Genome-wide analysis reveals allelic variation and chromosome copy number variation in paromomycin-resistant Leishmania donovani

Ghosh, Sambuddha; Kumar, Vinay; Verma, Aditya; Sharma, Tanya; Pradhan, Dibyabhaba; Selvapandiyan, Angamuthu; Salotra, Poonam; Singh, Ruchi

doi:10.1007/s00436-022-07645-x

Cited by 3 publications

(2 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from that plethora of genes, protein functions and metabolic pathways are interconnected with the arousal of Sb unresponsiveness, which is of greatest concern for its epidemiology and threatens to undermine disease control efforts. The differential gene expression and genetic modifications are of paramount importance for Leishmania in bringing about drug resistance, and such discrepancies are informative in predicting possible drug responses (Carter et al ., 2006; Kumar et al ., 2010; Torres et al ., 2010; Biyani et al ., 2011; Adaui et al ., 2011 a , 2011 b ; Oliaee et al ., 2018; Ghosh et al ., 2020, 2022). Often, the Sb resistance is accompanied by the transcriptional modifications of a certain set of genes that collaboratively interfere with the therapeutic effect of Sb detoxification through the incorporation of its active form into conjugates, and diminishing the intracellular Sb build up (Haimeur et al ., 2000).…”

Section: Introductionmentioning

confidence: 99%

Antimony resistance and gene expression inLeishmania: spotlight on molecular and proteomic aspects

Madusanka,

Karunaweera,

Silva

et al. 2023

Parasitology

Self Cite

View full text Add to dashboard Cite

Leishmaniasis is a vector-borne parasitic disease caused by Leishmania parasites with a spectrum of clinical manifestations, ranging from skin lesions to severe visceral complications. Treatment of this infection has been extremely challenging with the concurrent emergence of drug resistance. The differential gene expression and the discrepancies in protein functions contribute to the appearance of 2 distinct phenotypes: resistant and sensitive, but the current diagnostic tools fail to differentiate between them. The identification of gene expression patterns and molecular mechanisms coupled with antimony (Sb) resistance can be leveraged to prompt diagnosis and select the most effective treatment methods. The present study attempts to use comparative expression of Sb resistance-associated genes in resistant and sensitive Leishmania, to disclose their relative abundance in clinical or in vitro selected isolates to gain an understanding of the molecular mechanisms of Sb response/resistance. Data suggest that the analysis of resistance gene expression would verify the Sb resistance or susceptibility only to a certain extent; however, none of the individual expression patterns of the studied genes was diagnostic as a biomarker of Sb response of Leishmania. The findings highlighted will be useful in bridging the knowledge gap and discovering innovative diagnostic tools and novel therapeutic targets.

show abstract

Section: Introductionmentioning

confidence: 99%

Antimony resistance and gene expression inLeishmania: spotlight on molecular and proteomic aspects

Madusanka,

Karunaweera,

Silva

et al. 2023

Parasitology

Self Cite

View full text Add to dashboard Cite

show abstract

“…They require more time to become resistant to antiprotozoal drugs (Capela et al, 2019;Fernandes et al, 2022). The mechanism behind this includes polymorphism of single nucleotides, redundancy of proteins, and expression of genes in response to drugs (Ghosh et al,2022). Coccidiosis is primarily controlled using chemical and ionophore drugs (Adeyemi et al, 2023).…”

mentioning

confidence: 99%

Botanical control of coccidiosis in ruminants

Abbas

2023

PAKJAS

View full text Add to dashboard Cite

Coccidiosis is one of the major parasitic diseases infecting almost all ruminants, including cows, buffalo, sheep, and goats. Coccidiosis is caused by the genus Eimeria, which are host-specific obligate intestinal parasites. These are found almost all over the world and cause infections leading to mortalities and morbidities. Coccidiosis is usually treated by ionophores and synthetic chemicals of various classes including ionophores and synthetic chemical drugs. These drugs have been effective against coccidiosis but emerging issues of anthelmintic resistance, public health concerns, and consumer demand for organic products are leading to minimizing the use of these drugs. Vaccination is also being used, but vaccine failure and high cost limit their use. Among alternatives, herbal medicines are promising replacements because of their complex formulations, multiple modes of action, easy availability, and cost-effectiveness. Various plants, their parts, various formulations like herbal preparations, and the active compounds found in them are being searched to control ruminant coccidiosis. Multiple groups of botanical formulations, i.e., Flavonoids, alkaloids, tannins, terpenes, sulfur compounds, etc. have been proven to be effective against the ruminant coccidiosis-causing agents. They can control various stages of Eimeria directly and indirectly by antioxidant and immunomodulatory actions. Further research is needed to determine the most suitable herbal preparations and their pharmacological interactions for the effective and sustainable control of coccidiosis in ruminants. This review highlights the significance of ruminant coccidiosis, botanical compounds used against ruminant coccidiosis their mechanisms of action, and reasons and benefits of herbal compounds.

show abstract

Comprehensive analysis of flavohemoprotein copy number variation in Giardia intestinalis: exploring links to metronidazole resistance

Korenková,

Weisz,

Perglerová

et al. 2024

Parasites Vectors

View full text Add to dashboard Cite

Background Giardiasis, caused by the protozoan parasite Giardia intestinalis, often presents a treatment challenge, particularly in terms of resistance to metronidazole. Despite extensive research, markers for metronidazole resistance have not yet been identified. Methods This study analysed 28 clinical samples of G. intestinalis from sub-assemblage AII, characterised by varying responses to metronidazole treatment. We focussed on copy number variation (CNV) of the multi-copy flavohemoprotein gene, analysed using digital polymerase chain reaction (dPCR) and next generation sequencing (NGS). Additionally, chromosomal ploidy was tested in 18 of these samples. Flavohemoprotein CNV was also assessed in 17 samples from other sub-assemblages. Results Analyses revealed variable CNVs of the flavohemoprotein gene among the isolates, with no correlation to clinical metronidazole resistance. Discrepancies in CNVs detected from NGS data were attributed to biases linked to the whole genome amplification. However, dPCR helped to clarify these discrepancies by providing more consistent CNV data. Significant differences in flavohemoprotein CNVs were observed across different G. intestinalis sub-assemblages. Notably, Giardia exhibits a propensity for aneuploidy, contributing to genomic variability within and between sub-assemblages. Conclusions The complexity of the clinical metronidazole resistance in Giardia is influenced by multiple genetic factors, including CNVs and aneuploidy. No significant differences in the CNV of the flavohemoprotein gene between isolates from metronidazole-resistant and metronidazole-sensitive cases of giardiasis were found, underscoring the need for further research to identify reliable genetic markers for resistance. We demonstrate that dPCR and NGS are robust methods for analysing CNVs and provide cross-validating results, highlighting their utility in the genetic analyses of this parasite. Graphical Abstract

show abstract

Genome-wide analysis reveals allelic variation and chromosome copy number variation in paromomycin-resistant Leishmania donovani

Cited by 3 publications

References 85 publications

Antimony resistance and gene expression inLeishmania: spotlight on molecular and proteomic aspects

Antimony resistance and gene expression inLeishmania: spotlight on molecular and proteomic aspects

Botanical control of coccidiosis in ruminants

Comprehensive analysis of flavohemoprotein copy number variation in Giardia intestinalis: exploring links to metronidazole resistance

Contact Info

Product

Resources

About