The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa
Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to...
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| description | Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by 5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans. |
| doi_str_mv | 10.1371/journal.pone.0169180 |
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S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by <3-logs. A combination of 0.05 mg PlySs2 + 0.05 mg gentamicin reduced S. suis by >5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0169180</identifier><identifier>PMID: 28046082</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; Bacteria ; Bacteriophages ; Biology and Life Sciences ; Cloning ; Cloning, Molecular ; Drugs ; Enzymes ; Enzymes - pharmacology ; Epidemiology ; Female ; Genetic aspects ; Genomes ; Gentamicin ; Gentamicins - administration & dosage ; Gram-positive bacteria ; Health aspects ; Hogs ; Immunology ; Laboratories ; Lysins ; Medical research ; Medicine and Health Sciences ; Meningitis ; Mice ; Minimum inhibitory concentration ; Mucosa ; Nasal Mucosa - microbiology ; Pathogenesis ; Penicillin ; Penicillins - therapeutic use ; Phages ; Preventive medicine ; Serotypes ; Staphylococcus aureus ; Staphylococcus infections ; Streptococcal Infections - drug therapy ; Streptococcus ; Streptococcus infections ; Streptococcus Phages ; Streptococcus suis ; Streptococcus suis - pathogenicity ; Sus scrofa ; Swine ; Swine Diseases - drug therapy ; Virulence (Microbiology) ; Zoonoses ; Zoonoses - drug therapy ; Zoonoses - microbiology</subject><ispartof>PloS one, 2017-01, Vol.12 (1), p.e0169180-e0169180</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Gilmer 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>2017 Gilmer et al 2017 Gilmer et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6400-618ef753e861549fec23c829270f6cca39aa1e25c4f32fc5dc1cdf78dabd57333</citedby><cites>FETCH-LOGICAL-c6400-618ef753e861549fec23c829270f6cca39aa1e25c4f32fc5dc1cdf78dabd57333</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/PMC5207509/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207509/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28046082$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Melo-Cristino, Jose</contributor><creatorcontrib>Gilmer, Daniel B</creatorcontrib><creatorcontrib>Schmitz, Jonathan E</creatorcontrib><creatorcontrib>Thandar, Mya</creatorcontrib><creatorcontrib>Euler, Chad W</creatorcontrib><creatorcontrib>Fischetti, Vincent A</creatorcontrib><title>The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by <3-logs. A combination of 0.05 mg PlySs2 + 0.05 mg gentamicin reduced S. suis by >5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Bacteriophages</subject><subject>Biology and Life Sciences</subject><subject>Cloning</subject><subject>Cloning, Molecular</subject><subject>Drugs</subject><subject>Enzymes</subject><subject>Enzymes - pharmacology</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Gentamicin</subject><subject>Gentamicins - administration & dosage</subject><subject>Gram-positive bacteria</subject><subject>Health aspects</subject><subject>Hogs</subject><subject>Immunology</subject><subject>Laboratories</subject><subject>Lysins</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Meningitis</subject><subject>Mice</subject><subject>Minimum inhibitory concentration</subject><subject>Mucosa</subject><subject>Nasal Mucosa - microbiology</subject><subject>Pathogenesis</subject><subject>Penicillin</subject><subject>Penicillins - therapeutic use</subject><subject>Phages</subject><subject>Preventive medicine</subject><subject>Serotypes</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus infections</subject><subject>Streptococcal Infections - drug therapy</subject><subject>Streptococcus</subject><subject>Streptococcus infections</subject><subject>Streptococcus Phages</subject><subject>Streptococcus suis</subject><subject>Streptococcus suis - pathogenicity</subject><subject>Sus scrofa</subject><subject>Swine</subject><subject>Swine Diseases - drug therapy</subject><subject>Virulence (Microbiology)</subject><subject>Zoonoses</subject><subject>Zoonoses - drug therapy</subject><subject>Zoonoses - microbiology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</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>eNqNk0tvEzEQx1cIREvhGyBYCQnBIcHv9V6QqvKKFNSKFK6W4x0nrpx1au8iwqfHabZVgnqofLA1_s3f8_AUxUuMxphW-MNV6GOr_XgdWhgjLGos0aPiGNeUjARB9PHe-ah4ltIVQpxKIZ4WR0QiJpAkx8XscgnlxVIvoJxukmvLC7-ZJVJ-AhN8aN1fSOWsi7DuggnG9KlMvUuljWFVfu-ja6GctF3UrU7aZ4sJST8vnljtE7wY9pPi55fPl2ffRtPzr5Oz0-nICIbQSGAJtuIUpMCc1RYMoUaSmlTICmM0rbXGQLhhlhJreGOwaWwlGz1veEUpPSle73TXPiQ11CMpLDlHghEqMjHZEU3QV2od3UrHjQraqRtDiAulY-eMB8Ula-ZM1obThjEhpKmhqpgFJkES0Fnr4_BaP19BY2Cbtj8QPbxp3VItwm_FCao4qrPAu0EghuseUqdWLhnwXrcQ-pu46xwAw-whKKdESiQz-uY_9P5CDNRC51xda0MO0WxF1SmrBKEVI1tqfA-VVwMrZ_I_sy7bDxzeHzhkpoM_3UL3KanJ7MfD2fNfh-zbPXYJ2nfLFHzfudCmQ5DtQBNDShHsXT8wUtsxua2G2o6JGsYku73a7-Wd0-1c0H_EuAve</recordid><startdate>20170103</startdate><enddate>20170103</enddate><creator>Gilmer, Daniel B</creator><creator>Schmitz, Jonathan E</creator><creator>Thandar, Mya</creator><creator>Euler, Chad W</creator><creator>Fischetti, Vincent A</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>20170103</creationdate><title>The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa</title><author>Gilmer, Daniel B ; Schmitz, Jonathan E ; Thandar, Mya ; Euler, Chad W ; Fischetti, Vincent A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6400-618ef753e861549fec23c829270f6cca39aa1e25c4f32fc5dc1cdf78dabd57333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibiotics</topic><topic>Bacteria</topic><topic>Bacteriophages</topic><topic>Biology and Life Sciences</topic><topic>Cloning</topic><topic>Cloning, Molecular</topic><topic>Drugs</topic><topic>Enzymes</topic><topic>Enzymes - pharmacology</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Gentamicin</topic><topic>Gentamicins - administration & dosage</topic><topic>Gram-positive bacteria</topic><topic>Health aspects</topic><topic>Hogs</topic><topic>Immunology</topic><topic>Laboratories</topic><topic>Lysins</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Meningitis</topic><topic>Mice</topic><topic>Minimum inhibitory concentration</topic><topic>Mucosa</topic><topic>Nasal Mucosa - microbiology</topic><topic>Pathogenesis</topic><topic>Penicillin</topic><topic>Penicillins - therapeutic use</topic><topic>Phages</topic><topic>Preventive medicine</topic><topic>Serotypes</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus infections</topic><topic>Streptococcal Infections - 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S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by <3-logs. A combination of 0.05 mg PlySs2 + 0.05 mg gentamicin reduced S. suis by >5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28046082</pmid><doi>10.1371/journal.pone.0169180</doi><tpages>e0169180</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Anti-Bacterial Agents - pharmacology Antibiotics Bacteria Bacteriophages Biology and Life Sciences Cloning Cloning, Molecular Drugs Enzymes Enzymes - pharmacology Epidemiology Female Genetic aspects Genomes Gentamicin Gentamicins - administration & dosage Gram-positive bacteria Health aspects Hogs Immunology Laboratories Lysins Medical research Medicine and Health Sciences Meningitis Mice Minimum inhibitory concentration Mucosa Nasal Mucosa - microbiology Pathogenesis Penicillin Penicillins - therapeutic use Phages Preventive medicine Serotypes Staphylococcus aureus Staphylococcus infections Streptococcal Infections - drug therapy Streptococcus Streptococcus infections Streptococcus Phages Streptococcus suis Streptococcus suis - pathogenicity Sus scrofa Swine Swine Diseases - drug therapy Virulence (Microbiology) Zoonoses Zoonoses - drug therapy Zoonoses - microbiology |
| title | The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T09%3A37%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Phage%20Lysin%20PlySs2%20Decolonizes%20Streptococcus%20suis%20from%20Murine%20Intranasal%20Mucosa&rft.jtitle=PloS%20one&rft.au=Gilmer,%20Daniel%20B&rft.date=2017-01-03&rft.volume=12&rft.issue=1&rft.spage=e0169180&rft.epage=e0169180&rft.pages=e0169180-e0169180&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0169180&rft_dat=%3Cgale_plos_%3EA476237426%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1855064236&rft_id=info:pmid/28046082&rft_galeid=A476237426&rft_doaj_id=oai_doaj_org_article_584db489c53d44668c9e774fe48e82ea&rfr_iscdi=true |