Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 30, Number 9—September 2024
Research

Autochthonous Leishmaniasis Caused by Leishmania tropica, Identified by Using Whole-Genome Sequencing, Sri Lanka

Hermali Silva1, Tiago R. Ferreira1, Kajan Muneeswaran, Sumudu R. Samarasinghe, Eliza V.C. Alves-Ferreira, Michael E. Grigg, Naduviladath V. Chandrasekharan, David L. Sacks, and Nadira D. KarunaweeraComments to Author 
Author affiliations: University of Colombo, Colombo, Sri Lanka (H. Silva, K. Muneeswaran, S.R. Samarasinghe, N.V. Chandrasekharan, N.D. Karunaweera); Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland, USA (T.R. Ferreira, E.V.C. Alves-Ferreira, M.E. Grigg, D.L. Sacks)

Main Article

Figure 5

Phylogenetic network of all Leishmania isolates from Sri Lanka and Old World strains analyzed and visualized as a splits tree built using genomewide single-nucleotide polymorphisms in SplitsTree 6 (17). A) The cluster of the L. donovani complex is found at the top of the tree (blue) and the L. tropica are found at the bottom (orange). B) Phylogenetic network analysis of only the L. tropica genomes in our dataset. Orange squares, L. tropica isolates from Sri Lanka (HS1, H9–34); black font, Middle Eastern L. tropica; gray font, Azerbaijan (SAFK27) (8), Morocco (Ltr16) (21), and Afghanistan (Rupert) (8); red font, Indian L. tropica (K26 and K112) (8). Scale bar represents nucleotide substitutions per position.

Figure 5. Phylogenetic network of all Leishmania isolates from Sri Lanka and Old World strains analyzed and visualized as a splits tree built using genomewide single-nucleotide polymorphisms in SplitsTree 6 (17). A) The cluster of the L. donovani complex is found at the top of the tree (blue) and the L. tropica are found at the bottom (orange). B) Phylogenetic network analysis of only the L. tropica genomes in our dataset. Orange squares, L. tropica isolates from Sri Lanka (HS1, H9–34); black font, Middle Eastern L. tropica; gray font, Azerbaijan (SAFK27) (8), Morocco (Ltr16) (21), and Afghanistan (Rupert) (8); red font, Indian L. tropica (K26 and K112) (8). Scale bar represents nucleotide substitutions per position.

