Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy.
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 mal...
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ftdoajarticles:oai:doaj.org/article:4e07698d7d1e498eb960351f72c182d7 2023-05-15T15:07:48+02:00 Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy. Zhiru Li Amanda L Garner Christian Gloeckner Kim D Janda Clotilde K Carlow 2011-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001411 https://doaj.org/article/4e07698d7d1e498eb960351f72c182d7 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3226453?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001411 https://doaj.org/article/4e07698d7d1e498eb960351f72c182d7 PLoS Neglected Tropical Diseases, Vol 5, Iss 11, p e1411 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001411 2022-12-31T00:12:44Z 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 GenBankā¢ Data Bank under the accession number wAlB-FtsZ (JN616286). Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 11 e1411 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Zhiru Li Amanda L Garner Christian Gloeckner Kim D Janda Clotilde K Carlow Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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 GenBankā¢ Data Bank under the accession number wAlB-FtsZ (JN616286). |
format |
Article in Journal/Newspaper |
author |
Zhiru Li Amanda L Garner Christian Gloeckner Kim D Janda Clotilde K Carlow |
author_facet |
Zhiru Li Amanda L Garner Christian Gloeckner Kim D Janda Clotilde K Carlow |
author_sort |
Zhiru Li |
title |
Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy. |
title_short |
Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy. |
title_full |
Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy. |
title_fullStr |
Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy. |
title_full_unstemmed |
Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy. |
title_sort |
targeting the wolbachia cell division protein ftsz as a new approach for antifilarial therapy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001411 https://doaj.org/article/4e07698d7d1e498eb960351f72c182d7 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 11, p e1411 (2011) |
op_relation |
http://europepmc.org/articles/PMC3226453?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001411 https://doaj.org/article/4e07698d7d1e498eb960351f72c182d7 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001411 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
5 |
container_issue |
11 |
container_start_page |
e1411 |
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1766339227044282368 |