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dc.contributor.authorFerrer-Espada, Raquel
dc.contributor.authorShahrour, Hawraa
dc.contributor.authorPitts, Betsey
dc.contributor.authorStewart, Philip S.
dc.contributor.authorSánchez-Gómez, Susana
dc.contributor.authorMartínez-de-Tejada, Guillermo
dc.date.accessioned2019-04-04T22:58:22Z
dc.date.available2019-04-04T22:58:22Z
dc.date.issued2019-03
dc.identifier.citationFerrer-Espada, Raquel, Hawraa Shahrour, Betsey Pitts, Philip S. Stewart, Susana Sánchez-Gómez, and Guillermo Martínez-de-Tejada. “A Permeability-Increasing Drug Synergizes with Bacterial Efflux Pump Inhibitors and Restores Susceptibility to Antibiotics in Multi-Drug Resistant Pseudomonas Aeruginosa Strains.” Scientific Reports 9, no. 1 (March 5, 2019). doi:10.1038/s41598-019-39659-4.en_US
dc.identifier.issn2045-2322
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15407
dc.description.abstractResistance 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.en_US
dc.description.sponsorshipEusko Jaurlaritza (BFI-2011-9)en_US
dc.language.isoenen_US
dc.rightsCC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleA permeability-increasing drug synergizes with bacterial efflux pump inhibitors and restores susceptibility to antibiotics in multi-drug resistant Pseudomonas aeruginosa strainsen_US
dc.typeArticleen_US
mus.citation.extentfirstpage3452en_US
mus.citation.issue1en_US
mus.citation.journaltitleScientific Reportsen_US
mus.citation.volume9en_US
mus.identifier.categoryEngineering & Computer Scienceen_US
mus.identifier.doi10.1038/s41598-019-39659-4en_US
mus.relation.collegeCollege of Engineeringen_US
mus.relation.departmentCenter for Biofilm Engineering.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.relation.researchgroupCenter for Biofilm Engineering.en_US
mus.data.thumbpage7en_US


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CC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.
Except where otherwise noted, this item's license is described as CC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.