Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention
Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacteria...
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description | Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections. |
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Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0016963</identifier><identifier>PMID: 21347240</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alveoli ; Amino Acid Sequence ; Analysis ; Animals ; Antibiotics ; Antigens ; Bacteria ; Bacterial diseases ; Bacterial infections ; Bacteriophages - pathogenicity ; Bacteriophages - physiology ; Biocompatibility ; Biofilms ; Biology ; Bronchus ; Burkholderia cenocepacia ; Catheters ; Computational fluid dynamics ; Correlation analysis ; Cystic fibrosis ; Cystic Fibrosis - microbiology ; Cystic Fibrosis - prevention & control ; Cystic Fibrosis - therapy ; Cytokines ; Cytotoxicity ; Drug Resistance, Multiple, Bacterial ; Environmental monitoring ; Enzymes ; Epidemiology ; Health aspects ; Histology ; Host range ; Humans ; Immunohistochemistry ; Infection ; Infections ; Inflammation ; Lung - microbiology ; Lungs ; Male ; Medicine ; Mice ; Microscopy ; Molecular biology ; Molecular Sequence Data ; Multidrug resistance ; Optimization ; Phages ; Pneumonia ; Prevention ; Preventive medicine ; Pseudomonas aeruginosa ; Pseudomonas aeruginosa - pathogenicity ; Pseudomonas aeruginosa - virology ; Species Specificity ; Strains (organisms) ; Survival ; Therapeutic applications ; Therapy ; Toxicity ; Viral Proteins - chemistry ; Viral Proteins - metabolism ; Viruses</subject><ispartof>PloS one, 2011-02, Vol.6 (2), p.e16963-e16963</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>Copyright Public Library of Science Feb 2011</rights><rights>Morello et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-12ea6138ff8c243008437badf59c9059cd504476a7e56ce95dab7f305abc9f8a3</citedby><cites>FETCH-LOGICAL-c757t-12ea6138ff8c243008437badf59c9059cd504476a7e56ce95dab7f305abc9f8a3</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/PMC3039662/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039662/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21347240$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morello, Eric</creatorcontrib><creatorcontrib>Saussereau, Emilie</creatorcontrib><creatorcontrib>Maura, Damien</creatorcontrib><creatorcontrib>Huerre, Michel</creatorcontrib><creatorcontrib>Touqui, Lhousseine</creatorcontrib><creatorcontrib>Debarbieux, Laurent</creatorcontrib><title>Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. 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microbiology</subject><subject>Lungs</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Microscopy</subject><subject>Molecular biology</subject><subject>Molecular Sequence Data</subject><subject>Multidrug resistance</subject><subject>Optimization</subject><subject>Phages</subject><subject>Pneumonia</subject><subject>Prevention</subject><subject>Preventive medicine</subject><subject>Pseudomonas aeruginosa</subject><subject>Pseudomonas aeruginosa - pathogenicity</subject><subject>Pseudomonas aeruginosa - virology</subject><subject>Species Specificity</subject><subject>Strains (organisms)</subject><subject>Survival</subject><subject>Therapeutic applications</subject><subject>Therapy</subject><subject>Toxicity</subject><subject>Viral Proteins - chemistry</subject><subject>Viral Proteins - metabolism</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0tv1DAQxyMEoqXwDRBEQgJx2MWO8zIHpKrisVKlVryu1sQZZ10lcbCdwp746jhsWm1QDyhSbE9-M-P5ZyaKnlKypqygb67MaHto14PpcU0IzXnO7kXHlLNklSeE3T_YH0WPnLsiJGNlnj-MjhLK0iJJyXH0-3JsO9OD3cUVSI9Wm2ELDcZ-ixaGXWz6-NLhWJuJcjGgHRvdGwex3DmvZax0ZY3TLnbegu7d22CxzocjDi725ifYOqwWwXfY-xj6Oh4sXoe9Nv3j6IGC1uGTeT2Jvn14__Xs0-r84uPm7PR8JYus8CuaIOSUlUqVMkkZIWXKigpqlXHJSXjVGUnTIocCs1wiz2qoCsVIBpXkqgR2Ej3fxx1a48SsnRM04QnlSUppIDZ7ojZwJQaruyCKMKDFX4OxjQAbCm5RUKJSyMoMiazTLC1B1VM2XgCTAIUMsd7N2caqw1qGWi20i6DLL73eisZcC0YYz_MkBHg1B7Dmx4jOi047iW0LPZrRiTJjnIcumK794h_y7uJmqoFwf90rE9LKKaY4DbLxIF7OA7W-gwpPjZ2Woc-UDvaFw-uFQ2A8_vINjM6JzZfP_89efF-yLw_YLULrt86049Qxbgmme1CGHnQW1a3GlIhpTG7UENOYiHlMgtuzw_9z63QzF-wPB5ERFg</recordid><startdate>20110215</startdate><enddate>20110215</enddate><creator>Morello, Eric</creator><creator>Saussereau, Emilie</creator><creator>Maura, Damien</creator><creator>Huerre, Michel</creator><creator>Touqui, Lhousseine</creator><creator>Debarbieux, Laurent</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>AEUYN</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>20110215</creationdate><title>Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention</title><author>Morello, Eric ; Saussereau, Emilie ; Maura, Damien ; Huerre, Michel ; Touqui, Lhousseine ; Debarbieux, Laurent</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-12ea6138ff8c243008437badf59c9059cd504476a7e56ce95dab7f305abc9f8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Alveoli</topic><topic>Amino Acid Sequence</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antibiotics</topic><topic>Antigens</topic><topic>Bacteria</topic><topic>Bacterial diseases</topic><topic>Bacterial infections</topic><topic>Bacteriophages - pathogenicity</topic><topic>Bacteriophages - physiology</topic><topic>Biocompatibility</topic><topic>Biofilms</topic><topic>Biology</topic><topic>Bronchus</topic><topic>Burkholderia cenocepacia</topic><topic>Catheters</topic><topic>Computational fluid dynamics</topic><topic>Correlation analysis</topic><topic>Cystic fibrosis</topic><topic>Cystic Fibrosis - microbiology</topic><topic>Cystic Fibrosis - prevention & control</topic><topic>Cystic Fibrosis - therapy</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Drug Resistance, Multiple, Bacterial</topic><topic>Environmental monitoring</topic><topic>Enzymes</topic><topic>Epidemiology</topic><topic>Health aspects</topic><topic>Histology</topic><topic>Host range</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Infection</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Lung - microbiology</topic><topic>Lungs</topic><topic>Male</topic><topic>Medicine</topic><topic>Mice</topic><topic>Microscopy</topic><topic>Molecular biology</topic><topic>Molecular Sequence Data</topic><topic>Multidrug resistance</topic><topic>Optimization</topic><topic>Phages</topic><topic>Pneumonia</topic><topic>Prevention</topic><topic>Preventive medicine</topic><topic>Pseudomonas aeruginosa</topic><topic>Pseudomonas aeruginosa - 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Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21347240</pmid><doi>10.1371/journal.pone.0016963</doi><tpages>e16963</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Alveoli Amino Acid Sequence Analysis Animals Antibiotics Antigens Bacteria Bacterial diseases Bacterial infections Bacteriophages - pathogenicity Bacteriophages - physiology Biocompatibility Biofilms Biology Bronchus Burkholderia cenocepacia Catheters Computational fluid dynamics Correlation analysis Cystic fibrosis Cystic Fibrosis - microbiology Cystic Fibrosis - prevention & control Cystic Fibrosis - therapy Cytokines Cytotoxicity Drug Resistance, Multiple, Bacterial Environmental monitoring Enzymes Epidemiology Health aspects Histology Host range Humans Immunohistochemistry Infection Infections Inflammation Lung - microbiology Lungs Male Medicine Mice Microscopy Molecular biology Molecular Sequence Data Multidrug resistance Optimization Phages Pneumonia Prevention Preventive medicine Pseudomonas aeruginosa Pseudomonas aeruginosa - pathogenicity Pseudomonas aeruginosa - virology Species Specificity Strains (organisms) Survival Therapeutic applications Therapy Toxicity Viral Proteins - chemistry Viral Proteins - metabolism Viruses |
title | Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention |
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