pfcrt allelic types with two novel amino acid mutations in chloroquine-resistant Plasmodium falciparum isolates from the Philippines

Chen, NH, Kyle, DE, Pasay, C, Fowler, EV, Baker, J, Peters, JM and Cheng, Q (2003) pfcrt allelic types with two novel amino acid mutations in chloroquine-resistant Plasmodium falciparum isolates from the Philippines. Antimicrobial Agents And Chemotherapy, 47 11: 3500-3505. doi:10.1128/AAC.47.11.3500-3505.2003

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Author Chen, NH
Kyle, DE
Pasay, C
Fowler, EV
Baker, J
Peters, JM
Cheng, Q
Title pfcrt allelic types with two novel amino acid mutations in chloroquine-resistant Plasmodium falciparum isolates from the Philippines
Journal name Antimicrobial Agents And Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
Publication date 2003
Sub-type Article (original research)
DOI 10.1128/AAC.47.11.3500-3505.2003
Open Access Status File (Publisher version)
Volume 47
Issue 11
Start page 3500
End page 3505
Total pages 6
Place of publication Washington
Publisher Amer Soc Microbiology
Language eng
Abstract Mutations in the pfcrt and pfmdr1 genes have been associated with chloroquine resistance in Plasmodium falciparum. Ten and five mutations, respectively, have been identified in these genes from chloroquine-resistant parasites worldwide. Mutation patterns in pfcrt revealed that chloroquine resistance evolved independently in southeast Asia, South America, and Papua New Guinea. However, the evolution of chloroquine resistance in the rest of the Pacific region is unclear. In this study, we examined sequence polymorphisms in these genes in isolates from Morong, Philippines, and compared them to known chloroquine resistance sequences. Two novel mutations, A144T and L160Y, were identified outside of the 10 known mutations in pfcrt in Morong isolates. These novel mutations were identified only in parasites with K76T and N326D but without the common A220S mutation found in most chloroquine-resistant isolates. This represents a unique chloroquine resistance allelic type (K76T/A144T/L160Y/N326D) not previously found elsewhere in the world. One Morong isolate also had an additional C72S mutation, whereas only one isolate possessed an allelic type typical of chloroquine resistance in Asia. Parasites with the novel pfcrt allelic types were resistant to chloroquine in vitro and were unresponsive to verapamil (0.9 muM) chemosensitization, similar to chloroquine-resistant parasites from South America and Papua New Guinea. These results suggest that chloroquine resistance evolved independently in the Philippines and represents a second chloroquine resistance founder event in the South Pacific.
Keyword Microbiology
Pharmacology & Pharmacy
Genetic Diversity
In-vivo
Malaria
Parasites
Polymorphisms
Protein
Marker
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Wed, 17 Oct 2007, 12:24:02 EST