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Amphotericin B resistance correlates with increased fitness in vitro and in vivo in Leishmania (Mundinia) martiniquensis
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Document Title
Amphotericin B resistance correlates with increased fitness in vitro and in vivo in Leishmania (Mundinia) martiniquensis
Author
Mano C., Kongkaew A., Tippawangkosol P., Somboon P., Roytrakul S., Pescher P., Späth G.F., Uthaipibull C., Tantiworawit A., Siriyasatien P., Jariyapan N.
Affiliations
Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Animal House Unit, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand; Institut Pasteur, INSERM U1201, Université Paris Cité, Unité de Parasitologie Moléculaire et Signalisation, Paris, France; Thailand Center of Excellence for Life Sciences (TCELS), Bangkok, Thailand; Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Vector Biology and Vector-Borne Disease, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Type
Article
Source Title
Frontiers in Microbiology
ISSN
1664302X
Year
2023
Volume
14
Page
-
Open Access
All Open Access, Gold, Green
Publisher
Frontiers Media S.A.
DOI
10.3389/fmicb.2023.1156061
Format
Abstract
Amphotericin B (AmpB) deoxycholate is the available first-line drug used to treat visceral leishmaniasis caused by Leishmania (Mundinia) martiniquensis, however, some cases of AmpB treatment failure have been reported in Thailand. Resistance to drugs is known to affect parasite fitness with a potential impact on parasite transmission but still little is known about the effect of resistance to drugs on L. martiniquensis. Here we aimed to gain insight into the fitness changes occurring after treatment failure or in vitro-induced resistance to AmpB. L. martiniquensis parasites isolated from a patient before (LSCM1) and after relapse (LSCM1-6) were compared for in vitro and in vivo fitness changes together with an in vitro induced AmpB-resistant parasite generated from LSCM1 parasites (AmpBRP2i). Results revealed increased metacyclogenesis of the AmpBPR2i and LSCM1-6 strains (AmpB-resistant strains) compared to the LSCM1 strain and increased fitness with respect to growth and infectivity. The LSCM1-6 and AmpBRP2i strains were present in mice for longer periods compared to the LSCM1 strain, but no clinical signs of the disease were observed. These results suggest that the AmpB-resistant parasites could be more efficiently transmitted to humans and maintained in asymptomatic hosts longer than the susceptible strain. The asymptomatic hosts therefore may represent “reservoirs” for the resistant parasites enhancing transmission. The results in this study advocate an urgent need to search and monitor for AmpB-resistant L. martiniquensis in patients with relapsing leishmaniasis and in asymptomatic patients, especially, in HIV/Leishmania coinfected patients. Copyright © 2023 Mano, Kongkaew, Tippawangkosol, Somboon, Roytrakul, Pescher, Späth, Uthaipibull, Tantiworawit, Siriyasatien and Jariyapan.
Funding Sponsor
Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation; Ministry of Higher Education, Research and Innovation; The Ministry of Economic Affairs and Employment; Chiang Mai University; Chulalongkorn University; National Science and Technology Development Agency; Faculty of Agro-Industry, Chiang Mai University; Faculty of Veterinary Medicine, Chiang Mai University; Thailand Graduate Institute of Science and Technology; Faculty of Science, Chiang Mai University; Graduate School, Chiang Mai University; Faculty of Medicine, Chiang Mai University; Ministry of Higher Education, Science, Research and Innovation, Thailand; Functional Food Research Center for Well-being, Chiang Mai University; Thailand Science Research and Innovation; Department of Chemistry, Faculty of Science, Chiang Mai University; Materials Science Research Center, Faculty of Science, Chiang Mai University; Faculty of Economics, Chiang Mai University; Department of Physics and Materials Science, Faculty of Science, Chiang Mai University
Publication Source
WOS