Lytic bacteriophages against multidrug-resistant Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolates from orthopaedic implant-associated infections
•Implant-related infections are a devastating complication of orthopaedic surgery.•The emergence of multidrug-resistant bacteria increases concern for their treatment.•High specificity and effectiveness make phages candidates as an orthopaedic therapeutic.•Isolated phages were efficient in infecting...
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creator | Barros, Joana Melo, Luís D.R. Poeta, Patrícia Igrejas, Gilberto Ferraz, Maria P. Azeredo, Joana Monteiro, Fernando J. |
description | •Implant-related infections are a devastating complication of orthopaedic surgery.•The emergence of multidrug-resistant bacteria increases concern for their treatment.•High specificity and effectiveness make phages candidates as an orthopaedic therapeutic.•Isolated phages were efficient in infecting and reducing multidrug-resistant bacteria.•Phage therapy could be suitable to treat pathogenic bacteria in orthopaedic infections.
Orthopaedic implant-associated infections are a devastating complication of orthopaedic surgery with a significant impact on patients and healthcare systems. The aims of this work were to describe the patterns of antimicrobial resistance, pathogenicity and virulence of clinical bacterial isolates from orthopaedic implant-associated infections and to further isolate and characterise bacteriophages that are efficient in controlling these bacteria. Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolated from orthopaedic infections showed multiresistance patterns to the most frequently used antibiotics in clinical settings. The presence of mobile genetic elements (mecA, Tn916/Tn1545 and intl1) and virulence determinants (icaB, cna, hlb, cylLs, cylM, agg, gelE, fsr and fimA) highlighted the pathogenicity of these isolates. Moreover, the isolates belonged to clonal complexes associated with the acquisition of pathogenicity islands and antimicrobial resistance genes by recombination and horizontal gene transfer. Bacteriophages vB_SauM_LM12, vB_EfaS_LM99 and vB_EcoM_JB75 were characterised and their ability to infect clinical isolates of S. aureus, E. faecalis and E. coli, respectively, was assessed. Morphological and genomic analyses revealed that vB_EfaS_LM99 and vB_EcoM_JB75 belong to the Siphoviridae and Myoviridae families, respectively, and no genes associated with lysogeny were found. The bacteriophages showed low latent periods, high burst sizes, broad host ranges and tolerance to several environmental conditions. Moreover, they showed high efficiency and specificity to infect and reduce clinical bacteria, including methicillin-resistant S. aureus and vancomycin-resistant enterococci. Therefore, the results obtained suggest that the bacteriophages used in this work are a promising approach to control these pathogens involved in orthopaedic implant-associated infections. |
doi_str_mv | 10.1016/j.ijantimicag.2019.06.007 |
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Orthopaedic implant-associated infections are a devastating complication of orthopaedic surgery with a significant impact on patients and healthcare systems. The aims of this work were to describe the patterns of antimicrobial resistance, pathogenicity and virulence of clinical bacterial isolates from orthopaedic implant-associated infections and to further isolate and characterise bacteriophages that are efficient in controlling these bacteria. Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolated from orthopaedic infections showed multiresistance patterns to the most frequently used antibiotics in clinical settings. The presence of mobile genetic elements (mecA, Tn916/Tn1545 and intl1) and virulence determinants (icaB, cna, hlb, cylLs, cylM, agg, gelE, fsr and fimA) highlighted the pathogenicity of these isolates. Moreover, the isolates belonged to clonal complexes associated with the acquisition of pathogenicity islands and antimicrobial resistance genes by recombination and horizontal gene transfer. Bacteriophages vB_SauM_LM12, vB_EfaS_LM99 and vB_EcoM_JB75 were characterised and their ability to infect clinical isolates of S. aureus, E. faecalis and E. coli, respectively, was assessed. Morphological and genomic analyses revealed that vB_EfaS_LM99 and vB_EcoM_JB75 belong to the Siphoviridae and Myoviridae families, respectively, and no genes associated with lysogeny were found. The bacteriophages showed low latent periods, high burst sizes, broad host ranges and tolerance to several environmental conditions. Moreover, they showed high efficiency and specificity to infect and reduce clinical bacteria, including methicillin-resistant S. aureus and vancomycin-resistant enterococci. Therefore, the results obtained suggest that the bacteriophages used in this work are a promising approach to control these pathogens involved in orthopaedic implant-associated infections.