In Vivo Bioluminescent Monitoring of Parasites in BALB/c Mouse Models of Cutaneous Leishmaniasis Drug Discovery
Confirming the in vivo efficacy of potential antileishmanial compounds that display in vitro potency and good chemical characteristics is one of the most important steps in preclinical research drug discovery before human clinical trials begin. Here we describe the use of the in vivo bioluminescent monitoring of high and low inocula of luciferase-expressing Leishmania major (L. major) parasites in traditional and more innovative rodent models of in vivo cutaneous leishmaniasis (CL) drug discovery.
Key wordsCutaneous leishmaniasis (CL) Rodent models In vivo imaging IVIS Bioluminescence signal Luciferase-expressing Leishmania major Drug efficacy Base of the tail Footpad Ear infections
Disclaimer: Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense.
Research was conducted under an approved animal use protocol in an AAALACi accredited facility in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, NRC Publication, 2011 edition.
- 1.World Health Organization (2010) Control of the leishmaniases. World Health Organ Tech Rep Ser 949:xii–xiii 1-186Google Scholar
- 3.Pigott DM, Bhatt S, Golding N et al (2014) Global distribution maps of the leishmaniases. Elife 3. https://doi.org/10.7554/eLife.02851
- 8.Ribeiro-Romao RP, Moreira OC, Osorio EY et al (2014) Comparative evaluation of lesion development, tissue damage, and cytokine expression in golden hamsters (Mesocricetus auratus) infected by inocula with different Leishmania (Viannia) braziliensis concentrations. Infect Immun 82(12):5203–5213. https://doi.org/10.1128/IAI.02083-14CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Lang T, Goyard S, Lebastard M, Milon G (2005) Bioluminescent Leishmania expressing luciferase for rapid and high throughput screening of drugs acting on amastigote-harbouring macrophages and for quantitative real-time monitoring of parasitism features in living mice. Cell Microbiol 7(3):383–392. https://doi.org/10.1111/j.1462-5822.2004.00468CrossRefPubMedGoogle Scholar
- 17.Caridha D, Parriot S, Hudson TH et al (2017) Use of optical imaging technology in the validation of a new, rapid, cost-effective drug screen as part of a tiered in vivo screening paradigm for development of drugs to treat cutaneous leishmaniasis. Antimicrob Agents Chemother 61(4):e02048-16. https://doi.org/10.1128/AAC.02048-16CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Schuster S, Hartley MA, Tacchini-Cottier F, Ronet C (2014) A scoring method to standardize lesion monitoring following intra-dermal infection of Leishmania parasites in the murine ear. Front Cell Infect Microbiol 4:67. https://doi.org/10.3389/fcimb.2014.00067CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Lecoeur H, Buffet PA, Milon G, Lang T (2010) Early curative applications of the aminoglycoside WR279396 on an experimental Leishmania major-loaded cutaneous site do not impair the acquisition of immunity. Antimicrob Agents Chemother 54(3):984–990. https://doi.org/10.1128/AAC.01310-09CrossRefPubMedGoogle Scholar
- 21.Sacks DL, Melby PC (2001) Animal models for the analysis of immune response to leishmaniasis. Curr Protoc Immunol . Chapter 19: Unit 19.2. https://doi.org/10.1002/0471142735.im1902s28