Evidence that interspecies <i>Leishmania</i> hybrids contribute to changes in disease pathology
Notice bibliographique
Résumé
Abstract Background Leishmaniasis is a widespread neglected tropical disease present in over 90 countries with diverse pathologies associated with different species of Leishmania parasites transmitted by infected sand flies. Leishmania donovani causes visceral leishmaniasis, a highly virulent fatal infection of the visceral organs. Leishmania major and Leishmania tropica cause less virulent cutaneous leishmaniasis where the infection remains in the skin at the site of the sandfly bite. A major molecular epidemiological question is why some variants of L. donovani in Sri Lanka cause cutaneous disease rather than the typical visceral disease. Methods Whole genome sequencing data for 684 L. donovani samples was used to perform sequence alignments and worldwide phylogenetic analyses to determine the source of the atypical L. donovani strains from Sri Lanka. L. donovani genome sequences originating from Sri Lanka were further analyzed for evidence of hybridization with other Leishmania species by determining the density of heterozygous alleles. Polymorphisms from potential Leishmania hybrids were used to reconstruct the parental genetic sequences to identify the potential parental species and quantify their genetic contribution through sequence comparison of the reconstructed parental sequences with all Old World Leishmania genomes. Findings Here we show that L. donovani in Sri Lanka contains genes with widespread gene polymorphisms derived from African L. major and L. tropica genomes that were likely obtained as a result of diploid genome hybridization and recombination resulting in progeny with mosaic genomes. Furthermore, evidence is presented that multiple L. donovani hybrid parasites originating from visceral leishmaniasis endemic Africa have entered Sri Lanka yet visceral leishmaniasis remains non-existent raising the possibility that environmental factors favour the establishment of atypical L. donovani strains in Sri Lanka. Interpretation The discovery of L. major and L. tropica genome sequences in L. donovani provides a compelling rationale how some L. donovani strains in Sri Lanka may be able to cause cutaneous rather than visceral leishmaniasis. The identification of L. donovani hybrid parasites in cutaneous leishmaniasis lesions provides a unique opportunity to investigate environmental and parasite genetic factors controlling disease epidemiology and pathogenesis. Funding Canadian Institutes of Health Research and Fonds de recherche du Québec – Santé Research in context Evidence before this study Different Leishmania species parasites cause either benign cutaneous leishmaniasis or fatal visceral leishmaniasis. It is unknown why some variants of Leishmania donovani that typically causes visceral leishmaniasis in Asia and Africa can cause cutaneous leishmaniasis in specific geographic locations including Sri Lanka. Leishmania has a diploid genome and hybrid parasites have been identified in nature and generated experimentally. In the context of this study, hybrids are considered to be progeny derived from a single outcross event between two diverse parents. Uncertainty remains whether interspecies hybrids with visceral and cutaneous leishmaniasis causing species in nature are associated with different disease outcomes. Added value of this study Evidence for genetic hybridization between visceral and cutaneous disease causing Leishmania species is described from Sri Lanka where cutaneous leishmaniasis is highly endemic yet there is no ongoing visceral leishmaniasis transmission. This provides a potential explanation how L. donovani can become attenuated for visceral disease and could help to identify geographic environmental factors associated with selection for parasite attenuation. Implications of all the available evidence Hybrid Leishmania parasites may be one source of atypical cutaneous leishmaniasis. Epidemiological studies are needed to determine why diverse L. donovani hybrid parasites have become ubiquitous in specific geographic locations where the incidence of cutaneous leishmaniasis is increasing. This has implications for understanding the genetic control of disease pathogenesis and for the prevention of cutaneous or visceral leishmaniasis locally and in neighboring countries.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».