Two Small Molecules Block Oral Epithelial Cell Invasion by Porphyromons gingivalis
Porphyromonas gingivalis is a keystone pathogen of periodontitis. One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptation and survival in the gingival environment...
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| description | Porphyromonas gingivalis is a keystone pathogen of periodontitis. One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptation and survival in the gingival environment. In this study, we investigated two small compounds, Alop1 and dynasore, for their role in inhibition of P. gingivalis invasion. Using confocal microscopy, we showed that these two compounds significantly reduced invasion of P. gingivalis and its outer membrane vesicles into human oral keratinocytes in a dose-dependent manner. The inhibitory effects of dynasore, a dynamin inhibitor, on the bacterial entry is consistent with the notion that P. gingivalis invasion is mediated by a clathrin-mediated endocytic machinery. We also observed that microtubule arrangement, but not actin, was altered in the host cells treated with Alop1 or dynasore, suggesting an involvement of microtubule in this inhibitory activity. This work provides an opportunity to develop compounds against P. gingivalis infection. |
| doi_str_mv | 10.1371/journal.pone.0149618 |
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One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptation and survival in the gingival environment. In this study, we investigated two small compounds, Alop1 and dynasore, for their role in inhibition of P. gingivalis invasion. Using confocal microscopy, we showed that these two compounds significantly reduced invasion of P. gingivalis and its outer membrane vesicles into human oral keratinocytes in a dose-dependent manner. The inhibitory effects of dynasore, a dynamin inhibitor, on the bacterial entry is consistent with the notion that P. gingivalis invasion is mediated by a clathrin-mediated endocytic machinery. We also observed that microtubule arrangement, but not actin, was altered in the host cells treated with Alop1 or dynasore, suggesting an involvement of microtubule in this inhibitory activity. This work provides an opportunity to develop compounds against P. gingivalis infection.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0149618</identifier><identifier>PMID: 26894834</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Actin ; Bacteria ; Bacterial infections ; Biology and Life Sciences ; Causes of ; Cells, Cultured ; Chinese medicine ; Clathrin ; Confocal microscopy ; Dentistry ; Development and progression ; Dynamin ; Dynamins - antagonists & inhibitors ; Endocytosis - drug effects ; Epithelial cells ; Fibroblasts ; Genetic aspects ; Gram-negative bacteria ; Humans ; Hydrazones - pharmacology ; Infections ; Influenza ; Keratinocytes ; Keratinocytes - drug effects ; Keratinocytes - microbiology ; Ligands ; Lipids ; Machinery ; Machinery and equipment ; Medicine and Health Sciences ; Membrane vesicles ; Microscopy ; Microtubules - microbiology ; Mouth Mucosa - microbiology ; Pathogens ; Periodontitis ; Physiological aspects ; Piperidines - pharmacology ; Porphyromonas gingivalis ; Porphyromonas gingivalis - drug effects ; Porphyromonas gingivalis - physiology ; Proteins ; Research and Analysis Methods ; Virulence (Microbiology)</subject><ispartof>PloS one, 2016-02, Vol.11 (2), p.e0149618-e0149618</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Ho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Ho et al 2016 Ho et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-83943cb6ff43cbaf67166895bdbc19844295279019ad3c5fa95b365967a51fb53</citedby><cites>FETCH-LOGICAL-c692t-83943cb6ff43cbaf67166895bdbc19844295279019ad3c5fa95b365967a51fb53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760928/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760928/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26894834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kreth, Jens</contributor><creatorcontrib>Ho, Meng-Hsuan</creatorcontrib><creatorcontrib>Huang, Li</creatorcontrib><creatorcontrib>Goodwin, J Shawn</creatorcontrib><creatorcontrib>Dong, Xinhong</creatorcontrib><creatorcontrib>Chen, Chin-Ho</creatorcontrib><creatorcontrib>Xie, Hua</creatorcontrib><title>Two Small Molecules Block Oral Epithelial Cell Invasion by Porphyromons gingivalis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Porphyromonas gingivalis is a keystone pathogen of periodontitis. One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptation and survival in the gingival environment. In this study, we investigated two small compounds, Alop1 and dynasore, for their role in inhibition of P. gingivalis invasion. Using confocal microscopy, we showed that these two compounds significantly reduced invasion of P. gingivalis and its outer membrane vesicles into human oral keratinocytes in a dose-dependent manner. The inhibitory effects of dynasore, a dynamin inhibitor, on the bacterial entry is consistent with the notion that P. gingivalis invasion is mediated by a clathrin-mediated endocytic machinery. We also observed that microtubule arrangement, but not actin, was altered in the host cells treated with Alop1 or dynasore, suggesting an involvement of microtubule in this inhibitory activity. This work provides an opportunity to develop compounds against P. gingivalis infection.