Main Article

References
  1. Desjeux  P. Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis. 2004;27:305–18. DOIPubMedGoogle Scholar
  2. Alvar  J, Yactayo  S, Bern  C. Leishmaniasis and poverty. Trends Parasitol. 2006;22:552–7. DOIPubMedGoogle Scholar
  3. Karunaweera  ND, Pratlong  F, Siriwardane  HVYD, Ihalamulla  RL, Dedet  JP. Sri Lankan cutaneous leishmaniasis is caused by Leishmania donovani zymodeme MON-37. Trans R Soc Trop Med Hyg. 2003;97:380–1. DOIPubMedGoogle Scholar
  4. Siriwardana  HVYD, Karunanayake  P, Goonerathne  L, Karunaweera  ND. Emergence of visceral leishmaniasis in Sri Lanka: a newly established health threat. Pathog Glob Health. 2017;111:317–26. DOIPubMedGoogle Scholar
  5. Karunaweera  ND, Senanayake  S, Ginige  S, Silva  H, Manamperi  N, Samaranayake  N, et al. Spatiotemporal distribution of cutaneous leishmaniasis in Sri Lanka and future case burden estimates. PLoS Negl Trop Dis. 2021;15:e0009346. DOIPubMedGoogle Scholar
  6. Zhang  WW, Ramasamy  G, McCall  LI, Haydock  A, Ranasinghe  S, Abeygunasekara  P, et al. Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain. PLoS Pathog. 2014;10:e1004244. DOIPubMedGoogle Scholar
  7. Sterkers  Y, Lachaud  L, Crobu  L, Bastien  P, Pagès  M. FISH analysis reveals aneuploidy and continual generation of chromosomal mosaicism in Leishmania major. Cell Microbiol. 2011;13:274–83. DOIPubMedGoogle Scholar
  8. Iantorno  SA, Durrant  C, Khan  A, Sanders  MJ, Beverley  SM, Warren  WC, et al. Gene expression in Leishmania is regulated predominantly by gene dosage. MBio. 2017;8:1–20. DOIPubMedGoogle Scholar
  9. Burza  S, Croft  SL, Boelaert  M. Leishmaniasis. Lancet. 2018;392:951–70. DOIPubMedGoogle Scholar
  10. Lypaczewski  P, Thakur  L, Jain  A, Kumari  S, Paulini  K, Matlashewski  G, et al. An intraspecies Leishmania donovani hybrid from the Indian subcontinent is associated with an atypical phenotype of cutaneous disease. iScience. 2022;25:103802. DOIPubMedGoogle Scholar
  11. Inbar  E, Shaik  J, Iantorno  SA, Romano  A, Nzelu  CO, Owens  K, et al. Whole genome sequencing of experimental hybrids supports meiosis-like sexual recombination in Leishmania. PLoS Genet. 2019;15:e1008042. DOIPubMedGoogle Scholar
  12. Karunaweera  ND. Leishmania donovani causing cutaneous leishmaniasis in Sri Lanka: a wolf in sheep’s clothing? Trends Parasitol. 2009;25:458–63. DOIPubMedGoogle Scholar
  13. Lypaczewski  P, Matlashewski  G. Leishmania donovani hybridisation and introgression in nature: a comparative genomic investigation. Lancet Microbe. 2021;2:e250–8. DOIPubMedGoogle Scholar
  14. Zemanová  E, Jirků  M, Mauricio  IL, Horák  A, Miles  MA, Lukeš  J. The Leishmania donovani complex: genotypes of five metabolic enzymes (ICD, ME, MPI, G6PDH, and FH), new targets for multilocus sequence typing. Int J Parasitol. 2007;37:149–60. DOIPubMedGoogle Scholar
  15. Kumar  S, Stecher  G, Li  M, Knyaz  C, Tamura  K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol. 2018;35:1547–9. DOIPubMedGoogle Scholar
  16. Shaik  JS, Dobson  DE, Sacks  DL, Beverley  SM. Leishmania sexual reproductive strategies as resolved through computational methods designed for aneuploid genomes. Genes (Basel). 2021;12:1–16. DOIPubMedGoogle Scholar
  17. Huson  DH, Bryant  D. Application of phylogenetic networks in evolutionary studies. Mol Biol Evol. 2006;23:254–67. DOIPubMedGoogle Scholar
  18. Salloum  T, Moussa  R, Rahy  R, Al Deek  J, Khalifeh  I, El Hajj  R, et al. Expanded genome-wide comparisons give novel insights into population structure and genetic heterogeneity of Leishmania tropica complex. PLoS Negl Trop Dis. 2020;14:e0008684. DOIPubMedGoogle Scholar
  19. Dumetz  F, Imamura  H, Sanders  M, Seblova  V, Myskova  J, Pescher  P, et al. Modulation of aneuploidy in Leishmania donovani during adaptation to different in vitro and in vivo environments and its impact on gene expression. MBio. 2017;8:1–14. DOIPubMedGoogle Scholar
  20. Ferreira  TR, Inbar  E, Shaik  J, Jeffrey  BM, Ghosh  K, Dobson  DE, et al. Self-Hybridization in Leishmania major. MBio. 2022;13:e0285822. DOIPubMedGoogle Scholar
