RND transporters protect Corynebacterium glutamicum from antibiotics by assembling the outer membrane
Version of Record online: 18 JUN 2014
© 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 3, Issue 4, pages 484–496, August 2014
How to Cite
MicrobiologyOpen 2014; 3(4): 484–496
- Issue online: 14 AUG 2014
- Version of Record online: 18 JUN 2014
- Manuscript Accepted: 9 MAY 2014
- Manuscript Revised: 28 APR 2014
- Manuscript Received: 17 MAR 2014
- National Institutes of Health/National Institute of Allergy and Infectious Diseases. Grant Numbers: AI092486, AI063054
- Cell envelope;
- membrane transport;
- resistance–nodulation–division family
Corynebacterium–Mycobacterium–Nocardia (CMN) group are the causative agents of a broad spectrum of diseases in humans. A distinctive feature of these Gram-positive bacteria is the presence of an outer membrane of unique structure and composition. Recently, resistance–nodulation–division (RND) transporters (nicknamed MmpLs, Mycobacterial membrane protein Large) have emerged as major contributors to the biogenesis of the outer membranes in mycobacteria and as promising drug targets. In this study, we investigated the role of RND transporters in the physiology of Corynebacterium glutamicum and analyzed properties of these proteins. Our results show that in contrast to Gram-negative species, in which RND transporters actively extrude antibiotics from cells, in C. glutamicum and relatives these transporters protect cells from antibiotics by playing essential roles in the biogenesis of the low-permeability barrier of the outer membrane. Conditional C. glutamicum mutants lacking RND proteins and with the controlled expression of either NCgl2769 (CmpL1) or NCgl0228 (CmpL4) are hypersusceptible to multiple antibiotics, have growth deficiencies in minimal medium and accumulate intracellularly trehalose monocorynomycolates, free corynomycolates, and the previously uncharacterized corynomycolate-containing lipid. Our results also suggest that similar to other RND transporters, Corynebacterial membrane proteins Large (CmpLs) functions are dependent on a proton-motive force.