</description><identifier>ISSN: 0924-8579</identifier><identifier>EISSN: 1872-7913</identifier><identifier>DOI: 10.1016/j.ijantimicag.2019.06.007</identifier><identifier>PMID: 31229670</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Bacteriolysis ; Bacteriophages - growth & development ; Bacteriophages - isolation & purification ; Drug Resistance, Multiple, Bacterial ; Efficiency ; Enterococcus faecalis - drug effects ; Enterococcus faecalis - isolation & purification ; Enterococcus faecalis - pathogenicity ; Enterococcus faecalis - virology ; Escherichia coli - drug effects ; Escherichia coli - isolation & purification ; Escherichia coli - pathogenicity ; Escherichia coli - virology ; Escherichia coli Infections - therapy ; Female ; Gram-Positive Bacterial Infections - microbiology ; Gram-Positive Bacterial Infections - therapy ; Humans ; Implant-associated infection ; Male ; Middle Aged ; Multidrug resistance ; Orthopedic Procedures - adverse effects ; Pathogenic bacteria ; Phage therapy ; Phage Therapy - methods ; Prosthesis-Related Infections - microbiology ; Prosthesis-Related Infections - therapy ; Specificity ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - isolation & purification ; Staphylococcus aureus - pathogenicity ; Staphylococcus aureus - virology</subject><ispartof>International journal of antimicrobial agents, 2019-09, Vol.54 (3), p.329-337</ispartof><rights>2019 Elsevier B.V. and International Society of Chemotherapy</rights><rights>Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-24db66ca089079baf87a69c64bbc548bf7d1ae2d27d4323e863f3246fbf328213</citedby><cites>FETCH-LOGICAL-c453t-24db66ca089079baf87a69c64bbc548bf7d1ae2d27d4323e863f3246fbf328213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijantimicag.2019.06.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27913,27914,45984</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31229670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barros, Joana</creatorcontrib><creatorcontrib>Melo, Luís D.R.</creatorcontrib><creatorcontrib>Poeta, Patrícia</creatorcontrib><creatorcontrib>Igrejas, Gilberto</creatorcontrib><creatorcontrib>Ferraz, Maria P.</creatorcontrib><creatorcontrib>Azeredo, Joana</creatorcontrib><creatorcontrib>Monteiro, Fernando J.</creatorcontrib><title>Lytic bacteriophages against multidrug-resistant Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolates from orthopaedic implant-associated infections</title><title>International journal of antimicrobial agents</title><addtitle>Int J Antimicrob Agents</addtitle><description>•Implant-related infections are a devastating complication of orthopaedic surgery.•The emergence of multidrug-resistant bacteria increases concern for their treatment.•High specificity and effectiveness make phages candidates as an orthopaedic therapeutic.•Isolated phages were efficient in infecting and reducing multidrug-resistant bacteria.•Phage therapy could be suitable to treat pathogenic bacteria in orthopaedic infections.
Orthopaedic implant-associated infections are a devastating complication of orthopaedic surgery with a significant impact on patients and healthcare systems. The aims of this work were to describe the patterns of antimicrobial resistance, pathogenicity and virulence of clinical bacterial isolates from orthopaedic implant-associated infections and to further isolate and characterise bacteriophages that are efficient in controlling these bacteria. Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolated from orthopaedic infections showed multiresistance patterns to the most frequently used antibiotics in clinical settings. The presence of mobile genetic elements (mecA, Tn916/Tn1545 and intl1) and virulence determinants (icaB, cna, hlb, cylLs, cylM, agg, gelE, fsr and fimA) highlighted the pathogenicity of these isolates. Moreover, the isolates belonged to clonal complexes associated with the acquisition of pathogenicity islands and antimicrobial resistance genes by recombination and horizontal gene transfer. Bacteriophages vB_SauM_LM12, vB_EfaS_LM99 and vB_EcoM_JB75 were characterised and their ability to infect clinical isolates of S. aureus, E. faecalis and E. coli, respectively, was assessed. Morphological and genomic analyses revealed that vB_EfaS_LM99 and vB_EcoM_JB75 belong to the Siphoviridae and Myoviridae families, respectively, and no genes associated with lysogeny were found. The bacteriophages showed low latent periods, high burst sizes, broad host ranges and tolerance to several environmental conditions. Moreover, they showed high efficiency and specificity to infect and reduce clinical bacteria, including methicillin-resistant S. aureus and vancomycin-resistant enterococci. Therefore, the results obtained suggest that the bacteriophages used in this work are a promising approach to control these pathogens involved in orthopaedic implant-associated infections.