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Exploring the feasibility of bacteriocins EntK1 and EntEJ97s in treatment of systemic vancomycin resistant enterococci infections in mice
Enterocins K1 and EJ97 have specific antimicrobial activity against Enterococcus faecium and Enterococcus faecalis, respectively. The aim of this study was to investigate the utility of these enterocins for in vivo treatment of systemic enterococcal infections. The antimicrobial effect in blood was...
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Published in: | Journal of applied microbiology 2024-03, Vol.135 (3) |
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container_title | Journal of applied microbiology |
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creator | Reinseth, Ingvild Diep, Dzung B Kjos, Morten Tønnesen, Hanne H Carlsen, Harald |
description | Enterocins K1 and EJ97 have specific antimicrobial activity against Enterococcus faecium and Enterococcus faecalis, respectively. The aim of this study was to investigate the utility of these enterocins for in vivo treatment of systemic enterococcal infections.
The antimicrobial effect in blood was analysed and compared against the effect in saline. Colony forming unit counts revealed that the enterocins killed all the bacteria within 1 hour. Additionally, the bactericidal effect against E. faecalis was more rapid in blood, indicating a possible synergy between EntEJ97 and blood. Importantly, no enterocin resistant mutants emerged in these experiments. Injecting the enterocins intraperitoneally in an in vivo mouse model and using fluorescence and minimum inhibitory concentration determination to estimate concentrations of the peptides in plasma, indicate that the enterocins exist in circulation in therapeutic concentrations. Alanine aminotransferase detection, and haemolysis analysis indicates that there is no detectable liver damage or haemolytic effect after injection.
The study revealed that EntK1 and EntEJ97 are able to kill all bacteria ex vivo in the presence of blood. In vivo experiments determine that the enterocins exist in circulation in therapeutic concentrations without causing liver damage or haemolysis. Future experiments should test these peptides for treatment of infection in a relevant in vivo model. |
doi_str_mv | 10.1093/jambio/lxae054 |
format | article |
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The antimicrobial effect in blood was analysed and compared against the effect in saline. Colony forming unit counts revealed that the enterocins killed all the bacteria within 1 hour. Additionally, the bactericidal effect against E. faecalis was more rapid in blood, indicating a possible synergy between EntEJ97 and blood. Importantly, no enterocin resistant mutants emerged in these experiments. Injecting the enterocins intraperitoneally in an in vivo mouse model and using fluorescence and minimum inhibitory concentration determination to estimate concentrations of the peptides in plasma, indicate that the enterocins exist in circulation in therapeutic concentrations. Alanine aminotransferase detection, and haemolysis analysis indicates that there is no detectable liver damage or haemolytic effect after injection.
The study revealed that EntK1 and EntEJ97 are able to kill all bacteria ex vivo in the presence of blood. In vivo experiments determine that the enterocins exist in circulation in therapeutic concentrations without causing liver damage or haemolysis. Future experiments should test these peptides for treatment of infection in a relevant in vivo model.</description><identifier>ISSN: 1365-2672</identifier><identifier>EISSN: 1365-2672</identifier><identifier>DOI: 10.1093/jambio/lxae054</identifier><identifier>PMID: 38439668</identifier><language>eng</language><publisher>England</publisher><ispartof>Journal of applied microbiology, 2024-03, Vol.135 (3)</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c225t-45f78b8fb67df46f666dd7dc9d447c9e4389a955eb1a71ab8173b5632a5c569d3</citedby><cites>FETCH-LOGICAL-c225t-45f78b8fb67df46f666dd7dc9d447c9e4389a955eb1a71ab8173b5632a5c569d3</cites><orcidid>0000-0003-4448-9082 ; 0009-0002-0097-5169 ; 0000-0001-5123-5756</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38439668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reinseth, Ingvild</creatorcontrib><creatorcontrib>Diep, Dzung B</creatorcontrib><creatorcontrib>Kjos, Morten</creatorcontrib><creatorcontrib>Tønnesen, Hanne H</creatorcontrib><creatorcontrib>Carlsen, Harald</creatorcontrib><title>Exploring the feasibility of bacteriocins EntK1 and EntEJ97s in treatment of systemic vancomycin resistant enterococci infections in mice</title><title>Journal of applied microbiology</title><addtitle>J Appl Microbiol</addtitle><description>Enterocins K1 and EJ97 have specific antimicrobial activity against Enterococcus faecium and Enterococcus faecalis, respectively. The aim of this study was to investigate the utility of these enterocins for in vivo treatment of systemic enterococcal infections.
