ALM

Targeting the Wolbachia Cell Division Protein FtsZ as a New Approach for Antifilarial Therapy

Publication Date: November 29, 2011
Journal: PLOS Neglected Tropical Diseases
Authors: Zhiru Li, Amanda L. Garner, Christian Gloeckner, Kim D. Janda, et al
Volume: 5
Issue: 11
Pages: e1411
DOI: https://dx.plos.org/10.1371/journal.pntd.0001411
Publisher URL: http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0001411
PubMed: http://www.ncbi.nlm.nih.gov/pubmed/22140592
PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226453
Europe PMC: http://europepmc.org/abstract/MED/22140592
Web of Science: 000298134000032
Scopus: 82555173782
Mendeley: http://www.mendeley.com/research/targeting-wolbachia-cell-division-protein-ftsz-new-approach-antifilarial-therapy

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{"title"=>"Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy", "type"=>"journal", "authors"=>[{"first_name"=>"Zhiru", "last_name"=>"Li", "scopus_author_id"=>"56075480000"}, {"first_name"=>"Amanda L.", "last_name"=>"Garner", "scopus_author_id"=>"22934020200"}, {"first_name"=>"Christian", "last_name"=>"Gloeckner", "scopus_author_id"=>"57190287825"}, {"first_name"=>"Kim D.", "last_name"=>"Janda", "scopus_author_id"=>"35500092800"}, {"first_name"=>"Clotilde K.", "last_name"=>"Carlow", "scopus_author_id"=>"6603794357"}], "year"=>2011, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"pmid"=>"22140592", "pui"=>"363024968", "issn"=>"19352727", "doi"=>"10.1371/journal.pntd.0001411", "isbn"=>"1935-2727", "scopus"=>"2-s2.0-82555173782", "sgr"=>"82555173782"}, "id"=>"7f3c60d1-123f-3d20-8aab-ac937188085c", "abstract"=>"The use of antibiotics targeting the obligate bacterial endosymbiont Wolbachia of filarial parasites has been validated as an approach for controlling filarial infection in animals and humans. Availability of genomic sequences for the Wolbachia (wBm) present in the human filarial parasite Brugia malayi has enabled genome-wide searching for new potential drug targets. In the present study, we investigated the cell division machinery of wBm and determined that it possesses the essential cell division gene ftsZ which was expressed in all developmental stages of B. malayi examined. FtsZ is a GTPase thereby making the protein an attractive Wolbachia drug target. We described the molecular characterization and catalytic properties of Wolbachia FtsZ. We also demonstrated that the GTPase activity was inhibited by the natural product, berberine, and small molecule inhibitors identified from a high-throughput screen. Furthermore, berberine was also effective in reducing motility and reproduction in B. malayi parasites in vitro. Our results should facilitate the discovery of selective inhibitors of FtsZ as a novel anti-symbiotic approach for controlling filarial infection. NOTE: The nucleotide sequences reported in this paper are available in GenBank™ Data Bank under the accession number wAlB-FtsZ (JN616286).", "link"=>"http://www.mendeley.com/research/targeting-wolbachia-cell-division-protein-ftsz-new-approach-antifilarial-therapy", "reader_count"=>33, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>25, "Chemistry"=>3, "Social Sciences"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>3}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>25}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>2}

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Figshare 10802 Apr 20:47 UTC

