Peptidoglycan Synthesis in Mycobacterium Tuberculosis Is Organized Into Networks with Varying Drug Susceptibility
Peptidoglycan synthesis in Mycobacterium tuberculosis is organized into networks with varying drug susceptibility Karen J. Kiesera, Catherine Baranowskia, Michael C. Chaob, Jarukit E. Longc, Christopher M. Sassettic,d, Matthew K. Waldorb,d,e, James C. Sacchettinif, Thomas R. Ioergerg, and Eric J. Rubina,e,1 aDepartment of Immunology and Infectious Disease, Harvard T. H. Chan School of Public Health, Boston, MA 02115; bDivision of Infectious Diseases, Brigham & Women’s Hospital, Boston, MA 02115; cDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester MA 01655; dHoward Hughes Medical Institute, Chevy Chase, MD 20815; eDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; fDepartment of Biochemistry and Biophysics and Department of Chemistry, Texas A&M University, College Station, TX 77843; and gDepartment of Computer Science, Texas A&M University, College Station, TX 77843 Edited by Carolyn R. Bertozzi, University of California, Berkeley, CA, and approved September 8, 2015 (received for review July 17, 2015) Peptidoglycan (PG), a complex polymer composed of saccharide proper cell-wall synthesis. One method of coordination is the use chains cross-linked by short peptides, is a critical component of the of large protein complexes, the elongation complex and divisome, bacterial cell wall. PG synthesis has been extensively studied in which mediate cell-wall biogenesis during cell elongation or di- model organisms but remains poorly understood in mycobacteria, vision, respectively (2). The essential activity of these enzymes a genus that includes the important human pathogen Mycobacte- makes them prime drug targets; indeed, PBPs and Ldts are inhibited rium tuberculosis (Mtb). The principle PG synthetic enzymes have by carbapenems and penicillin (6, 7), which remains one of the most similar and, at times, overlapping functions.
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