Biology subjects

Horcajo, P.

Publications and source records attributed to Horcajo, P..

3 recordsLinked to original sources

bioRxiv2026

Prediction of early Toxoplasma gondii infection during pregnancy combining host biomarkers and machine learning

Toxoplasma gondii is a major cause of reproductive failure and severe gestational complications in both humans and small ruminants and early diagnosis is essential to prevent adverse outcomes. In sheep, congenital toxoplasmosis can trigger early fetal death (EFD) during the acute phase of the infection (days 7-14 post-infection) when conventional diagnosis methods are ineffective. Therefore, this study aimed to identify early infection biomarkers using a machine learning approach to support EFD diagnosis and providing a translational foundation for early diagnostic strategies in human toxoplasmosis. For that, 27 serum biomarkers (cytokines, acute-phase proteins, oxidative stress and hemostatic parameters) were evaluated during the early stage of infection in 22 pregnant sheep experimentally challenged with T. gondii and 6 uninfected controls. To assess diagnostic specificity, models were tested using sera from animals experimentally infected with other abortifacient agents (Neospora caninum and Chlamydia abortus) and validated with samples from 19 natural abortion outbreaks. A four-biomarkers panel, encompassing CXCL9, CXCL10, IFN-{gamma}, and serum amyloid A, achieved over 74% accuracy in the specific detection of early T. gondii infection and 100% of sensitivity when studying natural infection cases. This approach might support the development of rapid diagnostic strategies, improving early intervention and disease management in livestock production systems. Its translation to human medicine could also aid in addressing current diagnostic gaps and facilitate timely interventions to prevent congenital toxoplasmosis and pregnancy loss in women.

immunology↗

bioRxiv2026

Tissue-specific transcriptomic responses to early Toxoplasma gondii infection in sheep during congenital toxoplasmosis

Toxoplasma gondii is a widespread zoonotic pathogen of major One Health concern, capable of causing congenital toxoplasmosis in both humans and sheep. Despite its impact, early host-parasite molecular interactions during acute infection in pregnant hosts remain largely unexplored. In this study, we characterized the transcriptomic responses of key tissues involved in early infection (the small intestine, mesenteric lymph nodes, and placenta) in pregnant ewes experimentally infected with T. gondii strain TgShSp1. RNA-seq analysis revealed pronounced, tissue-specific transcriptional changes at 6 days post-infection (dpi), particularly in the mesenteric lymph nodes, characterized by activation of interferon- and cytokine-mediated immune pathways. In contrast, transcriptional responses at 3 dpi were limited, consistent with a silent phase of parasite dissemination. Despite the absence of detectable parasite DNA, placentomes showed modest interferon-associated responses and upregulation of DNA repair and cellular stress pathways. These changes coincided with marked suppression of cell-cycle progression and extracellular matrix remodeling alongside inhibition of angiogenesis and hypoxia pathways. Altogether, early disruption of placental vascular function and tissue remodeling may contribute to fetal loss. In summary, these findings provide new insights into early host responses to T. gondii infection in a pregnant host and identify molecular mechanisms that may predispose to early fetal death during ovine congenital toxoplasmosis.

microbiology↗

bioRxiv2020

Massive genome decay and expansion of insertion sequences drive the evolution of a novel host-restricted bacterial pathogen

BackgroundThe emergence of new pathogens is a major threat to public and veterinary health. Changes in bacterial habitat such as those associated with a switch in host or disease tropism are often accompanied by genetic adaptation. Staphylococcus aureus is a multi-host bacterial species comprising strains with distinct tropisms for human and livestock species. A microaerophilic subspecies, Staphylococcus aureus subsp. anaerobius, is responsible for outbreaks of Morels disease, a lymphadenitis in small ruminants. However, the evolutionary history of S. aureus subsp. anaerobius and its relatedness to S. aureus are unknown. ResultsEvolutionary genomic analyses of clinical S. aureus subsp. anaerobius isolates revealed a highly conserved clone that descended from a S. aureus progenitor about 1000 years ago before differentiating into distinct lineages representing African and European isolates. S. aureus subsp. anaerobius has undergone limited clonal expansion, with a restricted population size, and an evolutionary rate 10-fold slower than S. aureus. The transition to its current restricted ecological niche involved acquisition of a pathogenicity island encoding a ruminant host-specific effector of abscess formation, several large chromosomal re-arrangements, and the accumulation of at least 205 pseudogenes resulting in a highly fastidious metabolism. Importantly, expansion of [~]87 insertion sequences (IS) located largely in intergenic regions provided distinct mechanisms for the control of expression of flanking genes, representing a novel concept of the IS regulon. ConclusionsOur findings reveal the remarkable evolutionary trajectory of a host-restricted bacterial pathogen that resulted from extensive remodelling of the S. aureus genome through an array of parallel mechanisms.

microbiology↗