A permeability-increasing drug synergizes with bacterial efflux pump inhibitors and restores susceptibility to antibiotics in multi-drug resistant Pseudomonas aeruginosa strains View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Raquel Ferrer-Espada, Hawraa Shahrour, Betsey Pitts, Philip S. Stewart, Susana Sánchez-Gómez, Guillermo Martínez-de-Tejada

ABSTRACT

Resistance to antibiotics poses a major global threat according to the World Health Organization. Restoring the activity of existing drugs is an attractive alternative to address this challenge. One of the most efficient mechanisms of bacterial resistance involves the expression of efflux pump systems capable of expelling antibiotics from the cell. Although there are efflux pump inhibitors (EPIs) available, these molecules are toxic for humans. We hypothesized that permeability-increasing antimicrobial peptides (AMPs) could lower the amount of EPI necessary to sensitize bacteria to antibiotics that are efflux substrates. To test this hypothesis, we measured the ability of polymyxin B nonapeptide (PMBN), to synergize with antibiotics in the presence of EPIs. Assays were performed using planktonic and biofilm-forming cells of Pseudomonas aeruginosa strains overexpressing the MexAB-OprM efflux system. Synergy between PMBN and EPIs boosted azithromycin activity by a factor of 2,133 and sensitized P. aeruginosa to all tested antibiotics. This reduced several orders of magnitude the amount of inhibitor needed for antibiotic sensitization. The selected antibiotic-EPI-PMBN combination caused a 10 million-fold reduction in the viability of biofilm forming cells. We proved that AMPs can synergize with EPIs and that this phenomenon can be exploited to sensitize bacteria to antibiotics. More... »

PAGES

3452

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-39659-4

DOI

http://dx.doi.org/10.1038/s41598-019-39659-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112543981

