Publications by authors named "Shin-Ichiro Tachibana"

25 Publications

  • Page 1 of 1

Fitness of sulfadoxine-resistant Plasmodium berghei harboring a single mutation in dihydropteroate synthase (DHPS).

Acta Trop 2021 Oct 15;222:106049. Epub 2021 Jul 15.

Department of Tropical Medicine and Parasitology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. Electronic address:

Genetic changes conferring drug resistance are generally believed to impose fitness costs to pathogens in the absence of the drug. However, the fitness of resistant parasites against sulfadoxine/pyrimethamine has been inconclusive in Plasmodium falciparum. This is because resistance is conferred by the complex combination of mutations in dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), which makes it difficult to separately assess the extent and magnitude of the costs imposed by mutations in dhps and dhfr. To assess the fitness costs imposed by sulfadoxine resistance alone, we generated a transgenic rodent malaria parasite, P. berghei clone harboring an A394G mutation in dhps (PbDHPS-A394G), corresponding to the causative mutation for sulfadoxine resistance in P. falciparum (PfDHPS-A437G). A four-day suppressive test confirmed that the PbDHPS-A394G clone was resistant to sulfadoxine. PbDHPS-A394G and wild-type clones showed similar growth rates and gametocyte production. This observation was confirmed in competitive experiments in which PbDHPS-A394G and wild-type clones were co-infected into mice to directly assess the survival competition between them. In the mosquitoes, there were no significant differences in oocyst production between PbDHPS-A394G and wild-type. These results indicate that the PbDHPS-A394G mutation alters the parasites to sulfadoxine resistance but may not impose fitness disadvantages during the blood stages in mice and oocyst formation in mosquitoes. These results partly explain the persistence of the PfDHPS-A437G mutant in the natural parasite populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actatropica.2021.106049DOI Listing
October 2021

Isolation of Mutants With Reduced Susceptibility to Piperaquine From a Mutator of the Rodent Malaria Parasite .

Front Cell Infect Microbiol 2021 16;11:672691. Epub 2021 Jun 16.

Department of Tropical Medicine and Parasitology, Faculty of Medicine, Juntendo University, Tokyo, Japan.

Elucidation of the mechanisms of drug resistance in malaria parasites is crucial for combatting the emergence and spread of resistant parasites, which can be achieved by tracing resistance-associated mutations and providing useful information for drug development. Previously, we produced a novel genetic tool, a mutator (PbMut), whose base substitution rate is 36.5 times higher than that of wild-type parasites. Here, we report the isolation of a mutant with reduced susceptibility to piperaquine (PPQ) from PbMut under PPQ pressure by sequential nine-cycle screening and named it PbMut-PPQ-R-P9. The ED of PbMut-PPQ-R-P9 was 1.79 times higher than that of wild-type parasites, suggesting that its PPQ resistance is weak. In the 1 screen, recrudescence occurred in the mice infected with PbMut but not in those infected with wild-type parasites, suggesting earlier emergence of PPQ-resistant parasites from PbMut. Whole-genome sequence analysis of PbMut-PPQ-R-P9 clones revealed that eight nonsynonymous mutations were conserved in all clones, including N331I in , the gene encoding chloroquine resistance transporter (). The PbCRT(N331I) mutation already existed in the parasite population after the 2 screen and was predominant in the population after the 8 screen. An artificially inserted PbCRT(N331I) mutation gave rise to reduced PPQ susceptibility in genome-edited parasites (PbCRT-N331I). The PPQ susceptibility and growth rates of PbCRT-N331I parasites were significantly lower than those of PbMut-PPQ-R-P9, implying that additional mutations in the PbMut-PPQ-R9 parasites could compensate for the fitness cost of the PbCRT(N331I) mutation and contribute to reduced PPQ susceptibility. In summary, PbMut could serve as a novel genetic tool for predicting gene mutations responsible for drug resistance. Further study on PbMut-PPQ-R-P9 could identify genetic changes that compensate for fitness costs owing to drug resistance acquisition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.672691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242943PMC
July 2021

Development of a rapid scabies immunodiagnostic assay based on transcriptomic analysis of Sarcoptes scabiei var. nyctereutis.

