Biology subjects

Lopez-Garcia, A.

Publications and source records attributed to Lopez-Garcia, A..

5 recordsLinked to original sources

bioRxiv2026

Recreational climbing alters cliff soil chemistry and plant-associated fungal communities

O_LICliffs are environmentally extreme yet biodiversity-rich ecosystems that harbour specialist plants, many endemic and threatened. Plant persistence in these nutrient-poor substrates may depend on tightly linked soil- and root-associated microbial communities, which remain poorly understood. These interactions may become increasingly important with the global expansion of recreational climbing. While physical climbing impacts on vegetation are documented, potential chemical effects, from the use of climbing chalk (magnesium carbonate), on soil properties and plant-associated microbiota remain unknown. C_LIO_LIWe sampled soils and roots beneath cliff-specialist and generalist plants, and unvegetated soils, across climbed and unclimbed routes in northern, central, and southern Spain. Soil physicochemical properties were quantified, fungal communities were characterized using ITS-metabarcoding, and structural equation modelling was used to disentangle direct and indirect effects. C_LIO_LIClimbing increased soil pH and altered soil chemical properties, driving shifts in fungal diversity and functional composition in soil and roots. The relative read abundance of root-associated symbiotrophic fungi declined, whereas arbuscular mycorrhizal fungi and pathogens increased in climbed cliffs. Overall effects were consistent, with cliff-specialist plants mediating nutrient and fungal shifts. C_LIO_LIur findings show that climbing can reshape cliff soil chemistry and fungal communities, with potential cascading consequences for plant functional performance, nutrient dynamics, and ecosystem resilience. C_LI

ecology↗

bioRxiv2026

Metabolic commitment and nitrogen control of diazotrophy in the diazoplast-containing diatom Epithemia adnata

Earths nitrogen cycle is central to sustaining ecosystem productivity and global biogeochemical balance. Although biological N2-fixation is well characterized in prokaryotes and plant symbioses, in other eukaryotic lineages it remains poorly understood. Diatoms of the family Rhopalodiacea harbor diazoplasts, endosymbiotic spheroid bodies specialized for N2-fixation. This makes these diatoms genuine N2-fixing eukaryotes that represent a unique model for organelle evolution, parallel but distinct from haptophyte nitroplasts. Here, we report the isolation and stable cultivation of an Epithemia adnata strain, the sequencing of its diazoplast genome and its proteomic profile when growing diazotrophically in the light or darkness, or upon exposure to ammonium. Our analyses reveal that ammonium induced broad down-regulation of diazoplast proteins, particularly those linked to N2-fixation, ATP synthesis, and central carbon metabolism underscoring a general regulatory commitment toward diazotrophic metabolism tightly coupled to host carbon and nitrogen status. The pentose phosphate pathway and ferredoxin-NADP oxidoreductase appear as likely source of reductant to nitrogenase. A striking enrichment of chaperones, peroxiredoxins, bacterioferritin-like proteins, and DpsA might stabilize nitrogenase and buffer against oxidative stress during light-driven diazotrophy. Importantly, we identified a plasmid-encoded GlpF as a putative glycerol transporter, pointing to glycerol-mediated host-symbiont metabolic integration in the extant symbiosis and possibly a crucial innovation during the early evolutionary stages of its establishment. Thus, diazoplast activity is not autonomous but requires integration with host carbon and nitrogen status, establishing glycerol transport, reductant supply, stress mitigation, and nutrient-responsive regulation as pivotal mechanisms of nitrogenase activity and host integration. These findings have broad implications for biogeochemical cycling, organellogenesis, and synthetic biology strategies aimed at engineering N2-fixation in crop plants. SignificanceN2-fixing eukaryotes are increasingly recognized as abundant algae containing bacterial-derived diazotrophic endosymbionts, representing an underappreciated component of global N cycling. Diazoplasts in rhopalodiacean diatoms represent a compelling example of such endosymbionts specialized for N2-fixation. By combining genomic sequencing and proteomic analysis, we demonstrate their metabolic specialization, host integration, and regulatory commitment to diazotrophy. These findings reinforce the emerging view that diazoplasts function as organelle-like entities dedicated to N2-fixation, dependent on host-supplied carbon while contributing fixed N in return. Beyond giving evolutionary insights into organellogenesis, this work establishes a framework for translational applications, such as engineering N2-fixation into agricultural plants. Such advances could reduce reliance on synthetic fertilizers, influence biogeochemical cycles, and promote sustainable food production.

plant biology↗

bioRxiv2025

A TARGETED COMBINATION THERAPY ACHIEVES EFFECTIVE PANCREATIC CANCER REGRESSION AND PREVENTS TUMOR RESISTANCE

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest cancer survival rates. Recent studies using RAS(ON) inhibitors as single agents have opened the door to more efficacious therapies. Here, we demonstrate that genetic ablation of three independent nodes involved in downstream (RAF1), upstream (EGFR) and orthogonal (STAT3) KRAS signaling pathways leads to complete and permanent disappearance of orthotopic PDACs induced by KRAS/TP53 mutations. Likewise, a combination of RAS(ON) (RMC-6236/daraxonrasib), EGFR family (afatinib) and STAT3 (SD36) selective inhibitors/degraders induced the effective regression of these orthotopic tumors with no evidence of tumor resistance for over 200 days post-treatment. This combination therapy also led to significant regression of genetically engineered mouse tumors as well patient-derived tumor xenografts (PDX) in the absence of tumor relapses. Finally, this combination therapy was well tolerated by the animals. These results should guide the development of clinical trials that could benefit PDAC patients.

