Global Distribution of Treatment Resistance Gene Markers for Leishmaniasis

Overview

Journal J Clin Lab Anal

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
Pathology

Date 2022 Jul 9

PMID 35808933

Authors

Samira Salari

Mehdi Bamorovat

Iraj Sharifi

Pooya Ghasemi Nejad Almani

Affiliations

Soon will be listed here.

Abstract

Background: Pentavalent antimonials (Sb(V)) such as meglumine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®) are used as first-line treatments for leishmaniasis, either alone or in combination with second-line drugs such as amphotericin B (Amp B), miltefosine (MIL), methotrexate (MTX), or cryotherapy. Therapeutic aspects of these drugs are now challenged because of clinical resistance worldwide.

Methods: We reviewedthe recent original studies were assessed by searching in electronic databases such as Scopus, Pubmed, Embase, and Web of Science.

Results: Studies on molecular biomarkers involved in drug resistance are essential for monitoring the disease. We reviewed genes and mechanisms of resistance to leishmaniasis, and the geographical distribution of these biomarkers in each country has also been thoroughly investigated.

Conclusion: Due to the emergence of resistant genes mainly in anthroponotic Leishmania species such as L. donovani and L. tropica, as the causative agents of ACL and AVL, respectively, selection of an appropriate treatment modality is essential. Physicians should be aware of the presence of such resistance for the selection of proper treatment modalities in endemic countries.

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References

Ubeda J, Legare D, Raymond F, Ouameur A, Boisvert S, Rigault P . Modulation of gene expression in drug resistant Leishmania is associated with gene amplification, gene deletion and chromosome aneuploidy. Genome Biol. 2008; 9(7):R115. PMC: 2530873. DOI: 10.1186/gb-2008-9-7-r115. View

Tessarollo N, Andrade J, Moreira D, Murta S . Functional analysis of iron superoxide dismutase-A in wild-type and antimony-resistant Leishmania braziliensis and Leishmania infantum lines. Parasitol Int. 2014; 64(2):125-9. DOI: 10.1016/j.parint.2014.11.001. View

Gomez-Arreaza A, Acosta H, Barros-Alvarez X, Concepcion J, Albericio F, Avilan L . Leishmania mexicana: LACK (Leishmania homolog of receptors for activated C-kinase) is a plasminogen binding protein. Exp Parasitol. 2011; 127(4):752-61. DOI: 10.1016/j.exppara.2011.01.008. View

Rusnak F, Mertz P . Calcineurin: form and function. Physiol Rev. 2000; 80(4):1483-521. DOI: 10.1152/physrev.2000.80.4.1483. View

Welchman R, Gordon C, Mayer R . Ubiquitin and ubiquitin-like proteins as multifunctional signals. Nat Rev Mol Cell Biol. 2005; 6(8):599-609. DOI: 10.1038/nrm1700. View

Perez-Victoria J, Parodi-Talice A, Jimenez I, Ravelo A, Castanys S, Gamarro F . Alkyl-lysophospholipid resistance in multidrug-resistant Leishmania tropica and chemosensitization by a novel P-glycoprotein-like transporter modulator. Antimicrob Agents Chemother. 2001; 45(9):2468-74. PMC: 90679. DOI: 10.1128/AAC.45.9.2468-2474.2001. View

Wyllie S, Vickers T, Fairlamb A . Roles of trypanothione S-transferase and tryparedoxin peroxidase in resistance to antimonials. Antimicrob Agents Chemother. 2008; 52(4):1359-65. PMC: 2292513. DOI: 10.1128/AAC.01563-07. View

Thakur C, Kanyok T, Pandey A, Sinha G, Zaniewski A, Houlihan H . A prospective randomized, comparative, open-label trial of the safety and efficacy of paromomycin (aminosidine) plus sodium stibogluconate versus sodium stibogluconate alone for the treatment of visceral leishmaniasis. Trans R Soc Trop Med Hyg. 2000; 94(4):429-31. DOI: 10.1016/s0035-9203(00)90130-5. View

Perez-Victoria J, Parodi-Talice A, Torres C, Gamarro F, Castanys S . ABC transporters in the protozoan parasite Leishmania. Int Microbiol. 2002; 4(3):159-66. DOI: 10.1007/s10123-001-0031-2. View

10.

Kumar A, Sisodia B, Misra P, Sundar S, Shasany A, Dube A . Proteome mapping of overexpressed membrane-enriched and cytosolic proteins in sodium antimony gluconate (SAG) resistant clinical isolate of Leishmania donovani. Br J Clin Pharmacol. 2010; 70(4):609-17. PMC: 2950996. DOI: 10.1111/j.1365-2125.2010.03716.x. View

11.

Nuhs A, Schafer C, Zander D, Trube L, Nevado P, Schmidt S . A novel marker, ARM58, confers antimony resistance to Leishmania spp. Int J Parasitol Drugs Drug Resist. 2014; 4(1):37-47. PMC: 3940081. DOI: 10.1016/j.ijpddr.2013.11.004. View

12.

Ersfeld K, Barraclough H, Gull K . Evolutionary relationships and protein domain architecture in an expanded calpain superfamily in kinetoplastid parasites. J Mol Evol. 2005; 61(6):742-57. DOI: 10.1007/s00239-004-0272-8. View

13.

Mukhopadhyay R, Dey S, Xu N, Gage D, Lightbody J, Ouellette M . Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania. Proc Natl Acad Sci U S A. 1996; 93(19):10383-7. PMC: 38393. DOI: 10.1073/pnas.93.19.10383. View

14.

Berberich C, Machado G, Morales G, Carrillo G, Jimenez-Ruiz A, Alonso C . The expression of the Leishmania infantum KMP-11 protein is developmentally regulated and stage specific. Biochim Biophys Acta. 1998; 1442(2-3):230-7. DOI: 10.1016/s0167-4781(98)00176-6. View

15.

Dhein J, Walczak H, Baumler C, Debatin K, Krammer P . Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature. 1995; 373(6513):438-41. DOI: 10.1038/373438a0. View

16.

Sezavar M, Sharifi I, Almani P, Kazemi B, Davoudi N, Salari S . The potential therapeutic role of PTR1 gene in non-healing anthroponotic cutaneous leishmaniasis due to Leishmania tropica. J Clin Lab Anal. 2020; 35(3):e23670. PMC: 7957997. DOI: 10.1002/jcla.23670. View

17.

Bishopric N, Andreka P, Slepak T, Webster K . Molecular mechanisms of apoptosis in the cardiac myocyte. Curr Opin Pharmacol. 2001; 1(2):141-50. DOI: 10.1016/s1471-4892(01)00032-7. View

18.

Brochu C, Haimeur A, Ouellette M . The heat shock protein HSP70 and heat shock cognate protein HSC70 contribute to antimony tolerance in the protozoan parasite leishmania. Cell Stress Chaperones. 2004; 9(3):294-303. PMC: 1065288. DOI: 10.1379/csc-15r1.1. View

19.

Ulrich N, Ephros M, Zilberstein D . Novel Intracellular SbV reducing activity correlates with antimony susceptibility in Leishmania donovani. J Biol Chem. 2000; 276(6):3971-6. DOI: 10.1074/jbc.M005423200. View

20.

Blankenship J, Wormley F, Boyce M, Schell W, Filler S, Perfect J . Calcineurin is essential for Candida albicans survival in serum and virulence. Eukaryot Cell. 2003; 2(3):422-30. PMC: 161442. DOI: 10.1128/EC.2.3.422-430.2003. View