4.5 Article

Enhancing the copy number of Ldrab6 gene in Leishmania donovani parasites mediates drug resistance through drug-thiol conjugate dependent multidrug resistance protein A (MRPA)

期刊

ACTA TROPICA
卷 199, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.actatropica.2019.105158

关键词

Leishmania donovani; Drug resistance; MRPA; Rab6 protein

资金

  1. Council of Scientific and Industrial Research (CSIR), India [BSC-0114]
  2. Indian Council of Medical Research (ICMR)

向作者/读者索取更多资源

Visceral leishmaniasis (VL) is a neglected tropical disease caused by protozoan Leishmania donovani parasite which may be fatal if left untreated. While drug-sensitive parasites are able to live and multiply within the host macrophages, they develop resistance to drugs used against them for survival and multiplication in the infected patients undergoing routine treatment. Development of new agents devoid of such drug resistance potential is achievable by identifying new drug targets in the parasite. One such target is the key regulator of intracellular vesicular trafficking protein, RabGTPase which belongs to the Ras GTPase superfamily. We recently elucidated whole genome sequence (WGS) of L. donovani (clinical Indian isolate; BHU 1220, GenBank: AVPQ00000000.1) and identified Ldrab6 gene. We now provide experimental evidence for this gene's ability to impart drug-resistant phenotype to wild-type (sensitive) Leishmania upon transfection. trans-Dibenzalacetone (DBA), a synthetic analog of curcumin, was used to determine its antileishmanial activity in wild-type parasites and parasites transfected with Ldrab6 gene. Dose-response study showed that DBA had no effect on transfected parasites at 20 mu g/mL dose, whereas wild-type promastigotes showed 50% inhibition (IC50) at the same dose. This indicates the development of resistant mechanism in the transfected parasites due to enhancement of the copy number of Ldrab6 gene in L. donovani parasites. Flow cytometric analysis revealed elevated level of thiols in transfectants when compared to wild-type parasites treated with DBA. To assess the functional activity of multidrug resistance-associated protein (MRP) pump in transfectants, the accumulation of calcein, a known MRP pump substrate and probenecid, a known MRP pump regulator, were analyzed. The results indicate that Ldrab6 gene in Leishmania conferred resistance by the well-established mechanism of drug-thiol conjugation and sequestration by ABC transporter multidrug resistance-protein A (MRPA). Accordingly, Leishmania parasites transfected with Ldrab6 gene can be used as an experimental cell line for the screening of new lead molecules for their propensity to develop drug resistance.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
Article Parasitology

Epidemiological profile and genetic resistance of Neisseria gonorrhoeae infection in women in a poor region of Sao Paulo, Brazil

Gabriela Martinez Moura Tavares, Hannar Angelica de Melo Alverga, Estela Moraes Felix, Giovana de Oliveira Dichman, Gabriel Monteiro Pinheiro, Yara Juliano, Priscila Paruci, Dennis Minoru Fujita, Lucas Melo Neves, Marina Tiemi Shio, Luiz Henrique da Silva Nali

Summary: This study investigated the frequency of N. gonorrhoeae infection in women in a poor area of São Paulo and found that most of the strains detected showed resistance to one or more antimicrobials.

ACTA TROPICA (2024)

Article Parasitology

MiR-4521 affects the propagation of Cryptosporidium parvum in HCT-8 cells through targeting foxm1 by regulating cell apoptosis

Qian Yao, Ying-Ying Fan, Shuang Huang, Gui-Rong Hu, Jun-Ke Song, Xin Yang, Guang-Hui Zhao

Summary: This study found that the expression of miR-4521 was upregulated during C. parvum infection, and this upregulation was related to the TLR/NF-kappa B signal pathway. Additionally, miR-4521 promoted the propagation of C. parvum in HCT-8 cells by regulating BCL2-mediated cell apoptosis through targeting foxm1.

