Comparative Genomics Facilitates Drug Target Selection and Develops Intervention Strategies Against Leishmania Infection
Leishmaniasis is a global health concern which has no vaccine for its prevention and a limited number of drugs for its treatment. With toxicities, adverse effects and rising incidences of resistance against the anti-leishmanials, there has been a need to
- PDF / 480,657 Bytes
- 19 Pages / 439.37 x 666.142 pts Page_size
- 28 Downloads / 183 Views
Comparative Genomics Facilitates Drug Target Selection and Develops Intervention Strategies Against Leishmania Infections Anindita Paul and Sushma Singh
Abstract
Leishmaniasis is a global health concern which has no vaccine for its prevention and a limited number of drugs for its treatment. With toxicities, adverse effects and rising incidences of resistance against the anti-leishmanials, there has been a need to select drug targets and develop new intervention strategies. The Leishmania Genome Project sequenced the whole genome of Leishmania major Friedlin as the reference strain, later followed by other Leishmania species. It not only unravelled the evolutionary relationships among them, but also highlighted their contrasts at the genetic level. The specific characteristics may be responsible for the distinct disease forms they cause, which has also been observed in various species of Plasmodium and Trypanosoma. Many speciesspecific genes were also identified. Their genomes differ in chromosome number, GC content, gene copy number and pseudogenes as well. Comparing whole genomes has helped in identifying new targets by selecting genes with a putative function. Comparative analysis of the Leishmania genomes has helped in pin pointing the genes which help in parasite survival inside the host and aid in drug resistance by increasing their copy number. Gene such as Amastin, A2 and Glycoprotein GP63 have shown their involvement in the disease pathogenesis using comparative genomics, which can be used to design therapeutic strategies. Keywords
Comparative genomics · Drug target · L. major · L. donovani · Copy number · A2 gene · Amastin
A. Paul · S. Singh (*) Department of Biotechnology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab, India e-mail: [email protected] # Springer Nature Singapore Pte Ltd. 2020 S. Singh (ed.), Metagenomic Systems Biology, https://doi.org/10.1007/978-981-15-8562-3_4
75
76
A. Paul and S. Singh
Abbreviations 6PGDH 6PGL A2 ACT AMA1 CL CVL EST EuPathDB FML G6PDH Gp63 HGP HIV-1 HMGR HTS LGN LGP Mb MCL MPL-TDM MRPED NADPH NGS PFGE PGN R5P RNAi RPI Ru5P SLACS SSG UNDP US FDA VL WHO TDR
6-Phosphogluconate dehydrogenase 6-Phosphogluconolactonase Antigen 2 Artemis Comparison Tool Apical Membrane Antigen 1 Cutaneous leishmaniasis Canine visceral leishmaniasis Expressed sequence tag Eukaryotic Pathogen Database Fucose-Mannose Ligand Glucose-6-phosphate Dehydrogenase Glycoprotein 63 Human Genome Project Human Immunodeficiency Virus-1 3-Hydroxy-3-methylglutaryl-CoA reductase High-throughput screening Leishmania Genome Network Leishmania Genome Project Mega base pairs Mucocutaneous leishmaniasis Monophosphoryl lipid A-trehalose dicorynomycolate Myristoylated alanine-rich C kinase substrate-related protein effector domain Nicotinamide adenine dinucleotide phosphate hydrogen Next-generation sequencing Pulsed-field gel electrophoresis Parasite Genome Network Ribose 5-phosphate RNA interference Ribose-5-phosphate isomerase Ribulose 5-phosphate Spliced leader-associ
Data Loading...