Sci Rep 2021 03 19;11(1):6455. Epub 2021 Mar 19.

Department of Microbiology and Immunology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.

Scabies is a highly contagious skin disease caused by the mite Sarcoptes scabiei that affects many mammals. However, the sensitivity of traditional tests for scabies diagnosis in humans is less than 50%. To simplify the diagnosis of scabies, methods that are simple, sensitive, specific, and cost-effective are required. We developed an immunodiagnostic test based on S. scabiei var. nyctereutis RNA-seq data collected from Japanese raccoon dogs with sarcoptic mange. Three candidate antigens-a highly expressed hypothetical protein "QR98_0091190," another mite allergen known as "SMIPP-Cc," and an abundant "vitellogenin-like protein"-were evaluated by western-blot analysis. A lateral flow immunoassay, using specific antibodies against the vitellogenin-like protein, successfully detected scabies in the skin flakes of S. scabiei-infected raccoon dogs. This assay can potentially diagnose scabies more accurately in wildlife, as well as in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85290-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979781PMC
March 2021

Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in Northern Uganda.

Parasitol Int 2021 Apr 25;81:102277. Epub 2020 Dec 25.

Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address:

In Uganda, artemether-lumefantrine was introduced as an artemisinin-based combination therapy (ACT) for malaria in 2006. We have previously reported a moderate decrease in ex vivo efficacy of lumefantrine in Northern Uganda, where we also detected ex vivo artemisinin-resistant Plasmodium falciparum. Therefore, it is necessary to search for candidate partner alternatives for ACT. Here, we investigated ex vivo susceptibility to four ACT partner drugs as well as quinine and chloroquine, in 321 cases between 2013 and 2018. Drug-resistant mutations in pfcrt and pfmdr1 were also determined. Ex vivo susceptibility to amodiaquine, quinine, and chloroquine was well preserved, whereas resistance to mefloquine was found in 45.8%. There were few cases of multi-drug resistance. Reduced sensitivity to mefloquine and lumefantrine was significantly associated with the pfcrt K76 wild-type allele, in contrast to the association between chloroquine resistance and the K76T allele. Pfmdr1 duplication was not detected in any of the cases. Amodiaquine, a widely used partner drug for ACT in African countries, may be the first promising alternative in case lumefantrine resistance emerges. Therapeutic use of mefloquine may not be recommended in this area. This study also emphasizes the need for sustained monitoring of antimalarial susceptibility in Northern Uganda to develop proper treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parint.2020.102277DOI Listing
April 2021

Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea.

PLoS Pathog 2020 12 15;16(12):e1009133. Epub 2020 Dec 15.

Department of Tropical Medicine and Parasitology, Juntendo University Faculty of Medicine, Tokyo, Japan.

The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants' genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites' drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1009133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771869PMC
December 2020

Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda.

Malar J 2020 Feb 18;19(1):76. Epub 2020 Feb 18.

Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Background: Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods.

Methods: Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed.

Results: Chloroquine resistance (≥ 100 nM) was observed in only 3 (1.3%) samples. Average IC values for chloroquine were persistently low throughout the study period (17.4-24.9 nM). Parasites harbouring pfcrt K76 alleles showed significantly lower ICs to chloroquine than the parasites harbouring K76T alleles (21.4 nM vs. 43.1 nM, p-value = 3.9 × 10). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018.

Conclusion: This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12936-020-03157-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026951PMC
February 2020

The Autophagy-Related Protein GABARAP Is Induced during Overwintering in the Bean Bug (Hemiptera: Alydidae).

J Econ Entomol 2020 02;113(1):427-434

Department of Biology and Geosciences, Graduate School of Science, Osaka City University, Osaka, Japan.

