Identification of new components of the RipC-FtsEX cell separation pathway of < i > Corynebacterineae < /i >

by Hoong Chuin Lim, Joel W. Sher, Frances P. Rodriguez-Rivera, Coralie Fumeaux, Carolyn R. Bertozzi, Thomas G. Bernhardt Several important human pathogens are represented in the Corynebacterineae suborder, includingMycobacterium tuberculosis andCorynebacterium diphtheriae. These bacteria are surrounded by a multilayered cell envelope composed of a cytoplasmic membrane, a peptidoglycan (PG) cell wall, a second polysaccharide layer called the arabinogalactan (AG), and finally an outer membrane-like layer made of mycolic acids. Several anti-tuberculosis drugs target the biogenesis of this complex envelope, but their efficacy is declining due to resistance. New therapies are therefore needed to treat diseases caused by these organisms, and a better understanding of the mechanisms of envelope assembly should aid in their discovery. To this end, we generated the first high-density library of transposon insertion mutants in the model organismC.glutamicum. Transposon-sequencing was then used to define its essential gene set and identify loci that, when inactivated, confer hypersensitivity to ethambutol (EMB), a drug that targets AG biogenesis. Among the EMBs loci were genes encoding RipC and the FtsEX complex, a PG cleaving enzyme required for proper cell division and its predicted regulator, respectively. Inactivation of the conservedsteAB genes (cgp_1603 –1604) was also found to confer EMB hypersensitivity and cell division defects. A combination of quantitative microscopy, muta...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research