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Bacteriolysis</subject><subject>Bacteriophages - growth & development</subject><subject>Bacteriophages - isolation & purification</subject><subject>Drug Resistance, Multiple, Bacterial</subject><subject>Efficiency</subject><subject>Enterococcus faecalis - drug effects</subject><subject>Enterococcus faecalis - isolation & purification</subject><subject>Enterococcus faecalis - pathogenicity</subject><subject>Enterococcus faecalis - virology</subject><subject>Escherichia coli - drug effects</subject><subject>Escherichia coli - isolation & purification</subject><subject>Escherichia coli - pathogenicity</subject><subject>Escherichia coli - virology</subject><subject>Escherichia coli Infections - therapy</subject><subject>Female</subject><subject>Gram-Positive Bacterial Infections - microbiology</subject><subject>Gram-Positive Bacterial Infections - therapy</subject><subject>Humans</subject><subject>Implant-associated infection</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multidrug resistance</subject><subject>Orthopedic Procedures - adverse effects</subject><subject>Pathogenic bacteria</subject><subject>Phage therapy</subject><subject>Phage Therapy - methods</subject><subject>Prosthesis-Related Infections - microbiology</subject><subject>Prosthesis-Related Infections - therapy</subject><subject>Specificity</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Staphylococcus aureus - isolation & purification</subject><subject>Staphylococcus aureus - pathogenicity</subject><subject>Staphylococcus aureus - virology</subject><issn>0924-8579</issn><issn>1872-7913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcGO0zAQhi0EYsvCKyBz40CC7ThOckRVgZUqcQDOljN2mqmSONgOUl-Jp8Sr7iKOexrJ_ub_Z-Yn5B1nJWdcfTyXeDZLwhnBnErBeFcyVTLWPCM73jaiaDpePSc71glZtHXT3ZBXMZ4Z43Ul65fkpuJCdKphO_LneEkItDeQXEC_jubkIjUng0tMdN6mhDZspyK4iDFlU_o9mXW8TB48wJbRLbgtfqCHJQs8Pg7GgZkw_y6WHiKMWRtGNBT8hBSjn0zKNkPwM_UhjX41zuYxcF6n7FGYGD1gZizFZXCQ0C_xNXkxmCm6Nw_1lvz8fPix_1ocv3252386FiDrKhVC2l4pMKztWNP1ZmgbozpQsu-hlm0_NJYbJ6xorKxE5VpVDZWQauhzaQWvbsn7q-4a_K_NxaRnjOCmPJnzW9Qiw6JmQrYZ7a4oBB9jcINeA84mXDRn-j4qfdb_RaXvo9JM6RxV7n37YLP1s7P_Oh-zycD-Cri87G90QUdAt0C-VMgn0dbjE2z-AsR6sT0</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Barros, Joana</creator><creator>Melo, Luís D.R.</creator><creator>Poeta, Patrícia</creator><creator>Igrejas, Gilberto</creator><creator>Ferraz, Maria P.</creator><creator>Azeredo, Joana</creator><creator>Monteiro, Fernando J.</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20190901</creationdate><title>Lytic bacteriophages against multidrug-resistant Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolates from orthopaedic implant-associated infections</title><author>Barros, Joana ; Melo, Luís D.R. ; Poeta, Patrícia ; Igrejas, Gilberto ; Ferraz, Maria P. ; Azeredo, Joana ; Monteiro, Fernando J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-24db66ca089079baf87a69c64bbc548bf7d1ae2d27d4323e863f3246fbf328213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Bacteriolysis</topic><topic>Bacteriophages - growth & development</topic><topic>Bacteriophages - isolation & purification</topic><topic>Drug Resistance, Multiple, Bacterial</topic><topic>Efficiency</topic><topic>Enterococcus faecalis - drug effects</topic><topic>Enterococcus faecalis - isolation & purification</topic><topic>Enterococcus faecalis - pathogenicity</topic><topic>Enterococcus faecalis - virology</topic><topic>Escherichia coli - drug effects</topic><topic>Escherichia coli - isolation & purification</topic><topic>Escherichia coli - pathogenicity</topic><topic>Escherichia coli - virology</topic><topic>Escherichia coli Infections - therapy</topic><topic>Female</topic><topic>Gram-Positive Bacterial Infections - microbiology</topic><topic>Gram-Positive Bacterial Infections - therapy</topic><topic>Humans</topic><topic>Implant-associated infection</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multidrug resistance</topic><topic>Orthopedic Procedures - adverse effects</topic><topic>Pathogenic bacteria</topic><topic>Phage therapy</topic><topic>Phage Therapy - methods</topic><topic>Prosthesis-Related Infections - microbiology</topic><topic>Prosthesis-Related Infections - therapy</topic><topic>Specificity</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Staphylococcus aureus - isolation & purification</topic><topic>Staphylococcus aureus - pathogenicity</topic><topic>Staphylococcus aureus - virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barros, Joana</creatorcontrib><creatorcontrib>Melo, Luís D.R.