Biology subjects

Anguita, J.

Publications and source records attributed to Anguita, J..

6 recordsLinked to original sources

bioRxiv2026

Motile bacteria collectively transport soil water during host colonisation

Nutrient availability in soil is temporally and spatially heterogeneous, and, as a result, microbial migration is critical for many species. The nature of microbial movement in soil, however, is unknown due to a lack of observations and experimental data. We developed live-imaging and image-analysis techniques to track the movement of single cells through soil to elucidate how Bacillus subtilis utilises pore space during the early root colonisation. The study reveals that the bacterium can modify fluid pathways to create streams, even at low bulk cell density. The phenomenon was influenced by pore structure, distance from the root and the viscosity of the soil solution. By generating macroscopic fluid motion, bacteria may also be able to travel faster and farther than individually, while limiting energy expenditure.

microbiology↗

bioRxiv2026

Surface potential as a strong early osteogenic trigger via mechanotransduction and calcium accumulation

Analyzing the differentiation potential of cells in contact with newly developed materials is essential for assessing their ability to integrate into biological tissues and promote functional regeneration. Material properties such as rigidity, topography, and wettability significantly influence stem cell differentiation and are therefore optimized in implants. In this context, surface potential has been repeatedly, albeit inadvertently, shown to enhance osteogenesis. Here, we demonstrate that this surface property modulates cellular mechanosensing by altering the cells perception of substrate rigidity. Specifically, we show that human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on surfaces with a net zero charge, coated with collagen type I, exhibit characteristics typical of cells adhering to compliant substrates. Conversely, mesenchymal stem cells on polarized surfaces activate mechanoresponsive pathways that promote osteogenesis, as evidenced by large spreading areas, enhanced contractility, and Yes-associated protein (YAP) translocation into the nucleus. Furthermore, our data suggest that negative net surface potentials lead to the local accumulation of calcium ions, which further facilitates osteogenic differentiation. Collectively, our findings reveal that biomaterials surface potential, a previously uncharacterized mediator of cellular mechanotransduction, should be considered in the design of next-generation biomaterials for tissue regeneration applications.

cell biology↗

bioRxiv2025

Candida albicans enhances melanoma cell aggressiveness through p38-MAPK and HIF-1α pathways and metabolic reprogramming

Recent studies have increasingly focused on the role of fungi, including Candida albicans, in carcinogenesis. Since C. albicans is a component of the human microbiota, particularly on the skin, we investigated its effect on the phenotype and signalling pathways of melanoma cells. Assays for migration, adhesion, angiogenesis, and hepatic metastasis showed that C. albicans promotes a more malignant phenotype in melanoma cells. At the transcriptomic level, C. albicans increased the expression of VEGF (Vegfa), and genes associated with MAPK and HIF-1 signalling pathways, and with aerobic glycolysis. Further in vitro analysis revealed that TLRs and EphA2 receptors are involved in the recognition of live C. albicans, stimulating VEGF secretion and expression of the AP-1 transcription factor component c-Fos through p38-MAPK and HIF-1. These pathways also regulate the expression of other AP-1 constituents such as Atf3, Jun, and Jund. Moreover, p38-MAPK regulates glycolytic genes like Hk2, Slc2a1, and Eno2. In conclusion, C. albicans activates the p38-MAPK/c-Fos/AP-1 and HIF-1/HIF-1/c-Fos/AP-1 pathways in melanoma cells, promoting a pro-angiogenic environment and metabolic reprogramming. Therefore, this study clarifies the impact of C. albicans on melanoma cells, which can lead to the use of antifungal therapies as complementary to traditional treatments for melanoma.

microbiology↗

bioRxiv2024

Mitochondrial dysfunction: unraveling the elusive biology behind anti-TNF response during ulcerative colitis

BackgroundRecent studies hint at mitochondrial genes influencing UC patient response to anti-TNF treatment. We evaluated this hypothesis by following a targeted strategy to identify gene expression that captures the relationship between mitochondrial dysregulation and response to treatment. Our objective was to initially examine this relationship in colon samples and subsequently assess whether the resulting signal persists in the bloodstream. MethodsWe analyzed the transcriptome of colon samples from an anti-TNF treated murine model characterized by impaired mitochondrial activity and treatment resistance. We then transferred the findings that linked mitochondrial dysfunction and compromised treatment response to an anti-TNF treated UC human cohort. We next matched differential expression in the blood using monocytes from peripheral blood of controls and IBD patients, and we evaluated a classification process at baseline with whole blood samples from UC patients. ResultsIn human colon samples, the derived gene-set from the murine model showed differential expression, primarily enriched metabolic pathways, and exhibited similar classification capacity as genes enriching inflammatory pathways. Moreover, the evaluation of the classification signal using blood samples from UC patients at baseline highlighted the involvement of mitochondrial homeostasis in treatment response. ConclusionOur results highlight the involvement of metabolic pathways and mitochondrial homeostasis in determining treatment response and their ability to provide promising classification signals with detection levels in both colon and bloodstream.