In most insects dependent on food resources that deplete seasonally, mechanisms exist to protect against starvation. Insects overcome periods of food depletion using diapause-associated physiological mechanisms, such as increased energy resources in fat bodies and suppression of metabolism. Because autophagy supplies energy resources through the degradation of intracellular components, we hypothesized that it might be an additional strategy to combat starvation during overwintering. In this study, we measured the abundance of the proteins involved in the signaling pathway of autophagy during overwintering in adults of the bean bug Riptortus pedestris (Fabricius) (Hemiptera: Alydidae), which must withstand the periodic depletion of its host plants from late fall to early spring. Although the levels of gamma-aminobutyric acid receptor-associated protein (GABARAP) markedly increased after the cessation of food supply, AMP-activated protein kinase (AMPK) and target of rapamycin (TOR) were not found to be associated with food depletion. Thus, food depletion appears to induce autophagy independent of AMPK and TOR. The GABARAP levels significantly increased universally when the food supply ceased, irrespective of the diapause status of adults and low-temperature conditions. In overwintering diapause adults under seminatural conditions, the GABARAP levels significantly increased during early spring. Thus, autophagy appears to assist the survival of the bean bugs under natural conditions of food deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jee/toz287DOI Listing
February 2020

Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea.

Malar J 2018 Nov 26;17(1):434. Epub 2018 Nov 26.

Department of Tropical Medicine and Parasitology, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: Chloroquine treatment for Plasmodium falciparum has been discontinued in almost all endemic regions due to the spread of resistant isolates. Reversal of chloroquine susceptibility after chloroquine discontinuation has been reported in dozens of endemic regions. However, this phenomenon has been mostly observed in Africa and is not well documented in other malaria endemic regions. To investigate this, an ex vivo study on susceptibility to chloroquine and lumefantrine was conducted during 2016-2018 in Wewak, Papua New Guinea where chloroquine had been removed from the official malaria treatment regimen in 2010. Genotyping of pfcrt and pfmdr1 was also performed.

Results: In total, 368 patients were enrolled in this study. Average IC values for chloroquine were 106.6, 80.5, and 87.6 nM in 2016, 2017, and 2018, respectively. These values were not significantly changed from those obtained in 2002/2003 (108 nM). The majority of parasites harboured a pfcrt K76T the mutation responsible for chloroquine resistance. However, a significant upward trend was observed in the frequency of the K76 (wild) allele from 2.3% in 2016 to 11.7% in 2018 (P = 0.008; Cochran-Armitage trend test).

Conclusions: Eight years of chloroquine withdrawal has not induced a significant recovery of susceptibility in Papua New Guinea. However, an increasing tendency of parasites harbouring chloroquine-susceptible K76 suggests a possibility of resurgence of chloroquine susceptibility in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12936-018-2585-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260888PMC
November 2018

Artemisinin-Resistant Plasmodium falciparum with High Survival Rates, Uganda, 2014-2016.

Emerg Infect Dis 2018 04;24(4):718-726

Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014-2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage-specific P. falciparum susceptibility to artemisinin. We conducted 4 cross-sectional surveys to assess artemisinin sensitivity in Gulu, Uganda. Among 194 isolates, survival rates (ratio of viable drug-exposed parasites to drug-nonexposed controls) were high (>10%) for 4 isolates. Similar rates have been closely associated with delayed parasite clearance after drug treatment and are considered to be a proxy for the artemisinin-resistant phenotype. Of these, the PfKelch13 mutation was observed in only 1 isolate, A675V. Population genetics analysis suggested that these possibly artemisinin-resistant isolates originated in Africa. Large-scale surveillance of possibly artemisinin-resistant parasites in Africa would provide useful information about treatment outcomes and help regional malaria control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2404.170141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875287PMC
April 2018

Absence of in vivo selection for K13 mutations after artemether-lumefantrine treatment in Uganda.

Malar J 2017 01 9;16(1):23. Epub 2017 Jan 9.

Division of Malaria Research, Proteo-Science Center, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime, 790-8577, Japan.

Background: Individual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether-lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein.

