Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases

Catherine Paradis-Bleau, Monica Markovski, Tsuyoshi Uehara, Tania J. Lupoli, Suzanne Walker, Daniel E. Kahne, Thomas G. Bernhardt

Research output: Contribution to journalArticle

Abstract

Most bacteria surround themselves with a peptidoglycan (PG) exoskeleton synthesized by polysaccharide polymerases called penicillin-binding proteins (PBPs). Because they are the targets of penicillin and related antibiotics, the structure and biochemical functions of the PBPs have been extensively studied. Despite this, we still know surprisingly little about how these enzymes build the PG layer in vivo. Here, we identify the Escherichia coli outer-membrane lipoproteins LpoA and LpoB as essential PBP cofactors. We show that LpoA and LpoB form specific trans-envelope complexes with their cognate PBP and are critical for PBP function in vivo. We further show that LpoB promotes PG synthesis by its partner PBP in vitro and that it likely does so by stimulating glycan chain polymerization. Overall, our results indicate that PBP accessory proteins play a central role in PG biogenesis, and like the PBPs they work with, these factors are attractive targets for antibiotic development.

Original languageEnglish (US)
Pages (from-to)1110-1120
Number of pages11
JournalCell
Volume143
Issue number7
DOIs
StatePublished - Dec 23 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Paradis-Bleau, C., Markovski, M., Uehara, T., Lupoli, T. J., Walker, S., Kahne, D. E., & Bernhardt, T. G. (2010). Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases. Cell, 143(7), 1110-1120. https://doi.org/10.1016/j.cell.2010.11.037