Biology subjects

Cupolillo, E.

Publications and source records attributed to Cupolillo, E..

6 recordsLinked to original sources

bioRxiv2025

Genomic evidence for co-evolution and sporadic host shifts in leishmaniaviruses

The association between Leishmania parasites and the double-stranded RNA virus, Leishmaniavirus (LRV), significantly impacts human health by modulating disease severity. Despite its clinical importance, the evolutionary history of this symbiosis remains largely unknown. This study presents one of the first formal investigations of their co-phylogenetic history across different taxonomic hierarchical levels; based on total RNA sequencing of cultivated isolates, simultaneously capturing the parasite`s transcriptome and the viral genome. We found strong support for phylogenetic congruence between Leishmania and LRV at both the subgenus and species level; based on genetic distance correlations and formal co-phylogenetic statistics. Focusing on the interactions of L. (V.) braziliensis and L. (V.) guyanensis with LRV1, we observed weaker co-phylogenetic signals though frequent instances of intraspecific host switching. Together, our findings indicate that LRV has been a persistent evolutionary partner of Leishmania, providing a framework for understanding the emergence and maintenance of virus-mediated disease phenotypes.

evolutionary biology↗

bioRxiv2025

Tracking the Spread of a Naturally Occurring Leishmania infantumMutant: A qPCR-Based Investigation in Strains and Clinical Samples

The circulation of Leishmania infantum strains carrying a 12 Kb genomic deletion (DEL) alongside wild-type (NonDEL) parasites in the Americas raises critical epidemiological questions. To support molecular surveillance efforts, we developed and validated a qPCR-based genotyping tool capable of detecting and quantifying DEL, NonDEL, and coinfection (MIX) profiles. The strategy targets a constitutive region present in all strains and a specific region exclusive to NonDEL parasites. It was validated using DNA from cultured parasites and applied to a panel of diverse clinical samples from dogs, humans, and other hosts across South and Central America. DEL genotypes were found to be more frequent and widespread, both in clinical samples and cultured parasites, suggesting their significant role in the transmission cycle. The tools application revealed coinfections in paired samples and enabled relative quantification of genotypes. It also showed good correlation with parasite load estimations and high discriminatory power when integrated with the Genotype function of real-time PCR software. This protocol provides a robust, scalable approach for monitoring L. infantum genotypes, with direct implications for understanding infection dynamics, treatment outcomes and public health surveillance. Author SummaryLeishmania infantum is the parasite responsible for visceral leishmaniasis in the Americas. Recent studies have shown that two distinct genotypes--those carrying a specific gene deletion (DEL) and those without it (NonDEL)--coexist and circulate in the region. Understanding how these genotypes are distributed and whether they affect disease transmission or treatment is critical, especially because Miltefosine, a drug used to treat dogs, may not work equally well against both genotypes. In this study, we developed a simple and accurate molecular test to detect and quantify these genotypes in both cultured parasites and clinical samples from different animal hosts, including humans. We found that DEL genotypes are common and widely distributed, and that some animals carry both types of parasites simultaneously. Our method also distinguishes L. infantum from other related species, making it useful for diagnosis and surveillance. This tool can help researchers and health authorities monitor parasite populations more effectively and better understand how different genotypes might impact disease outcomes and control strategies.

microbiology↗

bioRxiv2024

The global dispersal of visceral leishmaniasis occurred within human history

The Leishmania donovani species complex (LdSC) causes visceral leishmaniasis (VL), is present in Africa, Europe, the Middle East, Asia and the Americas, and causes 20-40,000 fatalities per year. Previous analyses concluded that dispersal of this species complex occurred 1-10 million years ago. Using updated methods and data, we show that a ten-thousand year old East African population dispersed globally only within the last 2,000 years, consistent with human migration, war and colonisation as driving factors.

