Abstract
The role of clinically important multidrug resistance (MDR) efflux pumps in bacterial resistance to various human antimicrobial peptides (AMPs), including cathelicidin LL-37, the alpha-defensins human neutrophil peptides (HNPs)-1-3 and HD-5 and the beta-defensins hBD-2 and -3, was investigated. AMP susceptibility testing was performed by killing assays and standard minimal inhibitory concentration assays. AMP susceptibility was determined in Escherichia coli and Pseudomonas aeruginosa strains overexpressing resistance-nodulation-cell division (RND)-type pumps AcrAB and MexAB, respectively, and in their pump-deficient parental strains. Furthermore, the impact of a member of the major facilitator (MF) efflux pump family was investigated in Staphylococcus aureus overexpressing NorA and in wild-type strains. The E. coli AcrAB and P. aeruginosa MexAB RND-type efflux pumps as well as the S. aureus NorA MF efflux pump were unable to confer resistance to AMPs. These findings do not support a critical role of MDR efflux pumps in the tested pathogens as a strategy to increase virulence by circumventing the antimicrobial action of innate defence AMPs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimicrobial Cationic Peptides / pharmacology*
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Bacterial Outer Membrane Proteins / biosynthesis
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Bacterial Outer Membrane Proteins / genetics
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Bacterial Outer Membrane Proteins / metabolism
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Drug Resistance, Bacterial*
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Escherichia coli / drug effects*
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Escherichia coli Proteins / biosynthesis
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Gene Deletion
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Gene Dosage
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Humans
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Lipoproteins / biosynthesis
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Membrane Transport Proteins / biosynthesis
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism*
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Microbial Sensitivity Tests
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Microbial Viability
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Multidrug Resistance-Associated Proteins / genetics
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Multidrug Resistance-Associated Proteins / metabolism
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Pseudomonas aeruginosa / drug effects*
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Pseudomonas aeruginosa / genetics
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Pseudomonas aeruginosa / metabolism
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Staphylococcus aureus / drug effects*
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Staphylococcus aureus / genetics
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Staphylococcus aureus / metabolism
Substances
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AcrA protein, E coli
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Antimicrobial Cationic Peptides
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Bacterial Outer Membrane Proteins
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Bacterial Proteins
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Escherichia coli Proteins
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Lipoproteins
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Membrane Transport Proteins
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MexA protein, Pseudomonas aeruginosa
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MexB protein, Pseudomonas aeruginosa
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Multidrug Resistance-Associated Proteins
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NorA protein, Staphylococcus