Methods: Artemether-lumefantrine efficacy study with a follow-up period of 28 days was conducted in northern Uganda in 2014. The above-mentioned genotypes were comparatively analysed before drug administration and on days; 3, 7, and 28 days after treatment.

Results: In 61 individuals with successful follow-up, artemether-lumefantrine treatment regimen was very effective with PCR adjusted efficacy of 95.2%. Among 146 isolates obtained before treatment, wild-type alleles were observed in 98.6% of isolates in pfkelch13 and in all isolates in the six putative background genes except I356T in pfcrt, which had 2.4% of isolates as mixed infections. In vivo selection study revealed that all isolates detected in the follow-up period harboured wild type alleles in pfkelch13 and the six background genes.

Conclusion: Mutations in pfkelch13 and the six background genes may not play an important role in the in vivo selection after artemether-lumefantrine treatment in Uganda. Different mechanisms might rather be associated with the existence of parasites after treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12936-016-1663-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223472PMC
January 2017

Plasmodium falciparum kelch 13: a potential molecular marker for tackling artemisinin-resistant malaria parasites.

Expert Rev Anti Infect Ther 2016 4;14(1):125-35. Epub 2015 Nov 4.

a Department of Molecular and Cellular Parasitology , Juntendo University School of Medicine , Tokyo , Japan.

Although artemisinin combination therapies have been deployed as a first-line treatment for uncomplicated malaria in almost all endemic countries, artemisinin-resistant parasites have emerged and have gradually spread across the Greater Mekong subregions. There is growing concern that the resistant parasites may migrate to or emerge indigenously in sub-Saharan Africa, which might provoke a global increase in malaria-associated morbidity and mortality. Therefore, development of molecular markers that enable identification of artemisinin resistance with high sensitivity is urgently required to combat this issue. In 2014, a potential artemisinin-resistance responsible gene, Plasmodium falciparum kelch13, was discovered. Here, we review the genetic features of P. falciparum kelch13 and discuss its related resistant mechanisms and potential as a molecular marker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1586/14787210.2016.1106938DOI Listing
October 2016

Modification of Male Courtship Motivation by Olfactory Habituation via the GABAA Receptor in Drosophila melanogaster.

PLoS One 2015 7;10(8):e0135186. Epub 2015 Aug 7.

Career-Path Promotion Unit for Young Life Scientists, Kyoto University, Kyoto, 606-8501, Japan; Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan; ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo, 113-8657, Japan.

A male-specific component, 11-cis-vaccenyl acetate (cVA) works as an anti-aphrodisiac pheromone in Drosophila melanogaster. The presence of cVA on a male suppresses the courtship motivation of other males and contributes to suppression of male-male homosexual courtship, while the absence of cVA on a female stimulates the sexual motivation of nearby males and enhances the male-female interaction. However, little is known how a male distinguishes the presence or absence of cVA on a target fly from either self-produced cVA or secondhand cVA from other males in the vicinity. In this study, we demonstrate that male flies have keen sensitivity to cVA; therefore, the presence of another male in the area reduces courtship toward a female. This reduced level of sexual motivation, however, could be overcome by pretest odor exposure via olfactory habituation to cVA. Real-time imaging of cVA-responsive sensory neurons using the neural activity sensor revealed that prolonged exposure to cVA decreased the levels of cVA responses in the primary olfactory center. Pharmacological and genetic screening revealed that signal transduction via GABAA receptors contributed to this olfactory habituation. We also found that the habituation experience increased the copulation success of wild-type males in a group. In contrast, transgenic males, in which GABA input in a small subset of local neurons was blocked by RNAi, failed to acquire the sexual advantage conferred by habituation. Thus, we illustrate a novel phenomenon in which olfactory habituation positively affects sexual capability in a competitive environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135186PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529276PMC
May 2016

Plasmodium vivax and Plasmodium falciparum at the crossroads of exchange among islands in Vanuatu: implications for malaria elimination strategies.

PLoS One 2015 20;10(3):e0119475. Epub 2015 Mar 20.

