New insights in photodynamic inactivation of Leishmania amazonensis:
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The emergence of drug resistance in cutaneous leishmaniasis (CL) has become a major
problem over the past decades. The spread of resistant phenotypes has been attributed
to the wide misuse of current antileishmanial chemotherapy, which is a serious threat to
global health. Photodynamic therapy (PDT) has been shown to be effective against a wide
spectrum of drug-resistant pathogens. Due to its multi-target approach and immediate
effects, it may be an attractive strategy for treatment of drug-resistant Leishmania species. In this study, we sought to evaluate the activity of PDT in vitro using the photosensitizer 1,9-dimethyl methylene blue (DMMB), against promastigotes of two Leishmania
amazonensis strains: the wild-type (WT) and a lab induced miltefosine-resistant (MFR)
strain. The underlying mechanisms of DMMB-PDT action upon the parasites was focused
on the changes in the lipid metabolism of both strains, which was conducted by a quantitative lipidomics analysis. We also assessed the production of ROS, mitochondrial labeling
and lipid droplets accumulation after DMMB-PDT. Our results show that DMMB-PDT produced high levels of ROS, promoting mitochondrial membrane depolarization due to the
loss of membrane potential. In addition, both untreated strains revealed some differences
in the lipid content, in which MFR parasites showed increased levels of phosphatidylcholine, hence suggesting this could also be related to their mechanism of resistance to miltefosine. Moreover, the oxidative stress and consequent lipid peroxidation led to significant
phospholipid alterations, thereby resulting in cellular dysfunction and parasite death.
Thus, our results demonstrated that DMMB-mediated PDT is effective to kill L. amazonensis MFR strain and should be further studied as a potential strategy to overcome antileishmanial drug resistance.
Como referenciar
CABRAL, FERNANDA V.; CERONE, MICHELA; PERSHEYEV, SAYDULLA; LIAN, CHENG; SAMUEL, IFOR D.W.; RIBEIRO, MARTHA S.; SMITH, TERRY K. New insights in photodynamic inactivation of Leishmania amazonensis:: A focus on lipidomics and resistance. PLoS ONE, v. 18, n. 9, p. 1-23, 2023. DOI: 10.1371/journal.pone.0289492. Disponível em: http://repositorio.ipen.br/handle/123456789/34344. Acesso em: 30 Dec 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.