Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum

Radmacher E, Stansen KC, Besra GS, Alderwick LJ, Maughan WN, Hollweg G, Sahm H, Wendisch VF, Eggeling L (2005)
Microbiology-Sgm 151(5): 1359-1368.

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Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
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.
Erscheinungsjahr
Zeitschriftentitel
Microbiology-Sgm
Band
151
Zeitschriftennummer
5
Seite
1359-1368
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Radmacher E, Stansen KC, Besra GS, et al. Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum. Microbiology-Sgm. 2005;151(5):1359-1368.
Radmacher, E., Stansen, K. C., Besra, G. S., Alderwick, L. J., Maughan, W. N., Hollweg, G., Sahm, H., et al. (2005). Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum. Microbiology-Sgm, 151(5), 1359-1368. doi:10.1099/mic.0.27804-0
Radmacher, E., Stansen, K. C., Besra, G. S., Alderwick, L. J., Maughan, W. N., Hollweg, G., Sahm, H., Wendisch, V. F., and Eggeling, L. (2005). Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum. Microbiology-Sgm 151, 1359-1368.
Radmacher, E., et al., 2005. Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum. Microbiology-Sgm, 151(5), p 1359-1368.
E. Radmacher, et al., “Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum”, Microbiology-Sgm, vol. 151, 2005, pp. 1359-1368.
Radmacher, E., Stansen, K.C., Besra, G.S., Alderwick, L.J., Maughan, W.N., Hollweg, G., Sahm, H., Wendisch, V.F., Eggeling, L.: Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum. Microbiology-Sgm. 151, 1359-1368 (2005).
Radmacher, E., Stansen, K. C., Besra, G. S., Alderwick, L. J., Maughan, W. N., Hollweg, G., Sahm, H., Wendisch, Volker F., and Eggeling, L. “Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum”. Microbiology-Sgm 151.5 (2005): 1359-1368.

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