Biology subjects

Martinez-Martinez, S.

Publications and source records attributed to Martinez-Martinez, S..

6 recordsLinked to original sources

bioRxiv2026

Paired viromics resolves the modular ecological architecture of the swine nasopharyngeal phageome

BackgroundBacteriophages are recognized modulators of microbiome composition and function, yet their role in the porcine upper respiratory tract, a primary gateway for pathogen colonization in the post-weaning period, remains unexplored. Unlike the porcine gut, no reference framework is available for respiratory sites. Furthermore, the low-biomass nature of nasopharyngeal specimens makes virome recovery highly sensitive to extraction strategy, but the extent to which workflow choice shapes ecological inference in this niche has not been evaluated. ResultsWe profiled the nasopharyngeal phageome of post-weaning piglets across ten commercial farms (30 pen-level pools) using paired DNA-microbiome (DNA-m) and virus-like particle-enriched (VLP-e) short-read metagenomics (n = 60 libraries). Protocol choice strongly reshaped viral recovery (PERMANOVA R{superscript 2} = 0.448, p < 0.0001), with a contig overlap between workflows of <1%. DNA-m favored assembly contiguity, while VLP-e maximized viral detection. By integrating both approaches, we constructed a curated catalogue of 2,501 non-redundant viral operational taxonomic units (vOTUs), with only 5.2% showing similarity to known phages, underscoring the extensive novelty of this niche. Ecologically, within the integrated community dataset (n = 4,357), predicted replication strategy emerged as a dominant organizing axis: lifestyle explained up to 40.6% of compositional variation at family level. Host prediction linked phages to dominant upper-airway colonizers, including Streptococcaceae, Moraxellaceae, Pasteurellaceae, with a marked lifestyle-host polarization: virulent phages were preferentially linked to Bacteroidota (particularly Prevotella), whereas temperate phages were enriched in Streptococcaceae and Moraxellaceae. Integration of viral taxonomy and host affiliation resolved a modular architecture in which a few recurrent phage-host couplings (e.g., Suoliviridae-Bacteroidota, Peduoviridae-Pasteurellaceae, Aliceevansviridae-Streptococcaceae) were conserved but differentially weighted between virulent and temperate fractions. ConclusionsThis study establishes the first phageome catalogue and ecological framework for a respiratory site in livestock. The nasopharyngeal phageome is organized into recurrent, host-linked taxonomic modules jointly constrained by viral lineage, host affiliation and replication strategy, with lifestyle-dependent connections to key colonizers implicated in the porcine respiratory disease complex. This catalogue and its modular architecture provide a foundation for investigating phage-mediated modulation of bacterial dynamics during the post-weaning transition and for the selection of lytic phage candidates targeting respiratory pathogens.

microbiology↗

bioRxiv2024

Biofilm formation in Streptococcus suis: In vitro impact of serovar and assessment of coinfections with other porcine respiratory disease complex bacterial pathogens.

Streptococcus suis is a worldwide pathogen that impacts swine industry, causing severe clinical signs in postweaning piglets, including meningitis and arthritis. Biofilm formation is a major virulence mechanism in S. suis, enhancing its persistence and resistance. Here, we assessed the in vitro biofilm formation of 240 S. suis isolates from Spanish swine farms and evaluated the effects of serovars (SVs) and coinfections with other porcine respiratory disease complex (PRDC) pathogens. Our study revealed significant heterogeneity in biofilm formation among S. suis SVs. Notably, SV2 exhibited the lowest biofilm formation, contrasting with the high biofilm-forming capacities of SV1, SV7, and SV9. Virulence factors epf, mrp, and sly were associated (p < 0.05) with reduced biofilm formation. Other PRDC pathogens, including Actinobacillus pleuropneumoniae, Glaesserella parasuis, and Pasteurella multocida, formed biofilms, though generally less robust than those of S. suis (except for SV2), contrasting the high biofilm formation of Staphylococcus hyicus. Coinfections demonstrated enhanced biofilm formation in mixed cultures of S. suis, particularly with P. multocida. Other coinfections revealed variable results in pathogen interactions, suggesting the potential of biofilms for increased persistence and pathogenicity in coinfections. In conclusion, this study underscores the importance of serovar-specific differences in biofilm formation among S. suis isolates, with significant implications for pathogenicity and persistence. The heterogeneous biofilm formation observed in coinfections with other PRDC pathogens reveals a complex interplay that could exacerbate disease severity. These findings provide a foundation for further research on biofilm mechanisms to mitigate the impact of PRDC in the swine industry.

microbiology↗

bioRxiv2024

Integrated Stress Response Triggered by Excessive Glycosylation Drives Thoracic Aortic aneurysm

Thoracic aortic aneurysms and dissections (TAAD) are marked by degenerative changes in the aortic media. Marfan syndrome is the most common inherited connective tissue disorder associated with TAAD. While vascular smooth muscle cell (VSMC) metabolism is emerging as a targetable driver of aortic aneurysm, surgical interventions remain the primary strategy to prevent aortic dissection. Our research indicates that the hexosamine biosynthetic pathway (HBP), a branch of glycolysis, is upregulated in aortas from the Fbn1C1041G/+ Marfan Syndrome mouse model. Enhancing HBP activity promotes aortic dilation and accumulation glycan-rich extracellular matrix, contributing to aortic medial degeneration in wild-type mice. Mechanistically, fueling HBP activity induces VSMC dysfunction through excessive glycosylation, which activates the Integrated Stress Response (ISR). Pharmacological inhibition of HBP, along with ISR inhibition, successfully reverses aortic dilation and aortic medial degeneration in Fbn1C1041G/+ Marfan Syndrome mouse model. Additionally, Marfan Syndrome patients show elevated levels of HBP metabolites in blood plasma and serum, and heightened HBP-ISR signaling in patients with TAAD. These findings unveil a potential causative role for the HBP-ISR axis in medial degeneration in human TAAD, underscoring the need for evaluating HBP and ISR pathway as novel biomarkers and therapeutic strategies for thoracic aortic aneurysm.

