Mechanisms of incorporation for D-amino acid probes that target peptidoglycan biosynthesis

Erkin Kuru, Atanas Radkov, Xin Meng, Alexander Egan, Laura Alvarez, Amanda Dowson, Garrett Booher, Eefjan Breukink, David I. Roper, Felipe Cava, Waldemar Vollmer, Yves Brun, Michael S. VanNieuwenhze

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Bacteria exhibit a myriad of different morphologies, through the synthesis and modification of their essential peptidoglycan (PG) cell wall. Our discovery of a fluorescent D-amino acid (FDAA)-based PG labeling approach provided a powerful method for observing how these morphological changes occur. Given that PG is unique to bacterial cells and a common target for antibiotics, understanding the precise mechanism(s) for incorporation of (F)DAA-based probes is a crucial determinant in understanding the role of PG synthesis in bacterial cell biology and could provide a valuable tool in the development of new antimicrobials to treat drug-resistant antibacterial infections. Here, we systematically investigate the mechanisms of FDAA probe incorporation into PG using two model organisms Escherichia coli (Gram-negative) and Bacillus subtilis (Gram-positive). Our in vitro and in vivo data unequivocally demonstrate that these bacteria incorporate FDAAs using two extracytoplasmic pathways: through activity of their D...
Original languageEnglish
Pages (from-to)2745-2756
Number of pages12
JournalACS Chemical Biology
Volume14
Issue number12
DOIs
Publication statusPublished - 2019

Keywords

  • peptides and proteins
  • bacteria genetics
  • labeling ptobes

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