Island Malaria Group, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Parasitology, Graduate School of Medicine, Osaka City University, Osaka, Japan; Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Understanding the transmission and movement of Plasmodium parasites is crucial for malaria elimination and prevention of resurgence. Located at the limit of malaria transmission in the Pacific, Vanuatu is an ideal candidate for elimination programs due to low endemicity and the isolated nature of its island setting. We analyzed the variation in the merozoite surface protein 1 (msp1) and the circumsporozoite protein (csp) of P. falciparum and P. vivax populations to examine the patterns of gene flow and population structures among seven sites on five islands in Vanuatu. Genetic diversity was in general higher in P. vivax than P. falciparum from the same site. In P. vivax, high genetic diversity was likely maintained by greater extent of gene flow among sites and among islands. Consistent with the different patterns of gene flow, the proportion of genetic variance found among islands was substantially higher in P. falciparum (28.81-31.23%) than in P. vivax (-0.53-3.99%). Our data suggest that the current island-by-island malaria elimination strategy in Vanuatu, while adequate for P. falciparum elimination, might need to be complemented with more centrally integrated measures to control P. vivax movement across islands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119475PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368729PMC
February 2016

Contrasting infection susceptibility of the Japanese macaques and cynomolgus macaques to closely related malaria parasites, Plasmodium vivax and Plasmodium cynomolgi.

Parasitol Int 2015 Jun 12;64(3):274-81. Epub 2014 Oct 12.

Laboratory of Malariology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.

Although the human malaria parasite Plasmodium vivax is closely related to Asian Old World monkey malaria parasites, there are no reports of P. vivax infections in macaques. In this study, we compared the infectivity of P. vivax and Plasmodium cynomolgi in Japanese macaques (Macaca fuscata) and in cynomolgus macaques (Macaca fascicularis). The Japanese macaques were highly susceptible to P. cynomolgi but not to P. vivax, whereas cynomolgus macaques showed mild/limited P. cynomolgi infection and were, also, not susceptible to P. vivax. Serotyping and amino acid sequence comparison of erythrocyte surface Duffy antigen/receptor for chemokines (DARC) indicate that the Japanese macaque DARC sequence is nearly identical to that of rhesus (Macaca mulatta) and cynomolgus macaques. This suggests that the macaques share a common mechanism for preventing P. vivax infection. Comparison of amino acid sequences of the Duffy-binding-like (DBL) domain from several different Plasmodium species suggests that P. vivax DBLs will not bind to macaque DARCs, which can explain the lack of P. vivax infectivity. The DBL sequence analyses also suggest that P. cynomolgi DBLs may target Japanese macaque erythrocytes through a DARC-independent interaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parint.2014.10.004DOI Listing
June 2015

Characteristic age distribution of Plasmodium vivax infections after malaria elimination on Aneityum Island, Vanuatu.

Infect Immun 2014 Jan 28;82(1):243-52. Epub 2013 Oct 28.

Island Malaria Group, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Resurgence is a major concern after malaria elimination. After the initiation of the elimination program on Aneityum Island in 1991, microscopy showed that Plasmodium falciparum disappeared immediately, whereas P. vivax disappeared from 1996 onward, until P. vivax cases were reported in January 2002. By conducting malariometric surveys of the entire population of Aneityum, we investigated the age distribution of individuals with parasites during this epidemic in the context of antimalarial antibody levels and parasite antigen diversity. In July 2002, P. vivax infections were detected by microscopy in 22/759 individuals: 20/298 born after the beginning of the elimination program in 1991, 2/126 born between 1982 and 1991, and none of 335 born before 1982. PCR increased the number of infections detected to 77, distributed among all age groups. Prevalences were 12.1%, 16.7%, and 6.0%, respectively (P < 0.001). In November, a similar age pattern was found, but with fewer infections: 6/746 and 39/741 individuals were found to be infected by microscopy and PCR, respectively. The frequencies of antibody responses to P. vivax were significantly higher in individuals born before 1991 than in younger age groups and were similar to those on Malakula Island, an area of endemicity. Remarkably low antigen diversity (h, 0.15) of P. vivax infections was observed on Aneityum compared with the other islands (h, 0.89 to 1.0). A P. vivax resurgence was observed among children and teenagers on Aneityum, an age distribution similar to those before elimination and on islands where P. vivax is endemic, suggesting that in the absence of significant exposure, immunity may persist, limiting infection levels in adults. The limited parasite gene pool on islands may contribute to this protection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/IAI.00931-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911855PMC
January 2014