ACTA TROPICA (2024)

Article Parasitology

Prevalence of zoonotic (brugian) filariasis in Asia: A proportional meta-analysis

Cho Naing, Maxine A. Whittaker, Wong Siew Tung, Htar Aung, Joon Wah Mak

Summary: This study aimed to estimate the prevalence of zoonotic brugian filariasis in animals and compare it with the prevalence in humans in the same area. The findings suggest that cats, dogs, and leaf-eating monkeys may serve as potential reservoirs for human brugian filariasis.

ACTA TROPICA (2024)

Review Parasitology

Looking through the lens of social science approaches: A scoping review of leishmaniases and Chagas disease research

Raissa Nogueira de Brito, Susan Tanner, Julie Velasquez Runk, Juliana Hoyos

Summary: This study conducted a scoping review to identify major research themes and knowledge gaps in the social science literature on leishmaniases or Chagas disease. The findings showed that research in this field mainly focuses on the sociocultural, economic, historical, and political dimensions of the diseases. Future research should pay more attention to how social institutions and economic factors shape disease education, control measures, healthcare access, and quality of life of affected individuals.

ACTA TROPICA (2024)

Article Parasitology

Rapid, sensitive, and convenient detection of Plasmodium falciparum infection based on CRISPR and its application in detection of asymptomatic infection

Minghao Zheng, Mengyao Zhang, Hao Li, Shipo Wu, Yuee Zhao, Jinlong Zhang, Yunyue Zhou, Mohamed Boie Jalloh, Kun Zhang, Lina Chen, Zhiqiang Mi, Yong Cui, Lihua Hou

Summary: Rapid and convenient detection of Plasmodium falciparum, the deadliest malaria parasite in Africa, is crucial for malaria eradication efforts in medical resource-limited settings. A CRISPR-based diagnostic method that can detect P. falciparum without nucleic acid extraction was developed and showed high sensitivity and consistency with qPCR test. It can also detect artemisinin-resistant strains and other laboratory-cultured strains. This method has great potential for clinical testing and large-scale community screening in Africa and other regions.

ACTA TROPICA (2024)

Article Parasitology

West Nile virus in Mexico: Why vectors matter for explaining the current absence of epidemics

Fabian Correa-Morales, Cassandra Gonzalez-Acosta, David Ibarra-Ojeda, Miguel Moreno-Garcia

Summary: Since 2002, West Nile Virus (WNV) has been reported in 18 states in Mexico. This paper discusses the proposed hypotheses for the absence of WNV outbreaks in Latin America and provides a context-specific explanation for Mexico.

ACTA TROPICA (2024)

Article Parasitology

High detection frequency and genetic diversity of porcine circovirus 3 (PCV-3) in Namibian backyard farms and warthogs

Umberto Molini, Lauren M. Coetzee, Vernon Christians, Maria Y. Hemberger, Bernard Chiwome, Maria Amukwaya, Siegfried Khaiseb, Giovanni Cattoli, William G. Dundon, Giovanni Franzo

Summary: Porcine circovirus 3 (PCV-3) has been reported globally since its first identification in 2015. Limited data on PCV-3 in Africa led to a study in Namibia, which found a high prevalence of PCV-3 in backyard piggeries, but not in commercial farms with higher biosecurity measures. The source of viral introduction and factors such as semen importation, feeding backyard pigs with human food waste, pig exchanges, and wildlife movements may be involved in the dispersal of PCV-3 within Namibia. Further studies are needed to understand the epidemiology and impact of PCV-3 on pig productivity and wildlife health.

ACTA TROPICA (2024)

Article Parasitology

Natural SARS-CoV-2 infection in dogs: Determination of viral loads, distributions, localizations, and pathology

Chutchai Piewbang, Panida Poonsin, Pattiya Lohavicharn, Panitnan Punyathi, Sawang Kesdangsakonwut, Tanit Kasantikul, Somporn Techangamsuwan

Summary: This study provides insights into the pathology of natural SARS-CoV-2 infection in dogs, revealing severe damage to the lungs and involvement of multiple organs. The findings suggest the potential utility of dogs as a model for studying SARS-CoV-2 infection in humans, highlighting the need for further investigation.