molecular biology↗

bioRxiv2024

TbpB-based oral mucosal vaccine provides heterologous protection against Glasser disease caused by different serovars of Spanish field isolates of Glaesserella parasuis

BackgroundGlaesserella parasuis has a substantial impact on the pig production as the primary agent of Glassers disease, particularly affecting nursery and early fattening stages. Current prophylactic measures, mainly based in serovar-specific bacterins administered parenterally to sows, face limitations due to maternal immunity, which may interfere with the active immunization of piglets. The mucosal administration of TbpB-based subunit vaccines offers a promising approach to overcome these limitations for the control of the disease in weaning piglets. This study evaluates the immunogenicity and heterologous protection of the oral mucosal TbpBY167A subunit vaccine in colostrum-deprived piglets challenged with four G. parasuis clinical isolates belonging to different TbpB clusters and serovars (SVs) recovered from Spanish pig farms. ResultsThe mucosal administration of a two-dose TbpB-based vaccine induced a robust humoral immune response in immunized colostrum-deprived piglets, significantly increasing IgA (p < 0.01) and IgM (p < 0.01) concentration 15 days after the second dose. Subsequent infection challenge with four G. parasuis clinical isolates demonstrated heterologous protection, markedly improving survival rates (OR: 8.45; CI 95%: 4.97-14.36) and significantly reducing clinical signs and lesions, regardless of the G. parasuis TbpB cluster and serovar. The vaccine not only reduced G. parasuis colonization in the respiratory tract of immunized piglets (p < 0.0001), but also in systemic target tissues, such as the tarsus and carpus joints, liver, and brain (p < 0.05). Further immunohistochemical analysis in different lung locations revealed a significantly lower macrophage count in immunized piglets (p < 0.0001). ConclusionsOverall, this study demonstrates that the oral mucosal administration of the TbpBY167A subunits vaccine in piglets provides effective heterologous protection against different virulent European G. parasuis field isolates, significantly reducing bacterial colonization and dissemination. These facts position this TbpB-based vaccine as a leading candidate for a universal vaccine against Glassers disease.

immunology↗

bioRxiv2023

Phosphatase-independent activity of smooth-muscle calcineurin orchestrates a gene expression program leading to hypertension

STRUCTURED ABSTRACTObjective: Angiotensin-II (Ang-II) drives pathological vascular wall remodeling in hypertension and abdominal aortic aneurysm (AAA). Previous studies showed that the phosphatase activity of calcineurin (Cn) mediates Ang-II-induced AAA, but the cell type involved in the action of Cn in AAA formation remained unknown. Methods: Smooth muscle cell (SMC)-specific and endothelial cell (EC)-specific Cn-deficient mice (SM-Cn-/- and EC-Cn-/- mice, respectively) were created and assessed for Ang-II-induced AAA formation and hypertension vs controls. Osmotic minipumps were used to administer Ang-II and cyclosporine A (CsA), a pharmaceutical Cn inhibitor. AAA formation and hypertension were monitored by ultrasonography, arterial blood pressure monitoring, and histological analysis. Deep RNA sequencing was used to identify the Ang-II-regulated transcriptome sensitive to Cn deletion or pharmacological inhibition. Arterial and SMC contractility were also assessed. Results: Cn expressed in SMCs, but not ECs, was required for Ang-II-induced AAA. Unexpectedly, SMC Cn played a structural role in the early onset and maintenance of Ang-II-induced hypertension independently of Cn phosphatase activity. Nearly 90% of the genes regulated by Ang-II in the aorta required Cn expression in SMCs. Cn orchestrated, independently of its enzymatic activity, the induction by Ang-II of a gene expression program closely related to SMC contractility and hypertension. Cn deletion in SMCs, but not its pharmacological inhibition, impaired the regulation of arterial contractility. Among the genes whose regulation by Ang-II required Cn expression but not its phosphatase activity, we discovered that Serpine1 was critical for Ang-II-induced hypertension. Indeed, pharmacological inhibition of PAI-1, the protein encoded by Serpine1, impaired SMCs contractility and readily regressed hypertension. Conclusions: Whereas the phosphatase activity of Cn mediates Ang-II-induced AAA, a phosphatase-independent action of SMC Cn mediates hypertension by orchestrating a gene expression program closely related to contractility and blood pressure regulation. Our results urge the evaluation of PAI-1 as a candidate therapeutic target for hypertension.

pathology↗

bioRxiv2020

miR-203 imposes an intrinsic barrier during cellular reprogramming by targeting NFATC2

Cellular reprogramming from somatic to pluripotent cells is the basis for multiple applications aimed to replace damaged tissues in regenerative medicine. However, this process is limited by intrinsic barriers that are induced in response to reprogramming factors. In this manuscript we report that miR-203, a microRNA with multiple functions in differentiation and tumor suppression, acts as an endogenous barrier to reprogramming. Genetic ablation of miR-203 results in enhanced reprogramming whereas its expression prevents the formation of pluripotent cells both in vitro and in vivo. Mechanistically, this effect correlates with the direct repression of NFATC2, a transcription factor involved in the early phases of reprogramming. Inhibition of NFATC2 mimics miR-203 effects whereas NFATC2 overexpression rescues inducible cell pluripotency in miR-203-overexpressing cultures. These data suggest that miR-203 repression may favor the efficiency of reprogramming in a variety of cellular models.

cell biology↗