Ethambutol-induced alterations in Mycobacterium bovis BCG imaged by atomic force microscopy.
Progress in understanding the structure-function relationships of the mycobacterial cell wall has been hampered by its complex architecture as well as by the lack of sensitive, high-resolution probing techniques. For the first time, we used atomic force microscopy (AFM) to image the surface topography of hydrated Mycobacterium bovis bacillus Calmette Guérin cells and to investigate the influence of the antimycobacterial drug ethambutol on the cell wall architecture. While untreated cells showed a very smooth and homogeneous surface morphology, incubation of cells in the presence of ethambutol caused dramatic changes of the fine surface structure. At 4 micro g mL(-1), the drug created concentric striations at the cell surface and disrupted a approximately 8 nm thick cell wall layer, attributed to the outer electron-opaque layer usually seen by electron microscopy, while at 10 micro g mL(-1) an underlying approximately 12 nm thick layer reflecting the thick electron-transparent layer was also altered. These noninvasive ultrastructural investigations provide novel information on the macromolecular architecture of the mycobacterial envelope as well as into the destructuring effects of ethambutol.
Verbelen
Claire
C
Unité de Chimie des Interfaces, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Dupres
Vincent
V
Menozzi
Franco D
FD
Raze
Dominique
D
Baulard
Alain R
AR
Hols
Pascal
P
Dufrêne
Yves F
YF
D000995:Antitubercular Agents / Q000494:pharmacology; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000648:ultrastructure; D004977:Ethambutol / Q000494:pharmacology*; D018625:Microscopy, Atomic Force; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000648:ultrastructure
D000995:Antitubercular Agents; D004977:Ethambutol