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30837499


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1108", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical Microbiology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Navarra", 
          "id": "https://www.grid.ac/institutes/grid.5924.a", 
          "name": [
            "University of Navarra, Department of Microbiology and Parasitology, Irunlarrea 1, 31008, Pamplona, Spain", 
            "Navarra Institute for Health Research (IdiSNA), Pamplona, Spain", 
            "Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, 02114, Boston, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ferrer-Espada", 
        "givenName": "Raquel", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Lebanese University", 
          "id": "https://www.grid.ac/institutes/grid.411324.1", 
          "name": [
            "University of Navarra, Department of Microbiology and Parasitology, Irunlarrea 1, 31008, Pamplona, Spain", 
            "Navarra Institute for Health Research (IdiSNA), Pamplona, Spain", 
            "Laboratory of Microbiology, Department of Life & Earth Sciences, Faculty of Sciences I, Lebanese University, Hadat campus, Beirut, Lebanon", 
            "Platform of Research and Analysis in Environmental Sciences (PRASE), Doctoral School of Sciences and Technologies, Lebanese University, Hadat campus, Beirut, Lebanon"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shahrour", 
        "givenName": "Hawraa", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Montana State University", 
          "id": "https://www.grid.ac/institutes/grid.41891.35", 
          "name": [
            "Center for Biofilm Engineering, Montana State University, Bozeman, MT, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Pitts", 
        "givenName": "Betsey", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Montana State University", 
          "id": "https://www.grid.ac/institutes/grid.41891.35", 
          "name": [
            "Center for Biofilm Engineering, Montana State University, Bozeman, MT, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Stewart", 
        "givenName": "Philip S.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Bionanoplus S.L. Pol\u00edgono Mochol\u00ed, Plaza Cein N\u00b05, nave B14, 31110, Navarra, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "S\u00e1nchez-G\u00f3mez", 
        "givenName": "Susana", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Navarra", 
          "id": "https://www.grid.ac/institutes/grid.5924.a", 
          "name": [
            "University of Navarra, Department of Microbiology and Parasitology, Irunlarrea 1, 31008, Pamplona, Spain", 
            "Navarra Institute for Health Research (IdiSNA), Pamplona, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mart\u00ednez-de-Tejada", 
        "givenName": "Guillermo", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1128/aac.49.9.3858-3867.2005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003051256"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mmbr.00013-14", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003063298"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bbapap.2008.11.005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005051577"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/acs.chemrestox.5b00262", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005244199"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.00904-10", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005432337"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/cmr.00117-14", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006868674"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.45.6.1930-1933.2001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008307766"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/toxsci/kft247", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009060549"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1378/chest.128.2.912", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011134849"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1378/chest.128.2.912", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011134849"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jac/dkg397", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011613070"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00253-010-2748-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012947035", 
          "https://doi.org/10.1007/s00253-010-2748-3"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00253-010-2748-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012947035", 
          "https://doi.org/10.1007/s00253-010-2748-3"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jac/dkl081", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014978841"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/cmr.00043-12", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016255794"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.01645-10", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017758354"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.44.12.3322-3327.2000", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019019171"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jac/dki445", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020388226"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aem.00142-06", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021834104"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2323/jgam.60.163", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026384034"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3389/fmicb.2011.00065", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027273686"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s12866-015-0473-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027491908", 
          "https://doi.org/10.1186/s12866-015-0473-x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s12866-015-0473-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027491908", 
          "https://doi.org/10.1186/s12866-015-0473-x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0167-7012(00)00122-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027523355"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0063158", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027778720"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1476-5381.2011.01250.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028058539"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.50.4.1463-1469.2006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029026527"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bcp.2005.12.008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030245238"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.49.8.3122-3128.2005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030458919"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.25.6.701", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031884402"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0126479", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032638699"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0060666", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034451364"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.01476-15", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034485083"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.00092-15", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036246817"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/00021369.1973.10861030", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036742943"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.45.1.105-116.2001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038015779"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.49.2.849-852.2005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039127802"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/08927019409378264", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039286372"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/17460441.2012.688949", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039564643"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.01011-06", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039938701"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.03283-14", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040390477"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/cmr.00068-09", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040793636"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jb.02456-14", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045670428"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2180-8-196", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045776224", 
          "https://doi.org/10.1186/1471-2180-8-196"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aem.01310-08", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046168419"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jac/10.4.259", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048000912"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0924-8579(03)00119-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051358309"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0924-8579(03)00119-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051358309"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.45.6.1761-1770.2001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052543875"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/infdis/137.2.122", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059696716"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1586/14787210.2014.863148", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1068078938"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/138161211795703726", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069167677"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/157489106777452692", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069216768"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083237240", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3389/fcimb.2017.00039", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1083824090"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-12", 
    "datePublishedReg": "2019-12-01", 
    "description": "Resistance to antibiotics poses a major global threat according to the World Health Organization. Restoring the activity of existing drugs is an attractive alternative to address this challenge. One of the most efficient mechanisms of bacterial resistance involves the expression of efflux pump systems capable of expelling antibiotics from the cell. Although there are efflux pump inhibitors (EPIs) available, these molecules are toxic for humans. We hypothesized that permeability-increasing antimicrobial peptides (AMPs) could lower the amount of EPI necessary to sensitize bacteria to antibiotics that are efflux substrates. To test this hypothesis, we measured the ability of polymyxin B nonapeptide (PMBN), to synergize with antibiotics in the presence of EPIs. Assays were performed using planktonic and biofilm-forming cells of Pseudomonas aeruginosa strains overexpressing the MexAB-OprM efflux system. Synergy between PMBN and EPIs boosted azithromycin activity by a factor of 2,133 and sensitized P. aeruginosa to all tested antibiotics. This reduced several orders of magnitude the amount of inhibitor needed for antibiotic sensitization. The selected antibiotic-EPI-PMBN combination caused a 10 million-fold reduction in the viability of biofilm forming cells. We proved that AMPs can synergize with EPIs and that this phenomenon can be exploited to sensitize bacteria to antibiotics.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41598-019-39659-4", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1045337", 
        "issn": [
          "2045-2322"
        ], 
        "name": "Scientific Reports", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "9"
      }
    ], 
    "name": "A permeability-increasing drug synergizes with bacterial efflux pump inhibitors and restores susceptibility to antibiotics in multi-drug resistant Pseudomonas aeruginosa strains", 
    "pagination": "3452", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "600c2ea19cf6751fd6bde1b8afb02002c05a6be2d4b9e202bc6084cb319b5c2c"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30837499"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101563288"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41598-019-39659-4"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1112543981"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41598-019-39659-4", 
      "https://app.dimensions.ai/details/publication/pub.1112543981"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T11:17", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000354_0000000354/records_11698_00000002.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s41598-019-39659-4"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39659-4'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39659-4'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39659-4'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39659-4'


 

This table displays all metadata directly associated to this object as RDF triples.

