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http://purl.uniprot.org/citations/16373429http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16373429http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16373429http://www.w3.org/2000/01/rdf-schema#comment"

Objectives

The aim of this study was to characterize the efflux pump Tap from Mycobacterium fortuitum, to test its sensitivity to well known efflux inhibitors, to study the interaction between tetracycline and these compounds and to test the ability of these compounds to overcome efflux pump-mediated tetracycline resistance. For all these studies, we produced Tap protein in Mycobacterium smegmatis.

Methods

Antibiotic susceptibility tests, tetracycline uptake/efflux experiments and checkerboard synergy tests.

Results

Tetracycline uptake/efflux experiments showed that Tap protein from M. fortuitum uses the electrochemical gradient across the cytoplasmic membrane to extrude tetracycline from the cell. This efflux activity is inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP) and reserpine, consistent with the decrease in MIC observed in antibiotic susceptibility testing in the presence of these inhibitors. Accumulation was not inhibited in experiments in which o-vanadate and chlorpromazine (CPZ) were tested. Inhibitor-treated cells used glycerol as a carbon source to re-establish the electrochemical gradient across the membrane and to restore efflux activity. CCCP, reserpine and CPZ reduced the MIC of tetracycline in the M. smegmatis strain expressing the Tap protein, whereas o-vanadate increased the MIC. We also observed synergy between tetracycline and CPZ or reserpine, and antagonism with o-vanadate.

Conclusions

The Tapfor efflux pump uses the electrochemical gradient to extrude tetracycline from the cell. This efflux activity can be inhibited by several compounds. This suggests that similar compounds could be used to overcome antibiotic resistance mediated by efflux pumps."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.org/dc/terms/identifier"doi:10.1093/jac/dki436"xsd:string
http://purl.uniprot.org/citations/16373429http://purl.org/dc/terms/identifier"doi:10.1093/jac/dki436"xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/author"Martin C."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/author"Martin C."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/author"Ainsa J.A."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/author"Ainsa J.A."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/author"De Rossi E."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/author"De Rossi E."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/author"Ramon-Garcia S."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/author"Ramon-Garcia S."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/name"J. Antimicrob. Chemother."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/name"J. Antimicrob. Chemother."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/pages"252-259"xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/pages"252-259"xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/title"Characterization of tetracycline resistance mediated by the efflux pump Tap from Mycobacterium fortuitum."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/title"Characterization of tetracycline resistance mediated by the efflux pump Tap from Mycobacterium fortuitum."xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/volume"57"xsd:string
http://purl.uniprot.org/citations/16373429http://purl.uniprot.org/core/volume"57"xsd:string
http://purl.uniprot.org/citations/16373429http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16373429
http://purl.uniprot.org/citations/16373429http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16373429
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