Plasmodium falciparum mitochondrial genetic diversity exhibits isolation-by-distance patterns supporting a sub-Saharan African origin.

Mitochondrion 2013 Nov 1;13(6):630-6. Epub 2013 Sep 1.

Laboratory of Malariology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.

The geographical distribution of single nucleotide polymorphism (SNP) in the mitochondrial genome of the human malaria parasite Plasmodium falciparum was investigated. We identified 88 SNPs in 516 isolates from seven parasite populations in Africa, Southeast Asia and Oceania. Analysis of the SNPs postulated a sub-Saharan African origin and recovered a strong negative correlation between within-population SNP diversity and geographic distance from the putative African origin over Southeast Asia and Oceania. These results are consistent with those previously obtained for nuclear genome-encoded housekeeping genes, indicating that the pattern of inheritance does not substantially affect the geographical distribution of SNPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mito.2013.08.008DOI Listing
November 2013

Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade.

Nat Genet 2012 Sep 5;44(9):1051-5. Epub 2012 Aug 5.

Laboratory of Malariology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.

P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon of P. vivax, the most prevalent malaria-causing species in humans outside of Africa. Because P. cynomolgi shares many phenotypic, biological and genetic characteristics with P. vivax, we generated draft genome sequences for three P. cynomolgi strains and performed genomic analysis comparing them with the P. vivax genome, as well as with the genome of a third previously sequenced simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey malaria clade can be characterized by copy-number variants (CNVs) in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P. cynomolgi genome, providing a map of genetic variation that can be used to map parasite traits and study parasite populations. The sequencing of the P. cynomolgi genome is a critical step in developing a model system for P. vivax research and in counteracting the neglect of P. vivax.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.2375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759362PMC
September 2012

Age of the last common ancestor of extant Plasmodium parasite lineages.

Gene 2012 Jul 25;502(1):36-9. Epub 2012 Apr 25.

Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

Parasites of the genus Plasmodium infect all classes of amniotes (mammals, birds and reptiles) and display host specificity in their infections. It is therefore generally believed that Plasmodium parasites co-evolved intimately with their hosts. Here, we report that based on an evolutionary analysis using 22 genes in the nuclear genome, extant lineages of Plasmodium parasites originated roughly in the Oligocene epoch after the emergence of their hosts. This timing on the age of the common ancestor of extant Plasmodium parasites suggest the importance of host switches and lends support to the evolutionary scenario of a "malaria big bang" that was proposed based on the evolutionary analysis using the mitochondrial genome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2012.04.037DOI Listing
July 2012

Worldwide sequence conservation of transmission-blocking vaccine candidate Pvs230 in Plasmodium vivax.

Vaccine 2011 Jun 21;29(26):4308-15. Epub 2011 Apr 21.

Cell-free Science and Technology Research Center, Ehime University, Matsuyama, Ehime 790-8577, Japan.

