A Guide to Next Generation Sequence Analysis of Leishmania Genomes

Imamura, Hideo; Dujardin, Jean‐Claude

doi:10.1007/978-1-4939-9210-2_3

Cited by 7 publications

(6 citation statements)

References 46 publications

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“…The development of virulence and resistance in L. donovani is essentially environmental selections of genomic variations allowing for fitness gain. Identifying such variations at DNA level would be useful to unravel the mechanisms underlying pathogenicity and drug resistance, which can be achieved nowadays by high-throughput next generation sequencing of genomic DNA and comparative analyses between/among strains [43]. For instance, a recent longitudinal genome analyses of 10 clinical isolates of Leishmania species have shown that gain and loss of gene copies might be the drivers of strain-specific phenotypic variations [27].…”

Section: Discussionmentioning

confidence: 99%

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Zheng

Chen

et al. 2020

Parasites Vectors

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Background Leishmaniasis is a neglected tropical disease affecting millions of people worldwide. Emerging drug resistance of Leishmania species poses threaten to the effective control and elimination programme of this neglected tropical disease. Methods In this work, we conducted drug-resistance testing, whole genome resequencing and proteome profiling for a recently reported clinical isolate with supposed drug resistance (HCZ), and two reference sensitive strains (DD8 and 9044) of Leishmania donovani, to explore molecular mechanisms underlying drug resistance in this parasite. Results With reference to DD8 and 9044 strains, HCZ isolate showed higher-level virulence and clear resistance to antimonials in promastigote culture, infected macrophages and animal experiment. Pairwise genomic comparisons revealed genetic variations (86 copy number variations, 271 frameshift mutations in protein-coding genes and two site mutations in non-coding genes) in HCZ isolate that were absent from the reference sensitive strains. Proteomic analysis indicated different protein expression between HCZ isolate and reference strains, including 69 exclusively detected proteins and 82 consistently down-/upregulated molecules in the HCZ isolate. Integrative analysis showed linkage of 12 genomic variations (gene duplication, insertion and deletion) and their protein expression changes in HCZ isolate, which might be associated with pathogenic and antimony-resistant phenotype. Functional annotation analyses further indicated that molecules involved in nucleotide-binding, fatty acid metabolism, oxidation-reduction and transport might play a role in host-parasite interaction and drug-resistance. Conclusions This comprehensive integrative work provided novel insights into the genetic basis underlying virulence and resistance, suggesting new aspects to be investigated for a better intervention against L. donovani and associated diseases.

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Section: Discussionmentioning

confidence: 99%

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Zheng

Chen

et al. 2020

Parasites Vectors

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“…One type of NGS couples WGS with MLST, and is a methodological advance for the provision of standardised epidemiological, molecular evolution and pathogenicity data [ 222 ]. Aneuploidy, which is observed in laboratory cultivated samples, as well as mosaicism, can be challenging in WGS, and thus read depth is critical for correct interpretation of Leishmania NGS data [ 223 – 225 ].…”

Section: Methods For the Identification Of Species Of Leish...mentioning

confidence: 99%

Laboratory diagnostics for human Leishmania infections: a polymerase chain reaction-focussed review of detection and identification methods

et al. 2022

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Leishmania infections span a range of clinical syndromes and impact humans from many geographic foci, but primarily the world’s poorest regions. Transmitted by the bite of a female sand fly, Leishmania infections are increasing with human movement (due to international travel and war) as well as with shifts in vector habitat (due to climate change). Accurate diagnosis of the 20 or so species of Leishmania that infect humans can lead to the successful treatment of infections and, importantly, their prevention through modelling and intervention programs. A multitude of laboratory techniques for the detection of Leishmania have been developed over the past few decades, and although many have drawbacks, several of them show promise, particularly molecular methods like polymerase chain reaction. This review provides an overview of the methods available to diagnostic laboratories, from traditional techniques to the now-preferred molecular techniques, with an emphasis on polymerase chain reaction-based detection and typing methods. Graphical abstract

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“…The individual chromosomal ploidy is highly varied as it can occur between one to six sister chromosomes within leishmanial populations ( Mannaert et al., 2012 ; Lachaud et al., 2014 ; Sterkers et al., 2014 ). Intermediate fold values of the NGS read alignment density can signal mosaic aneuploidy, such as the occurrence of population variations or incomplete chromosomal duplication occurrences ( Imamura and Dujardin, 2019 ). Drug resistance via aneuploidy has been intensively investigated and due to decades of use of pentavalent antimony-based drugs in endemic areas, resistance has developed, making these drugs nearly obsolete in some locations ( Dube et al., 2005 ; Croft et al., 2006 ; Singh et al., 2006 ; Ostyn et al., 2014 ).…”

Section: Drug Resistance In Leishmanial Parasitementioning

confidence: 99%

The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective

Kamran

Bhattacharjee²,

Das³

et al. 2023

Front. Cell. Infect. Microbiol.

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Leishmania is an intracellular, zoonotic, kinetoplastid eukaryote with more than 1.2 million cases all over the world. The leishmanial chromosomes are divided into polymorphic chromosomal ends, conserved central domains, and antigen-encoding genes found in telomere-proximal regions. The genome flexibility of chromosomal ends of the leishmanial parasite is known to cause drug resistance and intracellular survival through the evasion of host defense mechanisms. Therefore, in this review, we discuss the plasticity of Leishmania genome organization which is the primary cause of drug resistance and parasite survival. Moreover, we have not only elucidated the causes of such genome plasticity which includes aneuploidy, epigenetic factors, copy number variation (CNV), and post-translation modification (PTM) but also highlighted their impact on drug resistance and parasite survival.

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A Guide to Next Generation Sequence Analysis of Leishmania Genomes

Cited by 7 publications

References 46 publications

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Laboratory diagnostics for human Leishmania infections: a polymerase chain reaction-focussed review of detection and identification methods

The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective

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