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PMID: 10692352 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The TetA(K) tetracycline/H(+) antiporter from Staphylococcus aureus: mutagenesis and functional analysis of motif C.

Journal of bacteriology ·Vol. 182 ·No. 6 ·2000-03-00 ·Pages 1492-8

Ginn SL, Brown MH, Skurray RA

Abstract

Conserved motif C, identified within members of the major facilitator superfamily (MFS) of transport proteins that mediate drug export, was examined in the tetracycline resistance efflux protein TetA(K) from Staphylococcus aureus; motif C is contained within transmembrane segment 5. Using site-directed mutagenesis, the importance of the conserved glycine (G151, G155, G159, and G160) and proline (P156) residues within this motif was investigated. Over 40 individual amino acid replacements were introduced; however, only alanine and serine substitutions for glycine at G151, G155, and G160 were found to retain significant levels of tetracycline resistance and transport activity in cells expressing mutant proteins. Notably, P156 and G159 appear to be crucial, as amino acid replacements at these positions either significantly reduced or abolished tetracycline/H(+) activity. The highly conserved nature of motif C and its distribution throughout drug exporters imply that the residues of motif C play a similar role in all MFS proteins that function as antiporters.

MeSH Terms
Amino Acid Motifs/genetics Antiporters/genetics,metabolism Bacterial Proteins/genetics,metabolism Cell Membrane/metabolism Mutagenesis, Site-Directed Staphylococcus aureus/drug effects,genetics,metabolism Tetracycline/metabolism Tetracycline Resistance/genetics
Chemicals
Antiporters Bacterial Proteins tetA protein, Bacteria Tetracycline
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ginn S L
School of Biological Sciences, University of Sydney, Sydney, New South Wales 2006, Australia.
Brown M H
Skurray R A
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.182.6.1492-1498.2000
Published
2000-03-00
Pages
1492-8
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC94444
Subset
IM
External Links
PubMed source DOI: 10.1128/JB.182.6.1492-1498.2000 PMC Full Text View journal details
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