TY - JOUR
T1 - Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases
AU - Paradis-Bleau, Catherine
AU - Markovski, Monica
AU - Uehara, Tsuyoshi
AU - Lupoli, Tania J.
AU - Walker, Suzanne
AU - Kahne, Daniel E.
AU - Bernhardt, Thomas G.
N1 - Funding Information:
The authors would like to thank D. Rudner, M. Waldor, and members of our laboratories for critical reading of the manuscript. We would also like to thank A. Typas, C. Gross, W. Vollmer, and coworkers for communicating their results in advance of publication. Special thanks to K. Suefuji and J.T. Park for generously providing the UDP-M-pep 5 . This work was supported by the Massachusetts Life Science Center (T.G.B.), the Burroughs Wellcome Fund (T.G.B.), and the National Institutes of Health (R01 AI083365-01A1 for T.G.B, GM066174 for D.E.K., and GM076710 for D.E.K and S.W.). T.G.B. holds a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund. C.P.-B. was supported in part by a fellowship from FRSQ.
PY - 2010/12/23
Y1 - 2010/12/23
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2010.11.037
DO - 10.1016/j.cell.2010.11.037
M3 - Article
C2 - 21183074
AN - SCOPUS:78650497005
SN - 0092-8674
VL - 143
SP - 1110
EP - 1120
JO - Cell
JF - Cell
IS - 7
ER -