</description><subject>Actin</subject><subject>Bacteria</subject><subject>Bacterial infections</subject><subject>Biology and Life Sciences</subject><subject>Causes of</subject><subject>Cells, Cultured</subject><subject>Chinese medicine</subject><subject>Clathrin</subject><subject>Confocal microscopy</subject><subject>Dentistry</subject><subject>Development and progression</subject><subject>Dynamin</subject><subject>Dynamins - antagonists & inhibitors</subject><subject>Endocytosis - drug effects</subject><subject>Epithelial cells</subject><subject>Fibroblasts</subject><subject>Genetic aspects</subject><subject>Gram-negative bacteria</subject><subject>Humans</subject><subject>Hydrazones - pharmacology</subject><subject>Infections</subject><subject>Influenza</subject><subject>Keratinocytes</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - microbiology</subject><subject>Ligands</subject><subject>Lipids</subject><subject>Machinery</subject><subject>Machinery and equipment</subject><subject>Medicine and Health Sciences</subject><subject>Membrane vesicles</subject><subject>Microscopy</subject><subject>Microtubules - microbiology</subject><subject>Mouth Mucosa - microbiology</subject><subject>Pathogens</subject><subject>Periodontitis</subject><subject>Physiological aspects</subject><subject>Piperidines - pharmacology</subject><subject>Porphyromonas gingivalis</subject><subject>Porphyromonas gingivalis - drug effects</subject><subject>Porphyromonas gingivalis - physiology</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Virulence (Microbiology)</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNklGP1CAUhRujcdfVf2C0iYnRhxmhUCgvJutk1UnWjNldfSWUQoeRlgrt6Px7Gae7mZp9MDxA4LvnwuEkyXMI5hBR-G7jBt8KO-9cq-YAYkZg8SA5hQxlM5IB9PBofZI8CWEDQI4KQh4nJxkpGC4QPk2ubn659LoR1qZfnFVysCqkH6yTP9KVFza96Ey_VtbE5UJFaNluRTCuTctd-tX5br3zrnFtSGvT1mYrrAlPk0da2KCejfNZ8u3jxc3i8-xy9Wm5OL-cScKyflYghpEsidb7SWhCIYnXysuqlJAVGGcszygDkIkKyVyLeIRIzggVOdRljs6SlwfdzrrARzsCh5TCjGYQZJFYHojKiQ3vvGmE33EnDP-74XzNhe-NtIprxIpcMEVzRLGqsEAYlhXBGlcaVUJHrfdjt6FsVCVV20d_JqLTk9asee22HFMCWFZEgTejgHc_BxV63pggo6eiVW7Y35tQklFASURf_YPe_7qRqkV8gGm1i33lXpSfY4woYJTASM3voeKoVGNkzI42cX9S8HZSEJle_e5rMYTAl9dX_8-uvk_Z10fsWgnbr4OzQx_TFKYgPoDSuxC80ncmQ8D30b91g--jz8fox7IXxx90V3SbdfQH3vD9kA</recordid><startdate>20160219</startdate><enddate>20160219</enddate><creator>Ho, Meng-Hsuan</creator><creator>Huang, Li</creator><creator>Goodwin, J Shawn</creator><creator>Dong, Xinhong</creator><creator>Chen, Chin-Ho</creator><creator>Xie, Hua</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160219</creationdate><title>Two Small Molecules Block Oral Epithelial Cell Invasion by Porphyromons gingivalis</title><author>Ho, Meng-Hsuan ; Huang, Li ; Goodwin, J Shawn ; Dong, Xinhong ; Chen, Chin-Ho ; Xie, Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-83943cb6ff43cbaf67166895bdbc19844295279019ad3c5fa95b365967a51fb53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Actin</topic><topic>Bacteria</topic><topic>Bacterial infections</topic><topic>Biology and Life Sciences</topic><topic>Causes of</topic><topic>Cells, Cultured</topic><topic>Chinese medicine</topic><topic>Clathrin</topic><topic>Confocal microscopy</topic><topic>Dentistry</topic><topic>Development and progression</topic><topic>Dynamin</topic><topic>Dynamins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ho, Meng-Hsuan</au><au>Huang, Li</au><au>Goodwin, J Shawn</au><au>Dong, Xinhong</au><au>Chen, Chin-Ho</au><au>Xie, Hua</au><au>Kreth, Jens</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Two Small Molecules Block Oral Epithelial Cell Invasion by Porphyromons gingivalis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-02-19</date><risdate>2016</risdate><volume>11</volume><issue>2</issue><spage>e0149618</spage><epage>e0149618</epage><pages>e0149618-e0149618</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Porphyromonas gingivalis is a keystone pathogen of periodontitis. One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptation and survival in the gingival environment. In this study, we investigated two small compounds, Alop1 and dynasore, for their role in inhibition of P. gingivalis invasion. Using confocal microscopy, we showed that these two compounds significantly reduced invasion of P. gingivalis and its outer membrane vesicles into human oral keratinocytes in a dose-dependent manner. The inhibitory effects of dynasore, a dynamin inhibitor, on the bacterial entry is consistent with the notion that P. gingivalis invasion is mediated by a clathrin-mediated endocytic machinery. We also observed that microtubule arrangement, but not actin, was altered in the host cells treated with Alop1 or dynasore, suggesting an involvement of microtubule in this inhibitory activity. This work provides an opportunity to develop compounds against P. gingivalis infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26894834</pmid><doi>10.1371/journal.pone.0149618</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Actin Bacteria Bacterial infections Biology and Life Sciences Causes of Cells, Cultured Chinese medicine Clathrin Confocal microscopy Dentistry Development and progression Dynamin Dynamins - antagonists & inhibitors Endocytosis - drug effects Epithelial cells Fibroblasts Genetic aspects Gram-negative bacteria Humans Hydrazones - pharmacology Infections Influenza Keratinocytes Keratinocytes - drug effects Keratinocytes - microbiology Ligands Lipids Machinery Machinery and equipment Medicine and Health Sciences Membrane vesicles Microscopy Microtubules - microbiology Mouth Mucosa - microbiology Pathogens Periodontitis Physiological aspects Piperidines - pharmacology Porphyromonas gingivalis Porphyromonas gingivalis - drug effects Porphyromonas gingivalis - physiology Proteins Research and Analysis Methods Virulence (Microbiology) |
| title | Two Small Molecules Block Oral Epithelial Cell Invasion by Porphyromons gingivalis |
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