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{"files"=>["https://ndownloader.figshare.com/files/708603"], "description"=>"Enzyme activity of wBm-FtsZ (•) and Ec-FtsZ (□) was determined in the presence of 0, 25, 50, 100, 200, 400, 600, 800, and 1000 µM berberine sulfate. The data obtained from triplicate samples are expressed as a mean ± standard deviation.", "links"=>[], "tags"=>["sulfate", "inhibition", "gtpase"], "article_id"=>378963, "categories"=>["Biotechnology", "Biochemistry", "Infectious Diseases", "Pharmacology"], "users"=>["Zhiru Li", "Amanda L. Garner", "Christian Gloeckner", "Kim D. Janda", "Clotilde K. Carlow"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001411.g004", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Berberine_sulfate_inhibition_of_the_GTPase_activity_/378963", "title"=>"Berberine sulfate inhibition of the GTPase activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 11:19:05"}
{"files"=>["https://ndownloader.figshare.com/files/708525"], "description"=>"Panel A, activity was determined indirectly by measuring a decrease in NADH concentration by its absorbance at 340 nm. FtsZ hydrolyzes GTP into GDP and inorganic phosphate. The GDP product is used as a substrate by pyruvate kinase (PK) in the presence of phosphoenol pyruvate (PEP) to yield GTP and pyruvic acid as products. Pyruvic acid is used as a substrate in the presence of NADH by lactate dehydrogenase (LDH) to generate lactate and NAD. The consumption of NADH is proportional to GTPase activity. Panel B, comparison of the GTPase activity of wBm-FtsZ and Ec-FtsZ. A control without enzyme was also included. Activity was indicated by a decrease of NADH measured by absorbance at 340 nm.", "links"=>[], "tags"=>["recombinant"], "article_id"=>378889, "categories"=>["Biotechnology", "Biochemistry", "Infectious Diseases", "Pharmacology"], "users"=>["Zhiru Li", "Amanda L. Garner", "Christian Gloeckner", "Kim D. Janda", "Clotilde K. Carlow"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001411.g003", "stats"=>{"downloads"=>1, "page_views"=>32, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GTPase_activity_of_recombinant_w_Bm_FtsZ_/378889", "title"=>"GTPase activity of recombinant wBm-FtsZ.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 11:18:41"}
{"files"=>["https://ndownloader.figshare.com/files/708460"], "description"=>"FtsZ protein from Wolbachia (A) and E. coli (B) were expressed in E. coli with a His-tag at the N-terminus and purified by nickel-affinity chromatography. The apparent molecular weight (indicated) from SDS–PAGE was consistent with the predicted molecular size. Protein marker (M), total protein lysate (T), insoluble proteins (In), soluble (S) and purified FtsZ proteins (P) are shown.", "links"=>[], "tags"=>["purification", "recombinant", "ftsz"], "article_id"=>378819, "categories"=>["Biotechnology", "Biochemistry", "Infectious Diseases", "Pharmacology"], "users"=>["Zhiru Li", "Amanda L. Garner", "Christian Gloeckner", "Kim D. Janda", "Clotilde K. Carlow"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001411.g002", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_and_purification_of_recombinant_FtsZ_proteins_/378819", "title"=>"Expression and purification of recombinant FtsZ proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 11:18:17"}
{"files"=>["https://ndownloader.figshare.com/files/709162"], "description"=>"*Only major E. coli cell-division proteins are shown.", "links"=>[], "tags"=>["machinery"], "article_id"=>379522, "categories"=>["Biotechnology", "Biochemistry", "Infectious Diseases", "Pharmacology"], "users"=>["Zhiru Li", "Amanda L. Garner", "Christian Gloeckner", "Kim D. Janda", "Clotilde K. Carlow"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001411.t001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_cell_division_machinery_present_in_Wolbachia_and_E_coli_/379522", "title"=>"Comparison of cell division machinery present in Wolbachia and E. coli*.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 11:22:03"}
{"files"=>["https://ndownloader.figshare.com/files/708996"], "description"=>"General scaffolds for small molecule library compounds (A). Structure of berberine (B). FtsZ inhibitors identified from the initial high-throughput screen (C). FtsZ inhibitors identified from SAR studies (D).", "links"=>[], "tags"=>["ftsz", "inhibitors"], "article_id"=>379363, "categories"=>["Biotechnology", "Biochemistry", "Infectious Diseases", "Pharmacology"], "users"=>["Zhiru Li", "Amanda L. Garner", "Christian Gloeckner", "Kim D. Janda", "Clotilde K. Carlow"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001411.g007", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structures_of_FtsZ_inhibitors_and_scaffolds_/379363", "title"=>"Structures of FtsZ inhibitors and scaffolds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 11:21:10"}