Pfs230, surface protein of gametocyte/gamete of the human malaria parasite, Plasmodium falciparum, is a prime candidate of malaria transmission-blocking vaccine. Plasmodium vivax has an ortholog of Pfs230 (Pvs230), however, there has been no study in any aspects on Pvs230 to date. To investigate whether Pvs230 can be a vivax malaria transmission-blocking vaccine, we performed evolutionary and population genetic analysis of the Pvs230 gene (pvs230: PVX_003905). Our analysis of Pvs230 and its orthologs in eight Plasmodium species revealed two distinctive parts: an interspecies variable part (IVP) containing species-specific oligopeptide repeats at the N-terminus and a 7.5kb interspecies conserved part (ICP) containing 14 cysteine-rich domains. Pvs230 was closely related to its orthologs, Pks230 and Pcys230, in monkey malaria parasites. Analysis of 113 pvs230 sequences obtained from worldwide, showed that nucleotide diversity is remarkably low in the non-repeat 8-kb region of pvs230 (θπ=0.00118) with 77 polymorphic nucleotide sites, 40 of which results in amino acid replacements. A signature of purifying selection but not of balancing selection was seen on pvs230. Functional and/or structural constraints may limit the level of polymorphism in pvs230. The observed limited polymorphism in pvs230 should ground for utilization of Pvs230 as an effective transmission-blocking vaccine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2011.04.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130600PMC
June 2011

Limited polymorphism of the Plasmodium vivax merozoite surface protein 1 gene in isolates from Turkey.

Am J Trop Med Hyg 2010 Dec;83(6):1230-7

Department of Microbiology, Harran University Medical Faculty, Sanliurfa, Turkey.

The 200-kD merozoite surface protein of Plasmodium vivax (PvMSP-1) is one of the leading vaccine candidates against P. vivax malaria. However, the gene encoding PvMSP-1 (pvmsp1) is highly polymorphic and is a major obstacle to effective vaccine development. To further understand polymorphism in pvmsp1, we obtained 30 full-length pvmsp1 sequences from southeastern Turkey. Comparative analysis of sequences from Turkey and other areas showed substantially limited polymorphism. Substitutions were found at 280 and 162 amino acid sites in samples from other regions and those from Turkey, respectively. Eight substitutions were unique to Turkey. In one of them, D/E at position 1706 in the C-terminal 19-kD region, the K/E change at 1709 was the only polymorphism previously known. Limited diversity was also observed in microsatellites. Data suggest a recent population bottleneck in Turkey that may have obscured a signature for balancing selection in the C-terminal 42-kD region, which was otherwise detectable in other areas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.2010.10-0353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990036PMC
December 2010

Concatenated mitochondrial DNA of the coccidian parasite Eimeria tenella.

Mitochondrion 2011 Mar 31;11(2):273-8. Epub 2010 Oct 31.

International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

Apicomplexan parasites of the genus Plasmodium, pathogens causing malaria, and the genera Babesia and Theileria, aetiological agents of piroplasmosis, are closely related. However, their mitochondrial (mt) genome structures are highly divergent: Plasmodium has a concatemer of 6-kb unit and Babesia/Theileria a monomer of 6.6- to 8.2-kb with terminal inverted repeats. Fragmentation of ribosomal RNA (rRNA) genes and gene arrangements are remarkably distinctive. To elucidate the evolutionary origin of this structural divergence, we determined the mt genome of Eimeria tenella, pathogens of coccidiosis in domestic fowls. Analysis revealed that E. tenella mt genome was concatemeric with similar protein-coding genes and rRNA gene fragments to Plasmodium. Copy number was 50-fold of the nuclear genome. Evolution of structural divergence in the apicomplexan mt genomes is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mito.2010.10.003DOI Listing
March 2011

Regulation of gonad development and respiratory metabolism associated with food availability and reproductive diapause in the rice bug Leptocorisa chinensis.

J Insect Physiol 2008 Feb 21;54(2):445-53. Epub 2007 Nov 21.

National Agricultural Research Center (NARC), Tsukuba, Ibaraki, Japan.

Food has an influence on many life history traits related to dormancy in insects. In our previous study with the rice bug Leptocorisa chinensis (Dallas) (Hemiptera: Alydidae), diapausing females transferred to conditions physically favorable for promoting the gonad development required food intake to resume gonad development, whereas males did not. These differences in response to food between males and females lead to two questions: (1) Was diapause in the starved females completed? (2) Were the starved males that resumed gonad development at the same physiological status as fed males? We tested these questions with two physiological indicators: gonad status and respiratory rate. Results indicate that starved females are able to complete diapause, but show depressed respiration relative to well-fed insects in diapause. Similar to females, starved males that resumed postdiapause gonad development also had depressed respiratory rate, and hence physiological status is presumed to be different between starved and fed individuals. In this study, it was also found that the photoperiodic signal is storable, whereas the food signal acts directly. The adaptive significance of regulation of gonad development and respiratory metabolism in relation to phenology of suitable host plant and reproductive strategy is discussed in both sexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinsphys.2007.11.003DOI Listing
February 2008

Sexual differences in the crucial environmental factors for the timing of postdiapause development in the rice bug Leptocorisa chinensis.

