistance, establishing a direct link between epigenetic regulation and drug sensitivity. Together, our findings uncover a reversible, chromatin-based mechanism underlying antimicrobial resistance in a protozoan parasite and highlight epigenetic reprogramming as a potential therapeutic strategy. More broadly, this work suggests that epigenetic regulation may represent a general and previously underappreciated layer of control over drug resistance in microbial eukaryotes.

microbiology↗

bioRxiv2024

Improved BOLD Detection with Sliced Inverse Regression

Functional magnetic resonance imaging (fMRI) has been effective in linking task-related brain responses to changes in blood oxygen level density (BOLD). However, its reliance on BOLD measurements makes it vulnerable to artifacts and false-positive signals. Commonly, researchers use many regressors in a General Linear Model to filter true signals, but this adds noise and complicates interpretation. In this paper we suggest using Sliced Inverse Regression (SIR) to simplify covariate dimensionality and identify relevant regressors. We compare a general linear model applied to both original and SIR-adjusted data, demonstrating that SIR improves signal detection, reduces noise, and yields statistically significant results even with conservative measures.

neuroscience↗

bioRxiv2022

Snake Fungal Disease Caused by the Fungal Pathogen Ophidiomyces ophidiicola in Texas

The pathogen Ophidiomyces ophidiicola (O.o.), widely known as the primary cause of snake fungal disease (SFD) has been detected in Texass naive snakes. Our team set out to begin to characterize O. ophidiicolas spread in east Texas. From July 2019 until October 2021, we sampled 176 snakes across east Texas and detected 27 positives cases (qPCR confirmed 27/176). From a ribbon snake with clear clinical display, we isolated and cultured what we believe to be the Texas isolate of O. ophidiicola. With over 1/10 snakes that may be infected in East Texas, gives credence to the onset of SFD in Texas.

microbiology↗

bioRxiv2019

Exploring the link between adenine DNA methylation and 3D genome organization in the parasite Trichomonas vaginalis

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract causing infections that range from asymptomatic to highly inflammatory. Recent works have highlighted the importance of histone modifications in the regulation of transcription and parasite pathogenesis. However, the nature of DNA methylation in the parasite remains unexplored. Using a combination of immunological techniques and UHPLC, we analyzed the abundance of DNA methylation in strains with differential pathogenicity demonstrating that N6-methyladenine (6mA), and not 5-methylcytosine (5mC), is the main DNA methylation mark in T. vaginalis. Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic regions, with a preference for certain super-families of DNA transposable elements. We show that 6mA in T. vaginalis is associated with silencing when present on genes. Interestingly, bioinformatics analysis revealed the presence of transcriptionally active or repressive intervals flanked by 6mA-enriched regions and results from chromatin conformation capture (3C) experiments suggest these 6mA flanked regions are in close spatial proximity. These associations were disrupted when parasites were treated with the demethylation activator ascorbic acid. This finding revealed a new role for 6mA in modulating 3D chromatin structure and gene expression in this divergent member of the Excavata.\n\nSIGNIFICANCE STATEMENTTrichomonas vaginalis causes the most common non-viral sexually transmitted infection yet little is known about the regulation of gene expression in this eukaryotic parasite. We demonstrate that N6-methyladenine (6mA) is the main methylation mark in the T. vaginalis genome. 6mA is widespread in DNA of eubacterial genera, but uncommon in genomes of most eukaryotes. Examination of the genome-wide distribution of 6mA reveals a preference for intergenic regions. Transcriptionally active or repressive intervals are found to be flanked by 6mA-enriched regions and data suggest 6mA flanked regions are in close 3D spatial proximity. Our findings describe for the first time the presence of DNA methylation in T. vaginalis and reveal a new role for 6mA in modulating 3D chromatin architecture.

microbiology↗