Search bioRxiv⌕ Search

Biology subjects

Montero, E.

Publications and source records attributed to Montero, E..

3 recordsLinked to original sources

Comparative analysis of the EF-1α Intergenic Region in Babesia divergens isolates: Insights into TA Repeat Variation and Potential Regulatory Implications

Babesia divergens, a zoonotic tick-borne pathogen, causes bovine and human babesiosis in Europe. The Elongation Factor 1 alpha (EF-1) protein is important in many cellular processes and has emerged as a possible target for subunit vaccine development against parasitic infections, and its intergenic region (IG) is an important tool for genetic manipulation of Babesia parasites. While the EF-1 locus of B. divergens has been described, structural variation between isolates was poorly defined. In order to fill this gap, we performed a comparative analysis of the EF-1-IG region in B. divergens human (Rouen 87, and Spanish sample), and bovine (Turkiye) host isolates. Our findings revealed both conserved and variable elements, particularly in TA nucleotide repeat numbers and IG sequence length. The Spanish isolate exhibited the highest TA repeat expansion, whereas the Rouen 87 strain had the shortest IG region. Given the known role of repeat-rich promoter elements in gene regulation, these differences may influence EF-1 transcription. Additionally, these findings provide insights into the evolutionary divergence of B. divergens and its host adaptation mechanisms. This study establishes a foundation for future gene editing and transfection strategies, where selecting intergenic sequences with varying TA repeats could optimize transfection efficiency and explain phenotypic differences between isolates from different hosts or regions.

genomics↗

Multiomics analysis reveals B. MO1 as a distinct Babesia species and provides insights into its evolution and virulence.

Babesiosis, caused by protozoan parasites of the genus Babesia, is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of various Babesia species underscores the ongoing risk of new zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental shifts impacting the distribution and transmission dynamics of parasites, their vectors, and reservoir hosts. One such species, Babesia MO1, previously implicated in severe cases of human babesiosis in the midwestern United States, was initially considered closely related to B. divergens, the predominant agent of human babesiosis in Europe. Yet, uncertainties persist regarding whether these pathogens represent distinct variants of the same species or are entirely separate species. We show that although both B. MO1 and B. divergens share similar genome sizes, comprising three nuclear chromosomes, one linear mitochondrial chromosome, and one circular apicoplast chromosome, major differences exist in terms of genomic sequence divergence, gene functions, transcription profiles, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens, and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.

microbiology↗

Four-dimensional characterization of the Babesia divergens asexual life cycle: from the trophozoite to the multiparasite stage

Babesia is an apicomplexan parasite of significance that causes the disease known as babesiosis in domestic and wild animals and in humans worldwide. Babesia infects vertebrate hosts and reproduces asexually by a form of binary fission within erythrocytes/red blood cells (RBCs), yielding a complex pleomorphic population of intraerythrocytic parasites. Seven of them, clearly visible in human RBCs infected with Babesia divergens, are considered the main forms and named single, double and quadruple trophozoites, paired and double paired-pyriforms, tetrad or Maltese Cross, and multiparasite stage. However, these main intraerythrocytic forms coexist with RBCs infected with transient parasite combinations of unclear origin and development. In fact, little is understood about how Babesia builds this complex population during its asexual life cycle. By combining the emerging technique cryo soft X-ray tomography and video microscopy, main and transitory parasites were characterized in a native whole cellular context and at nanometric resolution. As a result, the architecture and kinetic of the parasite population has been elucidated. Importantly, the process of multiplication by binary fission, involving budding, was visualized in live parasites for the first time, revealing that fundamental changes in cell shape and continuous rounds of multiplication occur as the parasites go through their asexual multiplication cycle. Based on these observations, a four-dimensional (4D) asexual life cycle model has been designed highlighting the origin of the tetrad, double paired-pyriform and multiparasite stages and the transient morphological forms that, surprisingly, intersperse in a chronological order between one main stage and the next along the cycle. IMPORTANCEBabesiosis is a disease caused by intraerythrocytic Babesia parasites, which possess many clinical features that are similar to those of malaria. This worldwide disease, is increasing in frequency and geographical range, and has a significant impact on human and animal health. Babesia divergens is one of the species responsible for human and cattle babesiosis causing death unless treated promptly. When B. divergens infects its vertebrate hosts it reproduces asexually within red blood cells. During its asexual life cycle, B. divergens builds a population of numerous intraerythrocytic (IE) parasites of difficult interpretation. This complex population is largely unexplored, and we have therefore combined three and four dimensional (3D and 4D) imaging techniques to elucidate the origin, architecture, and kinetic of IE parasites. Unveil the nature of these parasites have provided a vision of the B. divergens asexual cycle in unprecedented detail and a key step to develop control strategies against babesiosis

microbiology↗