This title appears in the Scientific Report :
2005
Please use the identifier:
http://dx.doi.org/10.1099/mic.0.27804-0 in citations.
Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum
Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum
Corynebacterium glutamicum is used for the large-scale production of L-glutamate, but the efflux of this amino acid is poorly understood. This study shows that addition of ethambutol (EMB) to growing cultures of C. glutamicum causes L-glutamate efflux at rates of up to 15 nmol min(-1) (mg dry wt)(-1...
Saved in:
Personal Name(s): | Radmacher, E. |
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Stansen, K. C. / Besra, N. A. M. / Alderwick, L. J. / Maughan, W. N. / Hollweg, G. / Sahm, H. / Wendisch, V. F. / Eggeling, L. | |
Contributing Institute: |
Biotechnologie 1; IBT-1 |
Published in: | Microbiology, 151 (2005) S. 1359 - 1368 |
Imprint: |
Reading
Soc.
2005
|
Physical Description: |
1359 - 1368 |
DOI: |
10.1099/mic.0.27804-0 |
PubMed ID: |
15870446 |
Document Type: |
Journal Article |
Research Program: |
Biotechnologie |
Series Title: |
Microbiology
151 |
Subject (ZB): | |
Publikationsportal JuSER |
Corynebacterium glutamicum is used for the large-scale production of L-glutamate, but the efflux of this amino acid is poorly understood. This study shows that addition of ethambutol (EMB) to growing cultures of C. glutamicum causes L-glutamate efflux at rates of up to 15 nmol min(-1) (mg dry wt)(-1), whereas in the absence of EMB, no efflux occurs. EMB is used for the treatment of Mycobacterium tuberculosis, and at a molecular level it targets a series of arabinosyltransferases (EmbCAB). The single arabinosyltransferase-encoding emb gene of C. glutamicum was placed under the control of a Tet repressor (TetR). Experiments with this strain, as well as with an emb-overexpressing strain, coupled with biochemical analyses showed that: (i) emb expression was correlated with L-glutamate efflux, (ii) emb overexpression increased EMB resistance, (iii) EMB caused less arabinan deposition in cell wall arabinogalactan, and (iv) EMB caused a reduced content of cell-wall-bound mycolic acids. Thus EMB addition resulted in a marked disordering of the cell envelope, which was also discernible by examining cellular morphology. In order to further characterize the cellular response to EMB addition, genome-wide expression profiling was performed using DNA microarrays. This identified 76 differentially expressed genes, with 18 of them upregulated more than eightfold. Among these were the cell-wall-related genes ftsE and mepA (encoding a secreted metalloprotease); however, genes of central metabolism were largely absent. Given that an altered lipid composition of the plasma membrane of C. glutamicum can result in L-glutamate efflux, we speculate that major structural alterations of the cell envelope are transmitted to the membrane, which in turn activates an export system, perhaps via increased membrane tension. |