title: Competition between Plasmodium falciparum strains in clinical infections during in vitro culture adaptation.
abstract: We evaluated the dynamics of parasite populations during in vitro culture adaptation in 15 mixed Plasmodium falciparum infections, which were collected from a hypoendemic area near the China-Myanmar border. Allele types at the msp1 block 2 in the initial clinical samples and during subsequent culture were quantified weekly using a quantitative PCR method. All mixed infections carried two allele types based on the msp1 genotyping result. We also genotyped several polymorphic sites in the dhfr, dhps and mdr1 genes on day 0 and day 28, which showed that most of the common sites analyzed were monomorphic. Two of the three clinical samples mixed at dhps 581 remained stable while one changed to wild-type during the culture. During in vitro culture, we observed a gradual loss of parasite populations with 10 of the 15 mixed infections becoming monoclonal by day 28 based on the msp1 allele type. In most cases, the more abundant msp1 allele types in the clinical blood samples at the beginning of culture became the sole or predominant allele types on day 28. These results suggest that some parasites may have growth advantages and the loss of parasite populations during culture adaptation of mixed infections may lead to biased results when comparing the phenotypes such as drug sensitivity of the culture-adapted parasites.
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Yunnan Province 650500, China.
authors.forename: Kexuan
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Yunnan Province 650500, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Sun
authors.affiliation: Center for Disease Control and Prevention, Yingjiang, Yunnan Province 679300, China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Dalian Institute of Biotechnology, Dalian, Liaoning Province, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Dalian Institute of Biotechnology, Dalian, Liaoning Province, China.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Yunnan Province 650500, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Hao
authors.affiliation: Center for Biomedical Engineering Research, Kunming Medical University, Yunnan Province 650500, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Cell Biology and Genetics, Kunming Medical University, Yunnan Province 650500, China.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Entomology, The Pennsylvania State University, 501 ASI Bldg., University Park, PA 16802, USA. Electronic address: luc2@psu.edu.
authors.forename: Liwang
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Yunnan Province 650500, China. Electronic address: zhaoqingy@yahoo.com.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000483:Alleles; D000953:Antigens, Protozoan / Q000235:genetics; D000962:Antimalarials / Q000627:therapeutic use; D037621:Artemisinins / Q000627:therapeutic use; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000473:pathology; D020066:Merozoite Surface Protein 1 / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics; D011804:Quinolines / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D010879:Piperazines
chemical_list: D000953:Antigens, Protozoan; D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D020066:Merozoite Surface Protein 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D011804:Quinolines; D013762:Tetrahydrofolate Dehydrogenase; C513498:Mdr1 protein, Plasmodium falciparum; C039060:artenimol; C031327:artemisinin; C034759:piperaquine; D010879:Piperazines
keywords: Culture adaptation; Drug resistance; Fitness cost; In vitro competition; Mixed infection; Plasmodium falciparum