The antimicrobial effect in blood was analysed and compared against the effect in saline. Colony forming unit counts revealed that the enterocins killed all the bacteria within 1 hour. Additionally, the bactericidal effect against E. faecalis was more rapid in blood, indicating a possible synergy between EntEJ97 and blood. Importantly, no enterocin resistant mutants emerged in these experiments. Injecting the enterocins intraperitoneally in an in vivo mouse model and using fluorescence and minimum inhibitory concentration determination to estimate concentrations of the peptides in plasma, indicate that the enterocins exist in circulation in therapeutic concentrations. Alanine aminotransferase detection, and haemolysis analysis indicates that there is no detectable liver damage or haemolytic effect after injection.
The study revealed that EntK1 and EntEJ97 are able to kill all bacteria ex vivo in the presence of blood. In vivo experiments determine that the enterocins exist in circulation in therapeutic concentrations without causing liver damage or haemolysis. Future experiments should test these peptides for treatment of infection in a relevant in vivo model.</description><issn>1365-2672</issn><issn>1365-2672</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpNkDtPBCEURonR-G4tDaXNKgwDDKUx6zux0XoCzEUxM7ACa3Z_gv_aWXc1VvcW53zFQeiEknNKFLt414Px8aJfaCC83kL7lAk-qYSstv_9e-gg53dCKCNc7KI91tRMCdHso6_pYtbH5MMrLm-AHejsje99WeLosNG2QPLR-pDxNJQHinXoVt_0XsmMfcAlgS4DhLLi8zIXGLzFnzrYOCxHDyfIPhc9AiMEKdporR9NB7b4GH5GRgWO0I7TfYbjzT1EL9fT56vbyePTzd3V5ePEVhUvk5o72ZjGGSE7VwsnhOg62VnV1bW0CmrWKK04B0O1pNo0VDLDBas0t1yojh2is_XuLMWPOeTSDj5b6HsdIM5zWykmJRGEkhE9X6M2xZwTuHaW_KDTsqWkXeVv1_nbTf5RON1sz80A3R_-25t9A8V-hgc</recordid><startdate>20240301</startdate><enddate>20240301</enddate><creator>Reinseth, Ingvild</creator><creator>Diep, Dzung B</creator><creator>Kjos, Morten</creator><creator>Tønnesen, Hanne H</creator><creator>Carlsen, Harald</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4448-9082</orcidid><orcidid>https://orcid.org/0009-0002-0097-5169</orcidid><orcidid>https://orcid.org/0000-0001-5123-5756</orcidid></search><sort><creationdate>20240301</creationdate><title>Exploring the feasibility of bacteriocins EntK1 and EntEJ97s in treatment of systemic vancomycin resistant enterococci infections in mice</title><author>Reinseth, Ingvild ; Diep, Dzung B ; Kjos, Morten ; Tønnesen, Hanne H ; Carlsen, Harald</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c225t-45f78b8fb67df46f666dd7dc9d447c9e4389a955eb1a71ab8173b5632a5c569d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reinseth, Ingvild</creatorcontrib><creatorcontrib>Diep, Dzung B</creatorcontrib><creatorcontrib>Kjos, Morten</creatorcontrib><creatorcontrib>Tønnesen, Hanne H</creatorcontrib><creatorcontrib>Carlsen, Harald</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of applied microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reinseth, Ingvild</au><au>Diep, Dzung B</au><au>Kjos, Morten</au><au>Tønnesen, Hanne H</au><au>Carlsen, Harald</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring the feasibility of bacteriocins EntK1 and EntEJ97s in treatment of systemic vancomycin resistant enterococci infections in mice</atitle><jtitle>Journal of applied microbiology</jtitle><addtitle>J Appl Microbiol</addtitle><date>2024-03-01</date><risdate>2024</risdate><volume>135</volume><issue>3</issue><issn>1365-2672</issn><eissn>1365-2672</eissn><abstract>Enterocins K1 and EJ97 have specific antimicrobial activity against Enterococcus faecium and Enterococcus faecalis, respectively. The aim of this study was to investigate the utility of these enterocins for in vivo treatment of systemic enterococcal infections.
The antimicrobial effect in blood was analysed and compared against the effect in saline. Colony forming unit counts revealed that the enterocins killed all the bacteria within 1 hour. Additionally, the bactericidal effect against E. faecalis was more rapid in blood, indicating a possible synergy between EntEJ97 and blood. Importantly, no enterocin resistant mutants emerged in these experiments. Injecting the enterocins intraperitoneally in an in vivo mouse model and using fluorescence and minimum inhibitory concentration determination to estimate concentrations of the peptides in plasma, indicate that the enterocins exist in circulation in therapeutic concentrations. Alanine aminotransferase detection, and haemolysis analysis indicates that there is no detectable liver damage or haemolytic effect after injection.
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title | Exploring the feasibility of bacteriocins EntK1 and EntEJ97s in treatment of systemic vancomycin resistant enterococci infections in mice |
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