J Insect Physiol 2007 Oct 18;53(10):1000-7. Epub 2007 May 18.

National Agricultural Research Center (NARC), 3-1-1 Kannondai, Tsukuba, Ibaraki, Japan.

Although the regulation of reproductive diapause by environmental factors has been extensively studied in a variety of insect orders, sexual differences in the regulation of diapause are still poorly understood. We examined the effects of environmental factors including photoperiod, temperature and food on the regulation of reproductive diapause in both sexes of the rice bug Leptocorisa chinensis (Dallas) (Hemiptera: Alydidae) in the laboratory and under natural conditions. There was no significant difference in critical daylength (CDL) for diapause induction between the sexes. The CDL corresponded to the daylength in which development of the gonads was suppressed in half the insects caught in the field. Both sexes enter diapause at the same time in successive seasons. In diapause insects, on the other hand, there were sexual differences not only in retention of responsiveness to photoperiod and temperature but also in the food requirement, and these sexual differences lead to different timing of the resumption of reproductive development after overwintering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinsphys.2007.05.004DOI Listing
October 2007

Gene expression of heat-shock proteins (Hsp23, Hsp70 and Hsp90) during and after larval diapause in the blow fly Lucilia sericata.

J Insect Physiol 2005 Jun 22;51(6):641-7. Epub 2005 Jan 22.

Department of Bio- and Geosciences, Graduate School of Science, Osaka City University, Sumiyoshi, Osaka 558-8585, Japan.

Genes encoding heat-shock protein 23 (Hsp23), Hsp70 and Hsp90 were cloned from Lucilia sericata to examine whether their expression is related to the regulation of its larval diapause. The level of all three Hsps mRNAs was consistently low irrespective of diapause status. These results indicate that expression of Hsp23, Hsp70 and Hsp90 is not regulated in response to diapause, in contrast to the flesh fly Sarcophaga crassipalpis that shows upregulation of Hsp23 and Hsp70 and downregulation of Hsp90 during its pupal diapause. On the other hand, Hsp90 transcripts were regulated developmentally in nondiapause larvae of L. sericata, i.e., they were at low levels after cessation of feeding but were considerably upregulated a day before pupariation, suggesting that Hsp90 is involved in a developmental process that occurs between the cessation of feeding and pupariation. When diapause larvae were transferred to all of the conditions that terminate diapause and allow postdiapause development, Hsp90 transcripts were promptly upregulated. These results indicate that Hsp90 may serve as an early marker to predict diapause termination in this species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinsphys.2004.11.012DOI Listing
June 2005

Effects of temperature and photoperiod on the termination of larval diapause in Lucilia sericata (Diptera: Calliphoridae).

Zoolog Sci 2004 Feb;21(2):197-202

Department of Bio- and Geosciences, Graduate School of Science, Osaka City University, Japan.

Larvae of the blow fly, Lucilia sericata (Meigen), enter diapause in the third instar after cessation of feeding. The effects of temperature and photoperiod on the termination of diapause were examined. The diapause terminated spontaneously under the diapause-inducing condition of 20 degrees C and LD 12:12, although pupariation was not synchronous. Diapause development proceeded under a low temperature of 7.5 degrees C. Transfer to long-day conditions of LD 16:8 or to a high temperature of 25 degrees C induced prompt and synchronous pupariation. Low temperatures in winter probably play a predominant role in the termination of diapause under natural conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2108/zsj.21.197DOI Listing
February 2004
-->