Biology subjects

Bautista, M. A.

Publications and source records attributed to Bautista, M. A..

3 recordsLinked to original sources

bioRxiv2024

Targeting mechanistic target of rapamycin complex 2 attenuates immunopathology in Systemic Lupus Erythematosus

ObjectiveWe aim to explore the role of mechanistic target of rapamycin complex (mTORC) 2 in systemic lupus erythematosus (SLE) development, the in vivo regulation of mTORC2 by type I interferon (IFN) signaling in autoimmunity, and to use mTORC2 targeting therapy to ameliorate lupus-like symptoms in an in vivo lupus mouse model and an in vitro coculture model using human PBMCs. MethodWe first induced lupus-like disease in T cell specific Rictor, a key component of mTORC2, deficient mice by topical application of imiquimod (IMQ) and monitored disease development. Next, we investigated the changes of mTORC2 signaling and immunological phenotypes in type I IFNAR deficient Lpr mice. We then tested the beneficial effects of anti-Rictor antisense oligonucleotide (Rictor-ASO) in a mouse model of lupus: MRL/lpr mice. Finally, we examined the beneficial effects of RICTOR-ASO on SLE patients PBMCs using an in vitro T-B cell coculture assay. ResultsT cell specific Rictor deficient mice have reduced age-associated B cells, plasma cells and germinal center B cells, and less autoantibody production than WT mice following IMQ treatment. IFNAR1 deficient Lpr mice have reduced mTORC2 activity in CD4+ T cells accompanied by restored CD4+ T cell glucose metabolism, partially recovered T cell trafficking, and reduced systemic inflammation. In vivo Rictor-ASO treatment improves renal function and pathology in MRL/lpr mice, along with improved immunopathology. In human SLE (N = 5) PBMCs derived T-B coculture assay, RICTOR-ASO significantly reduce immunoglobulin and autoantibodies production (P < 0.05). ConclusionTargeting mTORC2 could be a promising therapeutic for SLE.

immunology↗

bioRxiv2024

Novel oil-associated bacteria in Arctic seawater exposed to different nutrient biostimulation regimes

The Arctic Ocean is an oligotrophic ecosystem facing escalating threats of oil spills as ship traffic increases owing to climate change-induced sea ice retreat. Biostimulation is an oil spill mitigation strategy that involves introducing bioavailable nutrients to enhance crude oil biodegradation by endemic oil-degrading microbes. For bioremediation to offer a viable response for future oil spill mitigation in extreme Arctic conditions, a better understanding of the effects of nutrient addition on Arctic marine microorganisms is needed. Comprehensive population tracking of controlled oil-spill microcosms using cell counting and microbial biodiversity screening revealed a significant decline in community diversity together with changes in microbial community composition. These shifts were also indicative of changes in prevailing genomic traits as inferred from 16S rRNA taxonomy of resulting communities. In addition to well-recognized hydrocarbonoclastic bacteria, differential abundance analysis highlighted significant enrichment of unexpected genera Lacinutrix, Halarcobacter and Candidatus Pseudothioglobus. These groups have not been associated with hydrocarbon biodegradation until now, even though genomes from closely related isolates confirm the potential for hydrocarbon metabolism. These findings broaden understanding of marine oil spill bioremediation and how Arctic marine microbiomes and their novel lineages can respond to nutrient biostimulation as a strategy for oil spill mitigation. ImportanceA comprehensive characterization and understanding of the impact of marine bioremediation strategies in the Arctic is crucial for effectively managing oil contamination. Such understanding enables an evaluation of the ecological impacts associated with mitigation strategies to minimize negative effects on sensitive ecosystems. By introducing external nutrients into areas affected by spills, microbial growth can be stimulated, enhancing hydrocarbon degradation by naturally occurring oil-degrading microorganisms. This may include novel microbial groups in permanently cold Arctic waters, where fewer oil biodegradation studies have been performed. It is also important to consider how nutrient addition may affect endemic microbial communities after successful remediation has occurred in oil-contaminated zones. Promoting naturally occurring oil-degrading microorganisms may have significant implications on nutrient cycling and marine food webs, which are critical for sustaining the health and well-being of coastal Indigenous communities in northern latitudes.

microbiology↗

bioRxiv2021

CANT-HYD: A curated database of phylogeny-derived Hidden Markov Models for annotation of marker genes involved in hydrocarbon degradation

Discovery of microbial hydrocarbon degradation pathways has traditionally relied on laboratory isolation and characterization of microorganisms. Although many metabolic pathways for hydrocarbon degradation have been discovered, the absence of tools dedicated to their annotation makes it difficult to identify the relevant genes and predict the hydrocarbon degradation potential of microbial genomes and metagenomes. Furthermore, sequence homology between hydrocarbon degradation genes and genes with other functions often results in misannotation. A tool that systematically identifies hydrocarbon metabolic potential is therefore needed. We present the Calgary approach to ANnoTating HYDrocarbon degradation genes (CANT-HYD), a database containing HMMs of 37 marker genes involved in anaerobic and aerobic degradation pathways of aliphatic and aromatic hydrocarbons. Using this database, we show that hydrocarbon metabolic potential is widespread in the tree of life and identify understudied or overlooked hydrocarbon degradation potential in many phyla. We also demonstrate scalability by analyzing large metagenomic datasets for the prediction of hydrocarbon utilization in diverse environments. To the best of our knowledge, CANT-HYD is the first comprehensive tool for robust and accurate identification of marker genes associated with aerobic and anaerobic hydrocarbon degradation.

bioinformatics↗