265 TRIPLES      21 PREDICATES      80 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41598-019-39659-4 schema:about anzsrc-for:11
2 anzsrc-for:1108
3 schema:author N181a11966c24424780853c950df1038f
4 schema:citation sg:pub.10.1007/s00253-010-2748-3
5 sg:pub.10.1186/1471-2180-8-196
6 sg:pub.10.1186/s12866-015-0473-x
7 https://app.dimensions.ai/details/publication/pub.1083237240
8 https://doi.org/10.1016/j.bbapap.2008.11.005
9 https://doi.org/10.1016/j.bcp.2005.12.008
10 https://doi.org/10.1016/s0167-7012(00)00122-6
11 https://doi.org/10.1016/s0924-8579(03)00119-5
12 https://doi.org/10.1021/acs.chemrestox.5b00262
13 https://doi.org/10.1080/00021369.1973.10861030
14 https://doi.org/10.1080/08927019409378264
15 https://doi.org/10.1093/infdis/137.2.122
16 https://doi.org/10.1093/jac/10.4.259
17 https://doi.org/10.1093/jac/dkg397
18 https://doi.org/10.1093/jac/dki445
19 https://doi.org/10.1093/jac/dkl081
20 https://doi.org/10.1093/toxsci/kft247
21 https://doi.org/10.1111/j.1476-5381.2011.01250.x
22 https://doi.org/10.1128/aac.00092-15
23 https://doi.org/10.1128/aac.00904-10
24 https://doi.org/10.1128/aac.01011-06
25 https://doi.org/10.1128/aac.01476-15
26 https://doi.org/10.1128/aac.01645-10
27 https://doi.org/10.1128/aac.03283-14
28 https://doi.org/10.1128/aac.25.6.701
29 https://doi.org/10.1128/aac.44.12.3322-3327.2000
30 https://doi.org/10.1128/aac.45.1.105-116.2001
31 https://doi.org/10.1128/aac.45.6.1761-1770.2001
32 https://doi.org/10.1128/aac.45.6.1930-1933.2001
33 https://doi.org/10.1128/aac.49.2.849-852.2005
34 https://doi.org/10.1128/aac.49.8.3122-3128.2005
35 https://doi.org/10.1128/aac.49.9.3858-3867.2005
36 https://doi.org/10.1128/aac.50.4.1463-1469.2006
37 https://doi.org/10.1128/aem.00142-06
38 https://doi.org/10.1128/aem.01310-08
39 https://doi.org/10.1128/cmr.00043-12
40 https://doi.org/10.1128/cmr.00068-09
41 https://doi.org/10.1128/cmr.00117-14
42 https://doi.org/10.1128/jb.02456-14
43 https://doi.org/10.1128/mmbr.00013-14
44 https://doi.org/10.1371/journal.pone.0060666
45 https://doi.org/10.1371/journal.pone.0063158
46 https://doi.org/10.1371/journal.pone.0126479
47 https://doi.org/10.1378/chest.128.2.912
48 https://doi.org/10.1517/17460441.2012.688949
49 https://doi.org/10.1586/14787210.2014.863148
50 https://doi.org/10.2174/138161211795703726
51 https://doi.org/10.2174/157489106777452692
52 https://doi.org/10.2323/jgam.60.163
53 https://doi.org/10.3389/fcimb.2017.00039
54 https://doi.org/10.3389/fmicb.2011.00065
55 schema:datePublished 2019-12
56 schema:datePublishedReg 2019-12-01
57 schema:description Resistance to antibiotics poses a major global threat according to the World Health Organization. Restoring the activity of existing drugs is an attractive alternative to address this challenge. One of the most efficient mechanisms of bacterial resistance involves the expression of efflux pump systems capable of expelling antibiotics from the cell. Although there are efflux pump inhibitors (EPIs) available, these molecules are toxic for humans. We hypothesized that permeability-increasing antimicrobial peptides (AMPs) could lower the amount of EPI necessary to sensitize bacteria to antibiotics that are efflux substrates. To test this hypothesis, we measured the ability of polymyxin B nonapeptide (PMBN), to synergize with antibiotics in the presence of EPIs. Assays were performed using planktonic and biofilm-forming cells of Pseudomonas aeruginosa strains overexpressing the MexAB-OprM efflux system. Synergy between PMBN and EPIs boosted azithromycin activity by a factor of 2,133 and sensitized P. aeruginosa to all tested antibiotics. This reduced several orders of magnitude the amount of inhibitor needed for antibiotic sensitization. The selected antibiotic-EPI-PMBN combination caused a 10 million-fold reduction in the viability of biofilm forming cells. We proved that AMPs can synergize with EPIs and that this phenomenon can be exploited to sensitize bacteria to antibiotics.
58 schema:genre research_article
59 schema:inLanguage en
60 schema:isAccessibleForFree true
61 schema:isPartOf N29d675f30f8c4659bf3e9be93f72dbf4
62 N5148e06f752e450e91fc191b20415d35
63 sg:journal.1045337