immunology↗

bioRxiv2021

Bovine neutrophils release extracellular traps and cooperate with macrophages in Mycobacterium avium subsp. paratuberculosis clearance

Mycobacterium avium subsp. paratuberculosis (Map) is the underlying pathogen causing bovine paratuberculosis (PTB), an enteric granulomatous disease that mainly affects ruminants and for which an effective treatment is needed. Macrophages are the primary target cells for Map, which survives and replicates intracellularly by inhibiting phagosome maturation. Neutrophils are present at disease sites during the early stages of the infection, but seem to be absent in the late stage, in contrast to healthy tissue. Although neutrophil activity has been reported to be impaired following Map infection, their role in PTB pathogenesis has not been fully defined. Neutrophils are capable of releasing extracellular traps consisting of extruded DNA and proteins that immobilize and kill microorganisms, but this mechanism has not been evaluated against Map. Our main objective was to study the interaction of neutrophils with macrophages during an in vitro mycobacterial infection. For this purpose, neutrophils and macrophages from the same animal were cultured alone or together in the presence of Map or Mycobacterium bovis Bacillus-Calmette-Guerin (BCG). Extracellular trap release, mycobacteria killing as well as IL-1{beta} and IL-8 release were assessed. Neutrophils released extracellular traps against mycobacteria when cultured alone and in the presence of macrophages without direct cell contact, but resulted inhibited in direct contact. Macrophages were extremely efficient at killing BCG, but ineffective at killing Map. In contrast, neutrophils showed similar killing rates for both mycobacteria. Co-cultures infected with Map showed the expected killing effect of combining both cell types, whereas co-cultures infected with BCG showed a potentiated killing effect beyond the expected one, indicating a potential synergistic cooperation. In both cases, IL-1{beta} and IL-8 levels were lower in co-cultures, suggestive of a reduced inflammatory reaction. These data indicate that cooperation of both cell types can be beneficial in terms of decreasing the inflammatory reaction while the effective elimination of Map can be compromised. These results suggest that neutrophils are effective at Map killing and can exert protective mechanisms against Map that seem to fail during PTB disease after the arrival of macrophages at the infection site.

immunology↗

bioRxiv2020

Dynamin-like proteins are essential for vesicle biogenesis in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) secretes pathogenicity factors and immunologically active molecules via membrane vesicles. However, nothing is known about the mechanisms involved in mycobacterial vesicle biogenesis. This study investigates molecular determinants of membrane vesicle production in Mtb by analyzing Mtb cells under conditions of high vesicle production: iron limitation and VirR restriction. Ultrastructural analysis showed extensive cell envelope restructuring in association with vesicle release that correlated with downregulation of cell surface lipid biosynthesis and peptidoglycan alterations. Comparative transcriptomics showed common upregulation of the iniBAC operon in association with high vesicle production in Mtb cells. Vesicle production analysis demonstrated that the dynamin-like proteins (DLPs) encoded by this operon, IniA and IniC, are necessary for release of EV by Mtb in culture and in infected macrophages. Isoniazid, a first-line antibiotic, used in tuberculosis treatment, was found to stimulate vesicle release in a DLP-dependent manner. Our results provide a new understanding of the function of mycobacterial DLPs and mechanistic insights into vesicle biogenesis. The findings will enable further understanding of the relevance of Mtb-derived extracellular vesicles in the pathogenesis of tuberculosis and may open new avenues for therapeutic research. IMPORTANCEIron is an essential nutrient that promotes survival and growth of M. tuberculosis, the bacterium that causes human tuberculosis (TB). Limited availability of iron, often encountered in the host environment, stimulates M. tuberculosis to secrete membrane-bound extracellular vesicles containing molecules that may help it evade the immune system. Characterizing the bacterial factors and mechanisms involved in the production of mycobacterial vesicles is important for envisioning ways to interfere with this process. Here, we report the discovery of proteins required by M. tuberculosis for vesicle biogenesis in culture and during host cell infection. We also demonstrate a connection between antibiotic response and extracellular vesicle production. The work provides insights into the mechanisms underlying vesicle biogenesis in M. tuberculosis and permits better understanding of the significance of vesicle production to M. tuberculosis-host interactions and antibiotic stress response.

microbiology↗