Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factors
The emergence of drug resistance to frontline treatments such as Artemisinin-based combination therapy (ACT) is a major obstacle to the control and eradication of malaria. This problem is compounded by the inherent genetic variability of the parasites, as many established markers of resistance do no...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320723000180 |
| _version_ | 1797771579501838336 |
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| author | Deepak Choubey Bhagyashree Deshmukh Anjani Gopal Rao Abhishek Kanyal Amiya Kumar Hati Somenath Roy Krishanpal Karmodiya |
| author_facet | Deepak Choubey Bhagyashree Deshmukh Anjani Gopal Rao Abhishek Kanyal Amiya Kumar Hati Somenath Roy Krishanpal Karmodiya |
| author_sort | Deepak Choubey |
| collection | DOAJ |
| description | The emergence of drug resistance to frontline treatments such as Artemisinin-based combination therapy (ACT) is a major obstacle to the control and eradication of malaria. This problem is compounded by the inherent genetic variability of the parasites, as many established markers of resistance do not accurately predict the drug-resistant status. There have been reports of declining effectiveness of ACT in the West Bengal and Northeast regions of India, which have traditionally been areas of drug resistance emergence in the country. Monitoring the genetic makeup of a population can help to identify the potential for drug resistance markers associated with it and evaluate the effectiveness of interventions aimed at reducing the spread of malaria. In this study, we performed whole genome sequencing of 53 isolates of Plasmodium falciparum from West Bengal and compared their genetic makeup to isolates from Southeast Asia (SEA) and Africa. We found that the Indian isolates had a distinct genetic makeup compared to those from SEA and Africa, and were more similar to African isolates, with a high prevalence of mutations associated with antigenic variation genes. The Indian isolates also showed a high prevalence of markers of chloroquine resistance (mutations in Pfcrt) and multidrug resistance (mutations in Pfmdr1), but no known mutations associated with artemisinin resistance in the PfKelch13 gene. Interestingly, we observed a novel L152V mutation in PfKelch13 gene and other novel mutations in genes involved in ubiquitination and vesicular transport that have been reported to support artemisinin resistance in the early stages of ACT resistance in the absence of PfKelch13 polymorphisms. Thus, our study highlights the importance of region-specific genomic surveillance for artemisinin resistance and the need for continued monitoring of resistance to artemisinin and its partner drugs. |
| first_indexed | 2024-03-12T21:39:38Z |
| format | Article |
| id | doaj.art-98a7788e27bd4db8ba435e2ccab3bb7f |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-03-12T21:39:38Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-98a7788e27bd4db8ba435e2ccab3bb7f2023-07-27T05:55:49ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072023-08-01225260Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factorsDeepak Choubey0Bhagyashree Deshmukh1Anjani Gopal Rao2Abhishek Kanyal3Amiya Kumar Hati4Somenath Roy5Krishanpal Karmodiya6Department of Technology, Savitribai Phule Pune University, Pune, IndiaDepartment of Biology, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, IndiaDepartment of Biology, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, IndiaDepartment of Biology, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, IndiaDepartment of Medical Entomology, Calcutta School of Tropical Medicine, Kolkata, West Bengal, IndiaDepartment of Human Physiology, Vidyasagar University, Paschim Medinipur, West Bengal, IndiaDepartment of Biology, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411008, Maharashtra, India; Corresponding author.The emergence of drug resistance to frontline treatments such as Artemisinin-based combination therapy (ACT) is a major obstacle to the control and eradication of malaria. This problem is compounded by the inherent genetic variability of the parasites, as many established markers of resistance do not accurately predict the drug-resistant status. There have been reports of declining effectiveness of ACT in the West Bengal and Northeast regions of India, which have traditionally been areas of drug resistance emergence in the country. Monitoring the genetic makeup of a population can help to identify the potential for drug resistance markers associated with it and evaluate the effectiveness of interventions aimed at reducing the spread of malaria. In this study, we performed whole genome sequencing of 53 isolates of Plasmodium falciparum from West Bengal and compared their genetic makeup to isolates from Southeast Asia (SEA) and Africa. We found that the Indian isolates had a distinct genetic makeup compared to those from SEA and Africa, and were more similar to African isolates, with a high prevalence of mutations associated with antigenic variation genes. The Indian isolates also showed a high prevalence of markers of chloroquine resistance (mutations in Pfcrt) and multidrug resistance (mutations in Pfmdr1), but no known mutations associated with artemisinin resistance in the PfKelch13 gene. Interestingly, we observed a novel L152V mutation in PfKelch13 gene and other novel mutations in genes involved in ubiquitination and vesicular transport that have been reported to support artemisinin resistance in the early stages of ACT resistance in the absence of PfKelch13 polymorphisms. Thus, our study highlights the importance of region-specific genomic surveillance for artemisinin resistance and the need for continued monitoring of resistance to artemisinin and its partner drugs.http://www.sciencedirect.com/science/article/pii/S2211320723000180MalariaPlasmodium falciparumIndian isolatesArtemisinin resistancePfKelch13 mutationsGenomics |
| spellingShingle | Deepak Choubey Bhagyashree Deshmukh Anjani Gopal Rao Abhishek Kanyal Amiya Kumar Hati Somenath Roy Krishanpal Karmodiya Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factors International Journal for Parasitology: Drugs and Drug Resistance Malaria Plasmodium falciparum Indian isolates Artemisinin resistance PfKelch13 mutations Genomics |
| title | Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factors |
| title_full | Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factors |
| title_fullStr | Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factors |
| title_full_unstemmed | Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factors |
| title_short | Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factors |
| title_sort | genomic analysis of indian isolates of plasmodium falciparum implications for drug resistance and virulence factors |
| topic | Malaria Plasmodium falciparum Indian isolates Artemisinin resistance PfKelch13 mutations Genomics |
| url | http://www.sciencedirect.com/science/article/pii/S2211320723000180 |
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