64 schema:name A permeability-increasing drug synergizes with bacterial efflux pump inhibitors and restores susceptibility to antibiotics in multi-drug resistant Pseudomonas aeruginosa strains
65 schema:pagination 3452
66 schema:productId N0a3b266ea1bb4388b70ab5494de23f69
67 N715997802ef644408f4577dd6ac5ed57
68 N8200e3fd15ca442b84ca3111d322f40d
69 Nc76392629cd94012a7935d2967585cb5
70 Nf913fc86c0d9475ab51b08f4689c5809
71 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112543981
72 https://doi.org/10.1038/s41598-019-39659-4
73 schema:sdDatePublished 2019-04-11T11:17
74 schema:sdLicense https://scigraph.springernature.com/explorer/license/
75 schema:sdPublisher Nfaf8ab40bf86437899e594502c6fa26f
76 schema:url https://www.nature.com/articles/s41598-019-39659-4
77 sgo:license sg:explorer/license/
78 sgo:sdDataset articles
79 rdf:type schema:ScholarlyArticle
80 N064c426da532422fa519ebc278ea14db schema:affiliation https://www.grid.ac/institutes/grid.41891.35
81 schema:familyName Pitts
82 schema:givenName Betsey
83 rdf:type schema:Person
84 N0a3b266ea1bb4388b70ab5494de23f69 schema:name pubmed_id
85 schema:value 30837499
86 rdf:type schema:PropertyValue
87 N181a11966c24424780853c950df1038f rdf:first Na98b0715c166405e92f64002a1da154d
88 rdf:rest N35755e4b80c640b8bc672b1a2c569754
89 N20c8735eab86458c951fe25ab65037fe schema:affiliation N9bf15911a1b04e4f8ccd050819922f8c
90 schema:familyName Sánchez-Gómez
91 schema:givenName Susana
92 rdf:type schema:Person
93 N2773cd1eb2794c4e81f6eb0327c1a365 schema:affiliation https://www.grid.ac/institutes/grid.5924.a
94 schema:familyName Martínez-de-Tejada
95 schema:givenName Guillermo
96 rdf:type schema:Person
97 N29d675f30f8c4659bf3e9be93f72dbf4 schema:volumeNumber 9
98 rdf:type schema:PublicationVolume
99 N35755e4b80c640b8bc672b1a2c569754 rdf:first N3be7aaadfc04468688cfa30ca36bc636
100 rdf:rest Nd23428d27afb499ebfbdf36f40171e0c
101 N3be7aaadfc04468688cfa30ca36bc636 schema:affiliation https://www.grid.ac/institutes/grid.411324.1
102 schema:familyName Shahrour
103 schema:givenName Hawraa
104 rdf:type schema:Person
105 N4ce3e8f1184149b0881c320d953b39f3 rdf:first Nfeb89a1d61264045a8cc251dab12311b
106 rdf:rest N98e933941a334434ac66502f025f20bf
107 N5148e06f752e450e91fc191b20415d35 schema:issueNumber 1
108 rdf:type schema:PublicationIssue
109 N715997802ef644408f4577dd6ac5ed57 schema:name nlm_unique_id
110 schema:value 101563288
111 rdf:type schema:PropertyValue
112 N8200e3fd15ca442b84ca3111d322f40d schema:name doi
113 schema:value 10.1038/s41598-019-39659-4
114 rdf:type schema:PropertyValue
115 N98e933941a334434ac66502f025f20bf rdf:first N20c8735eab86458c951fe25ab65037fe
116 rdf:rest Nf4c4176f1745431187ae313337810d1d
117 N9bf15911a1b04e4f8ccd050819922f8c schema:name Bionanoplus S.L. Polígono Mocholí, Plaza Cein N°5, nave B14, 31110, Navarra, Spain
118 rdf:type schema:Organization
119 Na98b0715c166405e92f64002a1da154d schema:affiliation https://www.grid.ac/institutes/grid.5924.a
120 schema:familyName Ferrer-Espada
121 schema:givenName Raquel
122 rdf:type schema:Person
123 Nc76392629cd94012a7935d2967585cb5 schema:name readcube_id
124 schema:value 600c2ea19cf6751fd6bde1b8afb02002c05a6be2d4b9e202bc6084cb319b5c2c
125 rdf:type schema:PropertyValue
126 Nd23428d27afb499ebfbdf36f40171e0c rdf:first N064c426da532422fa519ebc278ea14db
127 rdf:rest N4ce3e8f1184149b0881c320d953b39f3
128 Nf4c4176f1745431187ae313337810d1d rdf:first N2773cd1eb2794c4e81f6eb0327c1a365
129 rdf:rest rdf:nil
130 Nf913fc86c0d9475ab51b08f4689c5809 schema:name dimensions_id
131 schema:value pub.1112543981
132 rdf:type schema:PropertyValue
133 Nfaf8ab40bf86437899e594502c6fa26f schema:name Springer Nature - SN SciGraph project
134 rdf:type schema:Organization
135 Nfeb89a1d61264045a8cc251dab12311b schema:affiliation https://www.grid.ac/institutes/grid.41891.35
136 schema:familyName Stewart
137 schema:givenName Philip S.
138 rdf:type schema:Person
139 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
140 schema:name Medical and Health Sciences
141 rdf:type schema:DefinedTerm
142 anzsrc-for:1108 schema:inDefinedTermSet anzsrc-for:
143 schema:name Medical Microbiology
144 rdf:type schema:DefinedTerm
145 sg:journal.1045337 schema:issn 2045-2322
146 schema:name Scientific Reports
147 rdf:type schema:Periodical