</creatorcontrib><creatorcontrib>Poeta, Patrícia</creatorcontrib><creatorcontrib>Igrejas, Gilberto</creatorcontrib><creatorcontrib>Ferraz, Maria P.</creatorcontrib><creatorcontrib>Azeredo, Joana</creatorcontrib><creatorcontrib>Monteiro, Fernando J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of antimicrobial agents</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barros, Joana</au><au>Melo, Luís D.R.</au><au>Poeta, Patrícia</au><au>Igrejas, Gilberto</au><au>Ferraz, Maria P.</au><au>Azeredo, Joana</au><au>Monteiro, Fernando J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lytic bacteriophages against multidrug-resistant Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolates from orthopaedic implant-associated infections</atitle><jtitle>International journal of antimicrobial agents</jtitle><addtitle>Int J Antimicrob Agents</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>54</volume><issue>3</issue><spage>329</spage><epage>337</epage><pages>329-337</pages><issn>0924-8579</issn><eissn>1872-7913</eissn><abstract>•Implant-related infections are a devastating complication of orthopaedic surgery.•The emergence of multidrug-resistant bacteria increases concern for their treatment.•High specificity and effectiveness make phages candidates as an orthopaedic therapeutic.•Isolated phages were efficient in infecting and reducing multidrug-resistant bacteria.•Phage therapy could be suitable to treat pathogenic bacteria in orthopaedic infections.
Orthopaedic implant-associated infections are a devastating complication of orthopaedic surgery with a significant impact on patients and healthcare systems. The aims of this work were to describe the patterns of antimicrobial resistance, pathogenicity and virulence of clinical bacterial isolates from orthopaedic implant-associated infections and to further isolate and characterise bacteriophages that are efficient in controlling these bacteria. Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolated from orthopaedic infections showed multiresistance patterns to the most frequently used antibiotics in clinical settings. The presence of mobile genetic elements (mecA, Tn916/Tn1545 and intl1) and virulence determinants (icaB, cna, hlb, cylLs, cylM, agg, gelE, fsr and fimA) highlighted the pathogenicity of these isolates. Moreover, the isolates belonged to clonal complexes associated with the acquisition of pathogenicity islands and antimicrobial resistance genes by recombination and horizontal gene transfer. Bacteriophages vB_SauM_LM12, vB_EfaS_LM99 and vB_EcoM_JB75 were characterised and their ability to infect clinical isolates of S. aureus, E. faecalis and E. coli, respectively, was assessed. Morphological and genomic analyses revealed that vB_EfaS_LM99 and vB_EcoM_JB75 belong to the Siphoviridae and Myoviridae families, respectively, and no genes associated with lysogeny were found. The bacteriophages showed low latent periods, high burst sizes, broad host ranges and tolerance to several environmental conditions. Moreover, they showed high efficiency and specificity to infect and reduce clinical bacteria, including methicillin-resistant S. aureus and vancomycin-resistant enterococci. Therefore, the results obtained suggest that the bacteriophages used in this work are a promising approach to control these pathogens involved in orthopaedic implant-associated infections.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31229670</pmid><doi>10.1016/j.ijantimicag.2019.06.007</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Aged, 80 and over Bacteriolysis Bacteriophages - growth & development Bacteriophages - isolation & purification Drug Resistance, Multiple, Bacterial Efficiency Enterococcus faecalis - drug effects Enterococcus faecalis - isolation & purification Enterococcus faecalis - pathogenicity Enterococcus faecalis - virology Escherichia coli - drug effects Escherichia coli - isolation & purification Escherichia coli - pathogenicity Escherichia coli - virology Escherichia coli Infections - therapy Female Gram-Positive Bacterial Infections - microbiology Gram-Positive Bacterial Infections - therapy Humans Implant-associated infection Male Middle Aged Multidrug resistance Orthopedic Procedures - adverse effects Pathogenic bacteria Phage therapy Phage Therapy - methods Prosthesis-Related Infections - microbiology Prosthesis-Related Infections - therapy Specificity Staphylococcus aureus - drug effects Staphylococcus aureus - isolation & purification Staphylococcus aureus - pathogenicity Staphylococcus aureus - virology |
title | Lytic bacteriophages against multidrug-resistant Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolates from orthopaedic implant-associated infections |
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