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Title

Trypanosoma brucei gambiense Adaptation to Different Mammalian Sera Is Associated with VSG Expression Site Plasticity

AuthorsCordon-Obras, Carlos; Cano, Jorge; Gongález-Pacanowska, D.; Benito, Agustín; Navarro Carretero, Miguel Ángel; Bart, Jean-Mathieu
Issue Date23-Dec-2013
PublisherPublic Library of Science
AbstractTrypanosoma brucei gambiense infection is widely considered an anthroponosis, although it has also been found in wild and domestic animals. Thus, fauna could act as reservoir, constraining the elimination of the parasite in hypo-endemic foci. To better understand the possible maintenance of T. b. gambiense in local fauna and investigate the molecular mechanisms underlying adaptation, we generated adapted cells lines (ACLs) by in vitro culture of the parasites in different mammalian sera. Using specific antibodies against the Variant Surface Glycoproteins (VSGs) we found that serum ACLs exhibited different VSG variants when maintained in pig, goat or human sera. Although newly detected VSGs were independent of the sera used, the consistent appearance of different VSGs suggested remodelling of the co-transcribed genes at the telomeric Expression Site (VSG-ES). Thus, Expression Site Associated Genes (ESAGs) sequences were analysed to investigate possible polymorphism selection. ESAGs 6 and 7 genotypes, encoding the transferrin receptor (TfR), expressed in different ACLs were characterised. In addition, we quantified the ESAG6/7 mRNA levels and analysed transferrin (Tf) uptake. Interestingly, the best growth occurred in pig and human serum ACLs, which consistently exhibited a predominant ESAG7 genotype and higher Tf uptake than those obtained in calf and goat sera. We also detected an apparent selection of specific ESAG3 genotypes in the pig and human serum ACLs, suggesting that other ESAGs could be involved in the host adaptation processes. Altogether, these results suggest a model whereby VSG-ES remodelling allows the parasite to express a specific set of ESAGs to provide selective advantages in different hosts. Finally, pig serum ACLs display phenotypic adaptation parameters closely related to human serum ACLs but distinct to parasites grown in calf and goat sera. These results suggest a better suitability of swine to maintain T. b. gambiense infection supporting previous epidemiological results. Figures 12 Citation: Cordon-Obras C, Cano J, González-Pacanowska D, Benito A, Navarro M, et al. (2013) Trypanosoma brucei gambiense Adaptation to Different Mammalian Sera Is Associated with VSG Expression Site Plasticity. PLoS ONE 8(12): e85072. doi:10.1371/journal.pone.0085072 Editor: Mauricio Martins Rodrigues, Federal University of São Paulo, Brazil Received: July 31, 2013; Accepted: November 21, 2013; Published: December 23, 2013 Copyright: © 2013 Cordon-Obras et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by grants from the Spanish Ministerio de Ciencia e Innovación, Plan Nacional (SAF2012-40029), Junta de Andalucia (CTS-5841), Fondo de Investigación Sanitaria (FIS) PI10/01128 and VI PN de I+D+I 2008-2011, ISCIII -Subdirección General de Redes y Centros de Investigación Cooperativa (RICET) RD12/0018/0001 and RD12/0018/0015. JMB is supported by a Miguel Servet Fellowship CP09/00300. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist.
Publisher version (URL)http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0085072#ack
URIhttp://hdl.handle.net/10261/93122
DOI10.1371/journal.pone.0085072
ISSN1932-6203
Appears in Collections:(IPBLN) Artículos
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