148 sg:pub.10.1007/s00253-010-2748-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012947035
149 https://doi.org/10.1007/s00253-010-2748-3
150 rdf:type schema:CreativeWork
151 sg:pub.10.1186/1471-2180-8-196 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045776224
152 https://doi.org/10.1186/1471-2180-8-196
153 rdf:type schema:CreativeWork
154 sg:pub.10.1186/s12866-015-0473-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1027491908
155 https://doi.org/10.1186/s12866-015-0473-x
156 rdf:type schema:CreativeWork
157 https://app.dimensions.ai/details/publication/pub.1083237240 schema:CreativeWork
158 https://doi.org/10.1016/j.bbapap.2008.11.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005051577
159 rdf:type schema:CreativeWork
160 https://doi.org/10.1016/j.bcp.2005.12.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030245238
161 rdf:type schema:CreativeWork
162 https://doi.org/10.1016/s0167-7012(00)00122-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027523355
163 rdf:type schema:CreativeWork
164 https://doi.org/10.1016/s0924-8579(03)00119-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051358309
165 rdf:type schema:CreativeWork
166 https://doi.org/10.1021/acs.chemrestox.5b00262 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005244199
167 rdf:type schema:CreativeWork
168 https://doi.org/10.1080/00021369.1973.10861030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036742943
169 rdf:type schema:CreativeWork
170 https://doi.org/10.1080/08927019409378264 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039286372
171 rdf:type schema:CreativeWork
172 https://doi.org/10.1093/infdis/137.2.122 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059696716
173 rdf:type schema:CreativeWork
174 https://doi.org/10.1093/jac/10.4.259 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048000912
175 rdf:type schema:CreativeWork
176 https://doi.org/10.1093/jac/dkg397 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011613070
177 rdf:type schema:CreativeWork
178 https://doi.org/10.1093/jac/dki445 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020388226
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1093/jac/dkl081 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014978841
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1093/toxsci/kft247 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009060549
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1111/j.1476-5381.2011.01250.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1028058539
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1128/aac.00092-15 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036246817
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1128/aac.00904-10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005432337
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1128/aac.01011-06 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039938701
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1128/aac.01476-15 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034485083
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1128/aac.01645-10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017758354
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1128/aac.03283-14 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040390477
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1128/aac.25.6.701 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031884402
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1128/aac.44.12.3322-3327.2000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019019171
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1128/aac.45.1.105-116.2001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038015779
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1128/aac.45.6.1761-1770.2001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052543875
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1128/aac.45.6.1930-1933.2001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008307766
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1128/aac.49.2.849-852.2005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039127802