  21. Bussotti  G, Gouzelou  E, Côrtes Boité  M, Kherachi  I, Harrat  Z, Eddaikra  N, et al. Leishmania genome dynamics during environmental adaptation reveal strain-specific differences in gene copy number variation, karyotype instability, and telomeric amplification. MBio. 2018;9:1–18. DOIPubMedGoogle Scholar
  22. Krzywinski  M, Schein  J, Birol  I, Connors  J, Gascoyne  R, Horsman  D, et al. Circos: an information aesthetic for comparative genomics. Genome Res. 2009;19:1639–45. DOIPubMedGoogle Scholar
  23. Samarasinghe  SR, Samaranayake  N, Kariyawasam  UL, Siriwardana  YD, Imamura  H, Karunaweera  ND. Genomic insights into virulence mechanisms of Leishmania donovani: evidence from an atypical strain. BMC Genomics. 2018;19:843. DOIPubMedGoogle Scholar
  24. Robinson  JT, Thorvaldsdóttir  H, Winckler  W, Guttman  M, Lander  ES, Getz  G, et al. Integrative genomics viewer. Nat Biotechnol. 2011;29:24–6. DOIPubMedGoogle Scholar
  25. Shirian  S, Oryan  A, Hatam  GR, Daneshbod  Y. Three Leishmania/L. species—L. infantum, L. major, L. tropica—as causative agents of mucosal leishmaniasis in Iran. Pathog Glob Health. 2013;107:267–72. DOIPubMedGoogle Scholar
  26. Shirian  S, Oryan  A, Hatam  GR, Daneshbod  K, Daneshbod  Y. Molecular diagnosis and species identification of mucosal leishmaniasis in Iran and correlation with cytological findings. Acta Cytol. 2012;56:304–9. DOIPubMedGoogle Scholar
  27. Bussotti  G, Li  B, Pescher  P, Vojtkova  B, Louradour  I, Pruzinova  K, et al. Leishmania allelic selection during experimental sand fly infection correlates with mutational signatures of oxidative DNA damage. Proc Natl Acad Sci U S A. 2023;120:e2220828120. DOIPubMedGoogle Scholar
  28. Waitz  Y, Paz  S, Meir  D, Malkinson  D. Effects of land use type, spatial patterns and host presence on Leishmania tropica vectors activity. Parasit Vectors. 2019;12:320. DOIPubMedGoogle Scholar
  29. Sohrabi  Y, Havelková  H, Kobets  T, Šíma  M, Volkova  V, Grekov  I, et al. Mapping the genes for susceptibility and response to Leishmania tropica in mouse. PLoS Negl Trop Dis. 2013;7:e2282. DOIPubMedGoogle Scholar
  30. Magill  AJ, Grögl  M, Gasser  RA Jr, Sun  W, Oster  CN. Visceral infection caused by Leishmania tropica in veterans of Operation Desert Storm. N Engl J Med. 1993;328:1383–7. DOIPubMedGoogle Scholar
  31. Sacks  DL, Kenney  RT, Kreutzer  RD, Jaffe  CL, Gupta  AK, Sharma  MC, et al. Indian kala-azar caused by Leishmania tropica. Lancet. 1995;345:959–61. DOIPubMedGoogle Scholar
  32. Ghedin  E, Zhang  WW, Charest  H, Sundar  S, Kenney  RT, Matlashewski  G. Antibody response against a Leishmania donovani amastigote-stage-specific protein in patients with visceral leishmaniasis. Clin Diagn Lab Immunol. 1997;4:530–5. DOIPubMedGoogle Scholar
  33. Zhang  WW, Matlashewski  G. Characterization of the A2-A2rel gene cluster in Leishmania donovani: involvement of A2 in visceralization during infection. Mol Microbiol. 2001;39:935–48. DOIPubMedGoogle Scholar
  34. McCall  LI, Matlashewski  G. Localization and induction of the A2 virulence factor in Leishmania: evidence that A2 is a stress response protein. Mol Microbiol. 2010;77:518–30. DOIPubMedGoogle Scholar
  35. Al-Khalaifah  HS. Major molecular factors related to Leishmania pathogenicity. Front Immunol. 2022;13:847797. DOIPubMedGoogle Scholar
  36. Khan  NH, Llewellyn  MS, Schönian  G, Sutherland  CJ. Variability of cutaneous leishmaniasis lesions is not associated with genetic diversity of Leishmania tropica in Khyber Pakhtunkhwa province of Pakistan. Am J Trop Med Hyg. 2017;97:1489–97. DOIPubMedGoogle Scholar
  37. De Silva  NL, De Silva  VNH, Deerasinghe  ATH, Rathnapala  UL, Itoh  M, Takagi  H, et al. Development of a highly sensitive nested PCR and its application for the diagnosis of cutaneous leishmaniasis in Sri Lanka. Microorganisms. 2022;10:990. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.

Page created: August 07, 2024
Page updated: August 20, 2024
Page reviewed: August 20, 2024
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external