Leptospira is a bacterial genus that includes several pathogenic species related to leptospirosis. In Colombia, leptospirosis is a mandatorily reported disease, widely distributed across the country. In the Villeta municipality, leptospirosis has been identified as an important cause of febrile illness; however, to date, no studies have been performed to identify the circulating species. A genus-specific qualitative qPCR was performed on DNA extracted from febrile patients’ acute-phase whole-blood samples targeting a fragment of the rrs gene. Positive qPCR samples were further amplified for the adk, icdA, LipL32, LipL41, rrs, and secY genes through conventional PCR for sequencing. All high-quality obtained sequences were further assessed through concatenated phylogenetic analysis. A total of 25% (14/56) of febrile patients’ acute blood samples were positive for Leptospira spp. High-quality sequences were obtained for only five genes, and analysis through concatenated phylogeny identified that all sequences clustered within the P1/pathogenic clade; some of them formed a robustly supported clade with Leptospira santarosai, and others were closely related with other Leptospira species but exhibited considerable genetic divergence. We describe the presence of pathogenic Leptospira species among febrile patients from the Villeta municipality and identify L. santarosai and other Leptospira species as causative agents of leptospirosis in the region.

Astrocytes play a pivotal role in maintaining brain homeostasis. Recent research has highlighted the significance of palmitic acid (PA) in triggering pro-inflammatory pathways contributing to neurotoxicity. Furthermore, Genomic-scale metabolic models and control theory have revealed that metabolic switches (MSs) are metabolic pathway regulators by potentially exacerbating neurotoxicity, thereby offering promising therapeutic targets. Herein, we characterized these enzymatic MSs in silico as potential therapeutic targets, employing protein–protein and drug–protein interaction networks alongside structural characterization techniques. Our findings indicate that five MSs (P00558, P04406, Q08426, P09110, and O76062) were functionally linked to nervous system drug targets and may be indirectly regulated by specific neurological drugs, some of which exhibit polypharmacological potential (e.g., Trifluperidol, Trifluoperazine, Disulfiram, and Haloperidol). Furthermore, four MSs (P00558, P04406, Q08426, and P09110) feature ligand-binding or allosteric cavities with druggable potential. Our results advocate for a focused exploration of P00558 (phosphoglycerate kinase 1), P04406 (glyceraldehyde-3-phosphate dehydrogenase), Q08426 (peroxisomal bifunctional enzyme, enoyl-CoA hydratase, and 3-hydroxyacyl CoA dehydrogenase), P09110 (peroxisomal 3-ketoacyl-CoA thiolase), and O76062 (Delta(14)-sterol reductase) as promising targets for the development or repurposing of pharmacological compounds, which could have the potential to modulate lipotoxic-altered metabolic pathways, offering new avenues for the treatment of related human diseases such as neurological diseases.

Zika virus (ZIKV) is a neurotropic flavivirus linked to severe neurodevelopmental defects following prenatal exposure. While the mechanisms by which ZIKV spreads within the central nervous system remain incompletely understood, extracellular vesicles (EVs) have emerged as potential mediators of intercellular communication and viral dissemination. Here, we demonstrate that EVs derived from ZIKV-infected neural cells encapsulate full-length viral genomes capable of establishing productive in vivo infection, independent of free virions. Primary cortical neurons, astrocytes, and mouse brain microvascular endothelial cells (MBECs) from neonatal mice were infected with ZIKV at a low multiplicity of infection (MOI 0.1). EVs were isolated and treated with acid glycine buffer and RNAase to exclude residual virions or free RNA. RNA sequencing, RT-qPCR, and droplet digital PCR (dd-PCR) analyses revealed that EVs—particularly those derived from neurons and MBECs—encapsulated ZIKV RNA, including full-length viral genomes. These EVs were able to transfer viral RNA to A549 cells in vitro , and its intracranial injection into neonatal mice resulted in productive infection, confirmed by detection of ZIKV capsid protein, viral RNA, and viral antigen in brain tissue. Our findings demonstrate that EVs from ZIKV-infected neural cells can serve as vehicles for genome transfer and initiate infection, even in the absence of detectable virions. The persistence of EVs-packaged genomes post-viremia could explain clinical observations of prolonged ZIKV RNA within the nervous tissue or delayed transmission. Understanding this pathway provides new insights into ZIKV neuropathogenesis and opens potential avenues for therapeutic intervention, for example targeting EVs biogenesis or cargo sorting.