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Ponte-Sucre, Alicia

doi:10.1186/1475-9292-2-14

Cited by 38 publications

(13 citation statements)

References 73 publications

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“…The discovery of genes underpinning resistance to other drugs, including MIL and AmB, will similarly offer an ability to monitor the emergence and spread of resistance to these drugs in the field as well. This will inform surveillance strategies to monitor drug efficacy and should feed into coordinated measures to enable further research and the setting of policies to optimize our capability to continue efforts to control the leishmaniases as a global health problem [ 146 ].…”

Section: General Conclusionmentioning

confidence: 99%

Drug resistance and treatment failure in leishmaniasis: A 21st century challenge

et al. 2017

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Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of “resistance” related to leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B, and miltefosine are also outlined.

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Section: General Conclusionmentioning

confidence: 99%

Drug resistance and treatment failure in leishmaniasis: A 21st century challenge

et al. 2017

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“…In case of leishmaniasis, drug resistant Leishmania strains have evolved mainly due to some physiological changes as well as some genetic changes (Fig. (3)) [23]. Pentavalent antimonial drugs are the first choice of drugs against leishmaniasis [24,25] although resistance is a growing problem [26][27][28][29].…”

Section: Drug Resistancementioning

confidence: 99%

A Novel Functional Approach Toward Identifying Definitive Drug Targets

Dey¹,

Khan²,

Saha

2007

CMC

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The process of developing drugs dates to antiquity. The herbal formulations during the old days were more traditional than with any scientific rationale. As different branches of physics, chemistry and biology started revealing the physiological processes in molecular details and as the sophisticated methods for probing into these phenomena were innovated, the processes of drug development changed significantly. However, the very first step in the process which is defining a drug target remains a major hurdle. The classical methods that predate the functional genomics and proteomics involve a cumbersome, painstaking detailing of a given enzyme or a receptor, followed by its validation as a target. The sophisticated methods in the post-genomic and proteomic era reduced the time taken to define targets, but the speed of drug discovery is not necessarily as quick as it promised. This is primarily due to prolific predictions pressing validation too hard, although both non-robotic and robotic high throughput screenings match with the requirement. Since these drugs target pathogens, a serious disadvantage with these methodologies is the emergence of drug resistance. Therefore, we propose a functional approach whereby the host-pathogen interaction is studied to find out the alterations in immune responses, the profile of host gene expression and activation of cell signaling molecules, the kinases in particular. Such interactions often induce the expression of those genes and activation of those proteins which are required for their survival. We demonstrate that reversal of such profiles of gene expression and protein activation ameliorates the infection. Therefore, those gene products and the kinases with pro-parasitic functions can serve as targets.

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“…Many studies also showed differences in tubulin levels in drug resistant parasites. It is possible that the physiological changes of resistant parasites modify several cellular pathways, directly affecting tubulin proteins or the events leading to cytoskeletal changes …”

Section: Potential Applications Of Proteomics In Leishmaniasismentioning

confidence: 99%

“…It is possible that the physiological changes of resistant parasites modify several cellular pathways, directly affecting tubulin proteins or the events leading to cytoskeletal changes. [116] A recent review has analyzed the use of proteomics for drug discovery for CL. [117] As stated previously, new proteomic studies are needed to validate the potential biomarkers and therapeutic targets, which must also be evaluated in terms of efficacy, safety, stability, quality control, and clinical assays.…”

Section: Proteomic Strategies To Discover Biological Basis Of Drug Rementioning

confidence: 99%

Proteomics and Leishmaniasis: Potential Clinical Applications

Capelli-Peixoto

Mule

Tano

et al. 2019

Proteomics Clinical Apps

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Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. They are endemic in 98 countries, affect around 12 million people worldwide and may present several distinct clinical forms. Unfortunately, there are only a few drugs available for treatment of leishmaniasis, which are toxic and not always effective. Different parasite species and different clinical forms require optimization of the treatment or more specific therapies, which are not available. The emergence of resistance is also a matter of concern. Besides, diagnosis can sometimes be complicated due to atypical manifestations and associations with other pathologies. In this review, proteomic data are presented and discussed in terms of their application in important issues in leishmaniasis such as parasite resistance to chemotherapy, diagnosis of active disease in patients and dogs, markers for different clinical forms, identification of virulence factors, and their potential use in vaccination. It is shown that proteomics has contributed to the discovery of potential biomarkers for prognosis, diagnosis, therapeutics, monitoring of disease progression, treatment follow‐up and identification of vaccine candidates for specific diseases. However, the authors believe its capabilities have not yet been fully explored for routine clinical analysis for several reasons, which will be presented in this review.

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Untitled

Cited by 38 publications

References 73 publications

Drug resistance and treatment failure in leishmaniasis: A 21st century challenge

Drug resistance and treatment failure in leishmaniasis: A 21st century challenge

A Novel Functional Approach Toward Identifying Definitive Drug Targets

Proteomics and Leishmaniasis: Potential Clinical Applications

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