ACTA TROPICA (2024)

Article Parasitology

The effect of El Nino and La Nina episodes on the existing niche and potential distribution of vector and host species of American Cutaneous Leishmaniasis

Julian Avila-Jimenez, Juan David Gutierrez, Mariano Altamiranda-Saavedra

Summary: Leishmaniasis is a parasitic disease transmitted to humans by sandfly vectors and vertebrate hosts. This study used ecological niche modeling to investigate the potential distribution of host and vector species associated with cutaneous leishmaniasis transmission, revealing different distribution patterns under varying climatic conditions.

ACTA TROPICA (2024)

Article Parasitology

Molecular survey of hemoplasmas in asymptomatic vicunas (Vicugna vicugna) from the Pampa Galeras Barbara D'Achille National Reserve in Peru

Luis A. Gomez-Puerta, Juan Olazabal, Santiago Paredes, Juan Lopez, Miguel Anampa, Angelica Mondragon, Ana Vargas-Calla, Hugo Castillo

Summary: This study reports the first detection of Candidatus M. haemolamae infection in vicunas from the Pampa Galeras National Reserve in Peru, using molecular diagnosis. Tick-infested vicunas had a higher likelihood of being infected with Candidatus M. haemolamae compared to tick-free vicunas. Gender and age were not associated with infection.

ACTA TROPICA (2024)

Article Parasitology

Biomarker of Anopheles exposure in Ghanaian children with hemoglobin S and C

Berlin Londono-Renteria, Zakaria Seidu, Helena Lamptey, Michael F. Ofori, Lars Hviid, Mary Lopez-Perez

Summary: Heterozygous carriers of HbAS and HbAC have a reduced risk of severe malaria, but not immunity against Plasmodium falciparum infection. Antibody levels against gSG6-P1 peptide in Anopheles mosquito saliva can serve as a serological biomarker for exposure to Plasmodium infection. This study highlights the importance of studying the role of hemoglobinopathies in malaria transmission for improving control interventions.

ACTA TROPICA (2024)

Article Parasitology

The APOBEC3G gene rs2294367(C>G) variant is associated with HIV-1 infection in Moroccan subjects

Imane Belbacha, Meryem El Azzouzi, Rajae Bensghir, Kamal Filali Marhoum, Khadija Hajjout, El Mir Elharti, Khalid Sadki, Hicham Oumzil

Summary: This study investigates the association of three SNPs in the APOBEC3G gene with disease outcomes in Moroccan HIV-1 infected patients. The rs2294367 CG genotype is strongly associated with protection against HIV-1 infection, particularly in older individuals.

ACTA TROPICA (2024)

Article Parasitology

Spatial analysis of human and livestock anthrax in Lai Chau province, Vietnam (2004-2021)

Tan Luong, Do Kien Tran, Anh Hung Pham, Thi Thu-Ha Hoang, Van Khang Pham, Quang Thai Pham, Thi Mai Hung Tran, Minh Hoa Luong, Thanh Long Pham, Jason K. Blackburn

Summary: This study examined the epidemiology of anthrax in Lai Chau province, Vietnam, using historical data. Spatial clusters of human and livestock anthrax were identified, and the characteristics of the disease were described. The study found that there were distinct differences between the high-risk areas for human and livestock anthrax, and most human cases occurred during specific seasons. Additionally, the decrease in livestock anthrax vaccine coverage was associated with an increase in disease incidence.

ACTA TROPICA (2024)

Article Parasitology

Diversity and genetic characterization of orthohantavirus from small mammals and humans during 2012-2022 in Hubei Province, Central China

Jin-tao Chen, Jian-bo Zhan, Ming-chao Zhu, Kai-ji Li, Man-qing Liu, Bin Hu, Kun Cai, Hai-rong Xiong, Shu-liang Chen, Wei-long Tan, Liang-jun Chen, Wei Hou

Summary: This study investigated the prevalence and variation of orthohantavirus in rodents and humans in Hubei province, China. It identified the diversity of orthohantaviruses circulating in the region, with the HV004-like subtype being the main genotype in rodents and patients. This highlights the importance of continued attention and research on orthohantaviruses, especially newly identified strains.

ACTA TROPICA (2024)