evolutionary biology↗

bioRxiv2024

Evolutionary genomics of a zoonotic parasite across the Neotropical Realm

The Neotropical realm, one of the most biodiverse regions on Earth, houses a broad range of zoonoses that pose serious public health threats. Protozoan parasites of the Leishmania (Viannia) braziliensis species complex cause zoonotic leishmaniasis in Latin America with clinical symptoms ranging from simple cutaneous to destructive, disfiguring mucosal lesions. We present the first comprehensive genome-wide continental study including 257 cultivated isolates representing most of the geographical distribution of this major human pathogen. The L. braziliensis species complex is genetically highly heterogeneous, consisting of divergent parasite groups that are associated with different environments and vary greatly in diversity. Apart from several small ecologically isolated groups with little diversity, our sampling identifies two major parasite groups, one associated with the Amazon and the other with the Atlantic Forest biomes. These groups show different recombination histories, as suggested by high levels of heterozygosity and effective population sizes in the Amazonian group in contrast to high levels of linkage and clonality in the Atlantic group. We argue that these differences are linked to strong eco-epidemiological differences between the two regions. In contrast to geographically focused studies, our study provides a broad understanding of the molecular epidemiology of zoonotic parasites circulating in tropical America.

evolutionary biology↗

bioRxiv2024

Gene deletion as a possible strategy adopted by New World Leishmania infantum to maximize geographic dispersion

BackgroundThe present study investigates implications of a sub-chromosomal deletion in Leishmania infantum strains, the causative agent of American Visceral Leishmaniasis (AVL). Primarily found in New World strains, the deletion leads to the absence of the ecto-3-nucleotidase/nuclease enzyme (3NU/NT), impacting parasite virulence, pathogenicity, and drug susceptibility. The potential factors favoring prevalence and the widespread geographic distribution of these deleted mutant parasites (DEL) in the New World (NW) are discussed under the generated data. MethodsWe conducted phenotypic analyses of the parasites showing the sub- chromosomal deletion by applying in vitro assays of 3NU/NT activity, metacyclic enrichment, and relative quantitation of transcripts abundance on axenic parasites. We further performed experimental infections in both in vitro and in vivo models of vertebrate and invertebrate hosts using geographically diverse mutant field isolates. ResultsVirulence assays, poorer ability to survive neutrophil traps (NETs) and murine model infection revealed reduced pathogenicity in vertebrate hosts by the DEL strains. Conversely, these parasites exhibit enhanced metacyclogenesis and colonization rates in sand flies, potentially facilitating transmission. This combination may represent a more efficient way to maintain and disperse the transmission cycle of DEL strains. ConclusionsPhenotypic assessments reveal altered parasite fitness, with enhanced transmissibility at the population level. Reduced susceptibility of DEL strains to miltefosine, a key drug in VL treatment, further complicates control efforts. Our study underscores the importance of typing parasite genomes for surveillance and control and proposes the sub-chromosomal deletion as a molecular marker in AVL management.

microbiology↗

bioRxiv2019

Ecological divergence and hybridization of Neotropical Leishmania parasites

The tropical Andes is an important natural laboratory to understand speciation and diversification in many taxa. Here, we examined the evolutionary history of parasites of the Leishmania braziliensis species complex based on whole genome sequencing of 67 isolates from 47 localities in Peru. We firstly show the origin of near-clonal Andean Leishmania lineages that diverged from admixed Amazonian ancestors, accompanied by a significant reduction in genome diversity and large structural variations implicated in host-parasite interactions. Beside a clear dichotomy between Andean and Amazonian species, patterns of population structure were strongly associated with biogeographical origin. Molecular clock analyses and ecological niche modeling suggested that the history of diversification of the Andean lineages is limited to the Late Pleistocene and intimately associated with habitat contractions driven by climate change. These results support a wider model on trypanosomatid evolution where major parasite lineages emerge through ecological fitting. Second, genome-scale analyses provided evidence of meiotic recombination between Andean and Amazonian Leishmania species, resulting in full-genome hybrids. The mitochondrial genome of these hybrids consisted of homogeneous uniparental maxicircles, but minicircles originated from both parental species, leaving a mosaic ancestry of minicircle-encoded guide RNA genes. We further show that mitochondrial minicircles - but not maxicircles - show a similar evolutionary pattern as the nuclear genome, suggesting that biparental inheritance of minicircles is universal and may be important to alleviate maxicircle-nuclear incompatibilities. By comparing full nuclear and mitochondrial genome ancestries, our data expands our appreciation on the genetic consequences of diversification and hybridization in parasitic protozoa.

genomics↗