{"files"=>["https://ndownloader.figshare.com/files/708373"], "description"=>"Female adult worm, male adult worm, microfilaria, L3 and L4 were analyzed. The ratio of ftsZ to 16S rRNA (A) represents ftsZ gene expression, while the ratio of Wolbachia 16S to B. malayi 18S rRNA (B) represents the relative abundance of Wolbachia in B. malayi. The data obtained from triplicate samples are expressed as a mean ± standard deviation.", "links"=>[], "tags"=>["stages"], "article_id"=>378731, "categories"=>["Biotechnology", "Biochemistry", "Infectious Diseases", "Pharmacology"], "users"=>["Zhiru Li", "Amanda L. Garner", "Christian Gloeckner", "Kim D. Janda", "Clotilde K. Carlow"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001411.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Wolbachia_ftsZ_gene_expression_in_various_developmental_stages_of_B_malayi_/378731", "title"=>"Wolbachia ftsZ gene expression in various developmental stages of B. malayi.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 11:17:46"}
{"files"=>["https://ndownloader.figshare.com/files/709070"], "description"=>"wBm-FtsZ (▪ and •) and Ec-FtsZ (□ and ○) were compared. Panel A, compounds were tested at the concentration of 30, 40, 50, 60, 70, 80, 90, and 100 µM and the experiment were performed in duplicate, the mean value was plotted. Panel B, compounds were tested at the concentration of 10, 20, 40, 60, 80, and 100 µM and the experiments were performed in triplicate, the mean ± standard deviation was plotted.", "links"=>[], "tags"=>["gtpase"], "article_id"=>379434, "categories"=>["Biotechnology", "Biochemistry", "Infectious Diseases", "Pharmacology"], "users"=>["Zhiru Li", "Amanda L. Garner", "Christian Gloeckner", "Kim D. Janda", "Clotilde K. Carlow"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001411.g008", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_GTPase_activity_by_small_molecules_/379434", "title"=>"Inhibition of GTPase activity by small molecules.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 11:21:33"}
{"files"=>["https://ndownloader.figshare.com/files/708796"], "description"=>"Panel A, overnight growth of E. coli was determined in the presence of various concentrations of berberine sulfate. Percentage of growth is indicated as 100×(OD600 nm with berberine/OD600 nm without berberine). The data obtained from triplicate samples are expressed as a mean ± standard deviation. Panel B, log-phase (5 h) growth (OD600 nm) of E. coli was determined in the presence of various concentrations (10–70 µM) of berberine sulphate. Panel C, DIC micrographs of E. coli untreated (0 µM) or treated with 40 µM or 80 µM berberine sulfate. Panel D, effect of berberine sulfate on E. coli viability. Viability of berberine sulfate-treated (24 hours) cells was evaluated by plating serial dilutions (10−2–10−7) of bacteria (Output shown in duplicate) on a petri dish and incubation overnight at 30 °C. The number of bacteria present in the inoculum used in the experiment (Input) is also shown.", "links"=>[], "tags"=>["sulfate", "inhibition"], "article_id"=>379159, "categories"=>["Biotechnology", "Biochemistry", "Infectious Diseases", "Pharmacology"], "users"=>["Zhiru Li", "Amanda L. Garner", "Christian Gloeckner", "Kim D. Janda", "Clotilde K. Carlow"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001411.g006", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Berberine_sulfate_inhibition_of_E_coli_growth_/379159", "title"=>"Berberine sulfate inhibition of E. coli growth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 11:20:07"}
{"files"=>["https://ndownloader.figshare.com/files/708663"], "description"=>"Motility of adult female (A) and male (D) worms, and microfilariae (C) was examined following 6 days exposure to varying amounts (5–40 µM) of berberine sulfate. 10 µM doxycycline was included as a control. Motility was scored as described <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001411#pntd.0001411-Rao2\" target=\"_blank\">[38]</a> and expressed as % of motility relative to motility scored on day 0 of the experiment. Micofilariae production (B) was determined at each time point by counting the number of microfilaria present in 1 mL spent culture media. The data obtained from triplicate samples are expressed as a mean ± standard deviation.", "links"=>[], "tags"=>["berberine", "sulfate", "parasites"], "article_id"=>379027, "categories"=>["Biotechnology", "Biochemistry", "Infectious Diseases", "Pharmacology"], "users"=>["Zhiru Li", "Amanda L. Garner", "Christian Gloeckner", "Kim D. Janda", "Clotilde K. Carlow"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001411.g005", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_berberine_sulfate_on_B_malayi_parasites_in_culture_/379027", "title"=>"Effect of berberine sulfate on B. malayi parasites in culture.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 11:19:26"}

PMC Usage Stats 173917 Feb 14:30 UTC

PMC Usage Stats | Further Information

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Relative Metric 57353205 Apr 16:21 UTC

Relative Metric

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F1000Prime24 Feb 11:57 UTC

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