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1128/aac.49.8.3122-3128.2005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030458919
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1128/aac.49.9.3858-3867.2005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003051256
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1128/aac.50.4.1463-1469.2006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029026527
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1128/aem.00142-06 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021834104
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1128/aem.01310-08 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046168419
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1128/cmr.00043-12 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016255794
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1128/cmr.00068-09 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040793636
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1128/cmr.00117-14 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006868674
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1128/jb.02456-14 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045670428
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1128/mmbr.00013-14 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003063298
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1371/journal.pone.0060666 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034451364
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1371/journal.pone.0063158 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027778720
233 rdf:type schema:CreativeWork
234 https://doi.org/10.1371/journal.pone.0126479 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032638699
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1378/chest.128.2.912 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011134849
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1517/17460441.2012.688949 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039564643
239 rdf:type schema:CreativeWork
240 https://doi.org/10.1586/14787210.2014.863148 schema:sameAs https://app.dimensions.ai/details/publication/pub.1068078938
241 rdf:type schema:CreativeWork
242 https://doi.org/10.2174/138161211795703726 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069167677
243 rdf:type schema:CreativeWork
244 https://doi.org/10.2174/157489106777452692 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069216768
245 rdf:type schema:CreativeWork
246 https://doi.org/10.2323/jgam.60.163 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026384034
247 rdf:type schema:CreativeWork
248 https://doi.org/10.3389/fcimb.2017.00039 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083824090
249 rdf:type schema:CreativeWork
250 https://doi.org/10.3389/fmicb.2011.00065 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027273686
251 rdf:type schema:CreativeWork
252 https://www.grid.ac/institutes/grid.411324.1 schema:alternateName Lebanese University
253 schema:name Laboratory of Microbiology, Department of Life & Earth Sciences, Faculty of Sciences I, Lebanese University, Hadat campus, Beirut, Lebanon
254 Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
255 Platform of Research and Analysis in Environmental Sciences (PRASE), Doctoral School of Sciences and Technologies, Lebanese University, Hadat campus, Beirut, Lebanon
256 University of Navarra, Department of Microbiology and Parasitology, Irunlarrea 1, 31008, Pamplona, Spain
257 rdf:type schema:Organization
258 https://www.grid.ac/institutes/grid.41891.35 schema:alternateName Montana State University
259 schema:name Center for Biofilm Engineering, Montana State University, Bozeman, MT, USA
260 rdf:type schema:Organization
261 https://www.grid.ac/institutes/grid.5924.a schema:alternateName University of Navarra
262 schema:name Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
263 University of Navarra, Department of Microbiology and Parasitology, Irunlarrea 1, 31008, Pamplona, Spain
264 Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, 02114, Boston, MA, USA
265 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...