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dc.contributor.authorConesa, José Javier
dc.contributor.authorSevilla, Elena 
dc.contributor.authorTerrón-Orellana, Maria Carmen 
dc.contributor.authorGonzalez, Luis Miguel 
dc.contributor.authorGray, Jeremy
dc.contributor.authorPérez-Berná, Ana J
dc.contributor.authorCarrascosa, José L
dc.contributor.authorPereiro, Eva
dc.contributor.authorChichón, Francisco Javier
dc.contributor.authorLuque, Daniel 
dc.contributor.authorMontero-Clemente, Estrella
dc.identifier.citationmSphere . 2020 Oct 14;5(5):e00928-20.es_ES
dc.description.abstractBabesia 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 cryo-soft X-ray tomography and video microscopy, main and transitory parasites were characterized in a native whole cellular context and at nanometric resolution. The architecture and kinetics of the parasite population was observed in detail and provide additional data to the previous B. divergens asexual life cycle model that was built on light microscopy. 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. A four-dimensional asexual life cycle model was built highlighting the origin of several transient morphological forms that, surprisingly, intersperse in a chronological order between one main stage and the next in the cycle.IMPORTANCE Babesiosis 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 imaging techniques to elucidate the origin, architecture, and kinetics of IE parasites. Unveiling the nature of these parasites has provided a vision of the B. divergens asexual cycle in unprecedented detail and is a key step to develop control strategies against babesiosis.es_ES
dc.description.sponsorshipThis study was funded by grants from Ministerio de Economía y Competitividad from Spain (AGL2010-21774, AGL2014-56193-R to E.M. and L.M.G., and BFU2013-43149-R to D.L.). Cryo-SXT experiments were funded by ALBA synchrotron from Barcelona, Spain (proposals 2016021614 and 2017022084) and performed at MISTRAL beamline at ALBA Synchrotron with the collaboration of ALBA staff. E.S. was awarded a research fellowship from Plan Estatal de Investigación Científica y Técnica y de Innovación.es_ES
dc.publisherAmerican Society for Microbiology (ASM) es_ES
dc.subjectBabesia divergenses_ES
dc.subjectCryo-soft X-ray tomographyes_ES
dc.subjectIntraerythrocytic asexual cyclees_ES
dc.subjectPathogen-host cell interactionses_ES
dc.subjectTime-lapse video microscopyes_ES
dc.titleFour-Dimensional Characterization of the Babesia divergens Asexual Life Cycle, from the Trophozoite to the Multiparasite Stage.es_ES
dc.typeresearch articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiología::Unidades Comunes Científico-Técnicas (UCCT)
dc.rights.accessRightsopen accesses_ES

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