Multiple hybrid genotypes of Leishmania (viannia) in a focus of mucocutaneous Leishmaniasis.

Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
The American journal of tropical medicine and hygiene (Impact Factor: 2.53). 04/2007; 76(3):573-8.
Source: PubMed

ABSTRACT The principal agent of mucocutaneous leishmaniasis (MCL) is the South American protozoan parasite Leishmania (Viannia) braziliensis. This organism is generally considered to be clonal, that is, it does not to undergo genetic exchange. Nevertheless, apparent hybrids between several Leishmania species have been reported in the New World and the Old World. When we characterized isolates of Leishmania (Viannia) from a single focus of cutaneous leishmaniasis (CL) and MCL, we found a remarkable phenotypic and genotypic diversity, with 12 zymodemes and 20 microsatellite genotypes. Furthermore, 26 of the 59 isolates were L. braziliensis/L. peruviana phenotypic hybrids that displayed 7 different microsatellite genotypes. A hybrid genotype was the only organism isolated from 4 patients with MCL. Thus hybrids must be included among the potential agents of MCL. Despite the propensity for clonality, hybrids are also an important feature of Leishmania (Viannia) and may give rise to epidemiologically important emergent genotypes.

0 0
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Although asexual reproduction via clonal propagation has been proposed as the principal reproductive mechanism across parasitic protozoa of the Leishmania genus, sexual recombination has long been suspected, based on hybrid marker profiles detected in field isolates from different geographical locations. The recent experimental demonstration of a sexual cycle in Leishmania within sand flies has confirmed the occurrence of hybridisation, but knowledge of the parasite life cycle in the wild still remains limited. Here, we use whole genome sequencing to investigate the frequency of sexual reproduction in Leishmania, by sequencing the genomes of 11 Leishmania infantum isolates from sand flies and 1 patient isolate in a focus of cutaneous leishmaniasis in the Çukurova province of southeast Turkey. This is the first genome-wide examination of a vector-isolated population of Leishmania parasites. A genome-wide pattern of patchy heterozygosity and SNP density was observed both within individual strains and across the whole group. Comparisons with other Leishmania donovani complex genome sequences suggest that these isolates are derived from a single cross of two diverse strains with subsequent recombination within the population. This interpretation is supported by a statistical model of the genomic variability for each strain compared to the L. infantum reference genome strain as well as genome-wide scans for recombination within the population. Further analysis of these heterozygous blocks indicates that the two parents were phylogenetically distinct. Patterns of linkage disequilibrium indicate that this population reproduced primarily clonally following the original hybridisation event, but that some recombination also occurred. This observation allowed us to estimate the relative rates of sexual and asexual reproduction within this population, to our knowledge the first quantitative estimate of these events during the Leishmania life cycle.
    PLoS Genetics 01/2014; 10(1):e1004092. · 8.52 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Chagas disease is a systemic pathology caused by Trypanosoma cruzi. This parasite reveals remarkable genetic variability, evinced in six Discrete Typing Units (DTUs) named from T. cruzi I to T. cruzi VI (TcI to TcVI). Recently newly identified genotypes have emerged such as TcBat in Brazil, Colombia and Panama associated to anthropogenic bats. The genotype with the broadest geographical distribution is TcI, which has recently been associated to severe cardiomyopathies in Argentina and Colombia. Therefore, new studies unraveling the genetic structure and natural history of this DTU must be pursued. We conducted a spatial and temporal analysis on 50 biological clones of T. cruzi I (TcI) isolated from humans with different clinical phenotypes, triatomine bugs and mammal reservoirs across three endemic regions for Chagas disease in Colombia. These clones were submitted to a nuclear Multilocus Sequence Typing (nMLST) analysis in order to elucidate its genetic diversity and clustering. After analyzing 13 nuclear housekeeping genes and obtaining a 5821 bp length alignment, we detected two robust genotypes within TcI henceforth named TcIDOM (associated to human infections) and a second cluster associated to peridomestic and sylvatic populations. Additionaly, we detected putative events of recombination and an intriguing lack of linkage disequilibrium. These findings reinforce the emergence of an enigmatic domestic T. cruzi genotype (TcIDOM), and demonstrates the high frequency of recombination at nuclear level across natural populations of T. cruzi. Therefore, the need to pursue studies focused on the diferential virulence profiles of TcI strains. The biological and epidemiological implications of these findings are herein discussed.
    BMC Genetics 09/2013; 14(1):96. · 2.81 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Visceral leishmaniasis (VL), a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum), is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT), has high sensitivity and specificity in South Asia but is less sensitive in East Africa. One of the underlying reasons may be continent-specific molecular diversity in the rK39 antigen within the L. donovani complex. However, a second reason may be differences in specific IgG anti-Leishmania levels in patients from different geographical regions, either due to variable antigenicity or immunological response. We determined IgG titres of Indian and Sudanese VL patients against whole cell lysates of Indian and Sudanese L. donovani strains. Indian VL patients had significantly higher IgG titres against both L. donovani strains compared to Sudanese VL patients (p<0.0001). Mean reciprocal log10 50% end-point titres (1/log10t50) were i) 3.80 and 3.88 for Indian plasma and ii) 2.13 and 2.09 for Sudanese plasma against Indian and Sudanese antigen respectively (p<0.0001). Overall, the Indian VL patients therefore showed a 46.8-61.7 -fold higher mean ELISA titre than the Sudanese VL patients. The higher IgG titres occurred in children (<16 years old) and adults of either sex from India (mean 1/log10t50: 3.60-4.15) versus Sudan (mean 1/log10t50: 1.88-2.54). The greatest difference in IgG responses was between male Indian and Sudanese VL patients of ≥ 16 years old (mean 1/log10t50: 4.15 versus 1.99 = 144-fold (p<0.0001). Anti-Leishmania IgG responses among VL patients in Sudan were significantly lower than in India; this may be due to chronic malnutrition with Zn(2+) deficiency, or variable antigenicity and capacity to generate IgG responses to Leishmania antigens. Such differential anti-Leishmania IgG levels may contribute to lower sensitivity of the rK39-ICT in East Africa.
    PLoS Neglected Tropical Diseases 02/2014; 8(2):e2675. · 4.57 Impact Factor


Available from