In vitro sensitivity of Plasmodium falciparum from China-Myanmar border area to major ACT drugs and polymorphisms in potential target genes.
Drug resistance has always been one of the most important impediments to global malaria control. Artemisinin resistance has recently been confirmed in the Greater Mekong Subregion (GMS) and efforts for surveillance and containment are intensified. To determine potential mechanisms of artemisinin res...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3365119?pdf=render |
| _version_ | 1818451081125953536 |
|---|---|
| author | Zenglei Wang Daniel Parker Hao Meng Lanou Wu Jia Li Zhen Zhao Rongping Zhang Miao Miao Qi Fan Haiyan Wang Liwang Cui Zhaoqing Yang |
| author_facet | Zenglei Wang Daniel Parker Hao Meng Lanou Wu Jia Li Zhen Zhao Rongping Zhang Miao Miao Qi Fan Haiyan Wang Liwang Cui Zhaoqing Yang |
| author_sort | Zenglei Wang |
| collection | DOAJ |
| description | Drug resistance has always been one of the most important impediments to global malaria control. Artemisinin resistance has recently been confirmed in the Greater Mekong Subregion (GMS) and efforts for surveillance and containment are intensified. To determine potential mechanisms of artemisinin resistance and monitor the emergence and spread of resistance in other regions of the GMS, we investigated the in vitro sensitivity of 51 culture-adapted parasite isolates from the China-Myanmar border area to four drugs. The 50% inhibitory concentrations (IC₅₀s) of dihydroartemisinin, mefloquine and lumefantrine were clustered in a relatively narrow, 3- to 6-fold range, whereas the IC₅₀ range of artesunate was 12-fold. We assessed the polymorphisms of candidate resistance genes pfcrt, pfmdr1, pfATP6, pfmdr6 and pfMT (a putative metabolite/drug transporter). The K76T mutation in pfcrt reached fixation in the study parasite population, whereas point mutations in pfmdr1 and pfATP6 had low levels of prevalence. In addition, pfmdr1 gene amplification was not detected. None of the mutations in pfmdr1 and pfATP6 was associated significantly with in vitro sensitivity to artemisinin derivatives. The ABC transporter gene pfmdr6 harbored two point mutations, two indels, and number variations in three simple repeats. Only the length variation in a microsatellite repeat appeared associated with altered sensitivity to dihydroartemisinin. The PfMT gene had two point mutations and one codon deletion; the I30N and N496- both reached high levels of prevalence. However, none of the SNPs or haplotypes in PfMT were correlated significantly with resistance to the four tested drugs. Compared with other parasite populations from the GMS, our studies revealed drastically different genotype and drug sensitivity profiles in parasites from the China-Myanmar border area, where artemisinins have been deployed extensively for over 30 years. |
| first_indexed | 2024-12-14T21:01:31Z |
| format | Article |
| id | doaj.art-e98cc18687d14a16a9b2abf28706a47d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T21:01:31Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e98cc18687d14a16a9b2abf28706a47d2022-12-21T22:47:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3092710.1371/journal.pone.0030927In vitro sensitivity of Plasmodium falciparum from China-Myanmar border area to major ACT drugs and polymorphisms in potential target genes.Zenglei WangDaniel ParkerHao MengLanou WuJia LiZhen ZhaoRongping ZhangMiao MiaoQi FanHaiyan WangLiwang CuiZhaoqing YangDrug resistance has always been one of the most important impediments to global malaria control. Artemisinin resistance has recently been confirmed in the Greater Mekong Subregion (GMS) and efforts for surveillance and containment are intensified. To determine potential mechanisms of artemisinin resistance and monitor the emergence and spread of resistance in other regions of the GMS, we investigated the in vitro sensitivity of 51 culture-adapted parasite isolates from the China-Myanmar border area to four drugs. The 50% inhibitory concentrations (IC₅₀s) of dihydroartemisinin, mefloquine and lumefantrine were clustered in a relatively narrow, 3- to 6-fold range, whereas the IC₅₀ range of artesunate was 12-fold. We assessed the polymorphisms of candidate resistance genes pfcrt, pfmdr1, pfATP6, pfmdr6 and pfMT (a putative metabolite/drug transporter). The K76T mutation in pfcrt reached fixation in the study parasite population, whereas point mutations in pfmdr1 and pfATP6 had low levels of prevalence. In addition, pfmdr1 gene amplification was not detected. None of the mutations in pfmdr1 and pfATP6 was associated significantly with in vitro sensitivity to artemisinin derivatives. The ABC transporter gene pfmdr6 harbored two point mutations, two indels, and number variations in three simple repeats. Only the length variation in a microsatellite repeat appeared associated with altered sensitivity to dihydroartemisinin. The PfMT gene had two point mutations and one codon deletion; the I30N and N496- both reached high levels of prevalence. However, none of the SNPs or haplotypes in PfMT were correlated significantly with resistance to the four tested drugs. Compared with other parasite populations from the GMS, our studies revealed drastically different genotype and drug sensitivity profiles in parasites from the China-Myanmar border area, where artemisinins have been deployed extensively for over 30 years.http://europepmc.org/articles/PMC3365119?pdf=render |
| spellingShingle | Zenglei Wang Daniel Parker Hao Meng Lanou Wu Jia Li Zhen Zhao Rongping Zhang Miao Miao Qi Fan Haiyan Wang Liwang Cui Zhaoqing Yang In vitro sensitivity of Plasmodium falciparum from China-Myanmar border area to major ACT drugs and polymorphisms in potential target genes. PLoS ONE |
| title | In vitro sensitivity of Plasmodium falciparum from China-Myanmar border area to major ACT drugs and polymorphisms in potential target genes. |
| title_full | In vitro sensitivity of Plasmodium falciparum from China-Myanmar border area to major ACT drugs and polymorphisms in potential target genes. |
| title_fullStr | In vitro sensitivity of Plasmodium falciparum from China-Myanmar border area to major ACT drugs and polymorphisms in potential target genes. |
| title_full_unstemmed | In vitro sensitivity of Plasmodium falciparum from China-Myanmar border area to major ACT drugs and polymorphisms in potential target genes. |
| title_short | In vitro sensitivity of Plasmodium falciparum from China-Myanmar border area to major ACT drugs and polymorphisms in potential target genes. |
| title_sort | in vitro sensitivity of plasmodium falciparum from china myanmar border area to major act drugs and polymorphisms in potential target genes |
| url | http://europepmc.org/articles/PMC3365119?pdf=render |
| work_keys_str_mv | AT zengleiwang invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT danielparker invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT haomeng invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT lanouwu invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT jiali invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT zhenzhao invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT rongpingzhang invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT miaomiao invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT qifan invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT haiyanwang invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT liwangcui invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes AT zhaoqingyang invitrosensitivityofplasmodiumfalciparumfromchinamyanmarborderareatomajoractdrugsandpolymorphismsinpotentialtargetgenes |