Abstract
ABSTRACTMembers of the genus Mycobacterium are the most prevalent cause of infectious diseases. Mycobacteria have a complex cell envelope containing a peptidoglycan layer and an additional arabinogalactan polymer to which a mycolic acid bilayer is linked; this complex, multilayered cell wall composition (mAGP) is conserved among all CMN group bacteria. The arabinogalactan and mycolic acid synthesis pathways constitute effective drug targets for tuberculosis treatment. Ethambutol (EMB), a classical antituberculosis drug, inhibits the synthesis of the arabinose polymer. Although EMB acts bacteriostatically, its underlying molecular mechanism remains unclear. Here, we used Corynebacterium glutamicum and Mycobacterium phlei as model organisms to study the effects of EMB at the single-cell level. Our results demonstrate that EMB specifically blocks apical cell wall synthesis, but not cell division, explaining the bacteriostatic effect of EMB. Furthermore, the data suggest that members of the family Corynebacterineae have two dedicated machineries for cell elongation (elongasome) and cytokinesis (divisome).
Highlights
Members of the genus Mycobacterium are the most prevalent cause of infectious diseases
EMB is a cell wallacting antibiotic that targets enzymes that are part of the actinobacterial AG synthesis machinery [19]
EMB is most effective against mycobacteria, which require their mAGP layer for viability
Summary
Members of the genus Mycobacterium are the most prevalent cause of infectious diseases. We analyzed the molecular effects of ethambutol, a first-line antibiotic against infections caused by members of the genus Mycobacterium. We find that this drug selectively blocks apical cell growth but still allows for effective cytokinesis. The synthesis pathway of this mycolyl-AG-PG (mAGP) complex has been extensively studied over the past years, and many reactions and their corresponding enzymes have been elucidated [4] Mycobacterium species share this complex cell wall composition with other members of the order Actinomycetales, such as Corynebacterium and Nocardia species. C. glutamicum, in particular, has emerged as an excellent tool for studying apical growth in bacteria [12]
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