cancer biology↗

bioRxiv2024

On the ecology of Acinetobacter baumannii - jet stream rider and opportunist by nature

The natural reservoirs of the nosocomial pathogen Acinetobacter baumannii are not well defined. We previously identified white storks as a model system to study the ecology of A. baumannii. Having screened more than 1,300 white stork nestlings over a period of six years across different regions of Poland and Germany (overall isolation rate of [~]29.5%), including food chain analyses and environmental samplings, we come up with a detailed picture of the dynamics and diversity of A. baumannii in their natural habitats. Adult storks, rather than being stably colonized with strains of A. baumannii which are successively transferred to their offspring, instead initially encounter these bacteria while foraging. Among their common food sources, consisting of earthworms, small mammals, and insects, we identified earthworms as a potential source of A. baumannii, but more so the associated soil as well as plant roots. Through this, hotspot soil and compost habitats were identified which enable population dynamics to be studied over the course of the year. We demonstrate that sterilized plant material is rapidly colonized by airborne A. baumannii suggesting they patrol to search for novel habitats, being opportunist by nature. The prevalence of A. baumannii exhibited a strong seasonality and peaked during summer. The strains we collected in Poland and Germany represent more than 50% of the worldwide known diversity in terms of the intrinsic OXA-51-like {beta}-lactamase. A set of [~]400 genomes was determined and compared to a diverse set of publicly available genomes. Our pan-genome estimate of the species ([~]51,000 unique genes) more than doubles the amount proposed by previous studies. Core-genome based phylogenetic analyses illustrated numerous links between wildlife isolates and hospital strains, including ancient as well as recent intercontinental transfer. Our data further suggest massive radiation within the species early after its emergence, matching with human activity during the Neolithic. Deforestation in particular seemed to set the stage for this bloom as we found that forests do not provide conducive conditions for the proliferation of A. baumannii. In contrast, wet and nutrient-rich soil alongside rivers sampled during the summer can yield an isolation rate of [~]30%. Linking published work on the interaction between A. baumannii and fungi and on aspergillosis as a major cause of mortality in white stork nestlings to our findings, we hypothesized that fungi and A. baumannii share a long history of coevolution. Interaction studies revealed the capability of A. baumannii to adhere to fungal spores and to suppress spore germination. Taken together, the intrinsic resistance endowment and potential to acquire antibiotic resistance can be explained by coevolution with antibiotic-producing fungi and other microorganisms within soil, and resistance to desiccation stress and radiation can be interpreted in the light of intercontinental hitchhiking through fungal spores. Originality - SignificanceThe ecology of the nosocomial pathogen Acinetobacter baumannii remains poorly understood outside the hospital. Here, we present the most comprehensive study on its environmental biology to date, after having collected more than 1,450 independent isolates of which around 400 were whole genome-sequenced. This study more than doubles the size of the pan-genome of the species, illustrating both the diversity of our collection and the bias of previous work, but also the bottleneck for the establishment of lineages within the hospital environment. We reached isolation rates of about 30% both in white stork (Ciconia ciconia) nestlings and in soil samples when considering for sampling all preferences of A. baumannii we uncovered. Thus, it is now possible to study the ecology and evolution of A. baumannii in nature at an unprecedented temporal and spatial resolution. We describe the worldwide spread of A. baumannii lineages in nature as an ancient phenomenon that even surpasses that of human-associated bacteria in magnitude. This is likely due to airborne spread, putatively facilitated by association with fungal spores. We propose that A. baumannii is an opportunist by nature, using airborne patrolling to rapidly enter new suitable habitats consisting of organic matter in early stages of decomposition. Our collective data suggest that A. baumannii, early after its speciation, went through massive radiation during the Neolithic, likely due to deforestation, settlement and farming producing numerous favorable habitats. Their natural lifestyle, which requires rapid adaptability to various habitats as well as tolerance to desiccation, radiation and antibiotic stress, perfectly predispose these opportunistic pathogens to establish within the hospital setting. Comparison of genomes from environmental and clinical isolates will now enable studies of the adaptive evolution of environmental bacteria towards multidrug-resistant opportunistic pathogens.

microbiology↗

bioRxiv2023

CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel driver of metastasis in prostate cancer

Owing to the inefficacy of available treatments, the survival rate of patients with metastatic prostate cancer (mPCa) is severely decreased. Therefore, it is crucial to identify new therapeutic targets to increase their survival. This study aim was to identify the most relevant regulators of mPCa onset by performing two high-throughput CRISPR/Cas9 screenings. Furthermore, some of the top hits were validated using small interfering RNA (siRNA) technology, with protein arginine methyltransferase 7 (PRMT7) being the best candidate. Its inhibition or depletion via CRISPR significantly reduced mPCa cell capacities in vitro. Moreover, PRMT7 ablation reduced mPCa appearance in chicken chorioallantoic membrane and mouse xenograft assays. Molecularly, PRMT7 reprograms the expression of several adhesion molecules through methylation of several transcription factors, such as FoxK1 or NR1H2, which results in primary tumor PCa cell adhesion loss and motility gain. Importantly, PRMT7 is upregulated in advanced stages of Spanish PCa tumor samples and PRMT7 pharmacological inhibition reduces the dissemination of mPCa cells. Thus, here is shown that PRMT7 is a potential therapeutic target and biomarker of mPCa.

cancer biology↗