Biology subjects

Gonzalez-Fernandez, A.

Publications and source records attributed to Gonzalez-Fernandez, A..

4 recordsLinked to original sources

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

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

Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target

With colorectal cancer (CRC) being the second most common cause of cancer-related deaths worldwide1, there is an urgent need for better diagnostic tools and new, more targeted therapies. Here we used genetically engineered mouse models (GEMMs), and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that unsupervised metabolic profiling can stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging (MSI) to identify tumour, stromal and normal adjacent tissues. By identifying ions that drive variation between normal and transformed tissues, we found dysregulation of the methionine cycle to be a hallmark of APC-mutant CRC, and propose one of its enzymes, i.e. adenosylhomocysteinase (AHCY), as a new therapeutic target. Collectively, we show that the profound genotype-dependent alterations in both lipid and small molecule metabolism in CRC may be exploited for tissue classification with no need for ion identification, and we applied further data analysis to expose a novel metabolic vulnerability of CRC.

cancer biology↗

bioRxiv2022

Bordetella spp. block eosinophil recruitment to suppress lung iBALT formation

A characteristic that differentiates pathogenic and opportunistic bacteria is that pathogens have been selected by their ability to suppress host inflammatory responses allowing colonization and persistence. Bordetella spp. are respiratory pathogens characterized for the arsenal of mechanisms they use to manipulate host immune responses. We have previously characterized a B. bronchiseptica mutant, RB50{Delta}btrS, that is not able to suppress host immune responses, resulting not only in rapid clearance of the infection but also long-term lung sterilizing immunity against reinfection with the three classical Bordetella spp. Interestingly, this strong immune response requires eosinophils. In this work our results indicate that wildtype B. bronchiseptica, RB50, blocks eosinophil pro-inflammatory functions to prevent the rapid recruitment of B and T cells to the lung that results in iBALT formation. Moreover, eosinophils promote a TH17 microenvironment within the iBALT that might be responsible for the long-term robust protective immunity generated by infection with this mutant. Overall, this work provides a novel role for eosinophils as promoters of adaptive immune responses and protective immunity, while also indicating that bacteria actively manipulate those cells to promote long-term persistence and reinfection.

microbiology↗