TY - JOUR
T1 - Peptidoglycan maturation controls outer membrane protein assembly
AU - Mamou, Gideon
AU - Corona, Federico
AU - Cohen-Khait, Ruth
AU - Housden, Nicholas G
AU - Yeung, Vivian
AU - Sun, Dawei
AU - Sridhar, Pooja
AU - Pazos, Manuel
AU - Knowles, Timothy J
AU - Kleanthous, Colin
AU - Vollmer, Waldemar
PY - 2022/6/15
Y1 - 2022/6/15
N2 - Linkages between the outer membrane of Gram-negative bacteria and the peptidoglycan layer are crucial for the maintenance of cellular integrity and enable survival in challenging environments
1-5. The function of the outer membrane is dependent on outer membrane proteins (OMPs), which are inserted into the membrane by the β-barrel assembly machine
6,7 (BAM). Growing Escherichia coli cells segregate old OMPs towards the poles by a process known as binary partitioning, the basis of which is unknown
8. Here we demonstrate that peptidoglycan underpins the spatiotemporal organization of OMPs. Mature, tetrapeptide-rich peptidoglycan binds to BAM components and suppresses OMP foldase activity. Nascent peptidoglycan, which is enriched in pentapeptides and concentrated at septa
9, associates with BAM poorly and has little effect on its activity, leading to preferential insertion of OMPs at division sites. The synchronization of OMP biogenesis with cell wall growth results in the binary partitioning of OMPs as cells divide. Our study reveals that Gram-negative bacteria coordinate the assembly of two major cell envelope layers by rendering OMP biogenesis responsive to peptidoglycan maturation, a potential vulnerability that could be exploited in future antibiotic design.
AB - Linkages between the outer membrane of Gram-negative bacteria and the peptidoglycan layer are crucial for the maintenance of cellular integrity and enable survival in challenging environments
1-5. The function of the outer membrane is dependent on outer membrane proteins (OMPs), which are inserted into the membrane by the β-barrel assembly machine
6,7 (BAM). Growing Escherichia coli cells segregate old OMPs towards the poles by a process known as binary partitioning, the basis of which is unknown
8. Here we demonstrate that peptidoglycan underpins the spatiotemporal organization of OMPs. Mature, tetrapeptide-rich peptidoglycan binds to BAM components and suppresses OMP foldase activity. Nascent peptidoglycan, which is enriched in pentapeptides and concentrated at septa
9, associates with BAM poorly and has little effect on its activity, leading to preferential insertion of OMPs at division sites. The synchronization of OMP biogenesis with cell wall growth results in the binary partitioning of OMPs as cells divide. Our study reveals that Gram-negative bacteria coordinate the assembly of two major cell envelope layers by rendering OMP biogenesis responsive to peptidoglycan maturation, a potential vulnerability that could be exploited in future antibiotic design.
KW - Bacterial Outer Membrane Proteins/chemistry
KW - Cell Membrane/chemistry
KW - Cell Wall/metabolism
KW - Escherichia coli Proteins/chemistry
KW - Escherichia coli/chemistry
KW - Peptidoglycan/biosynthesis
KW - Protein Folding
UR - http://www.scopus.com/inward/record.url?scp=85131919320&partnerID=8YFLogxK
U2 - 10.1038/s41586-022-04834-7
DO - 10.1038/s41586-022-04834-7
M3 - Article
C2 - 35705811
SN - 0028-0836
VL - 606
SP - 953
EP - 959
JO - Nature
JF - Nature
IS - 7916
ER -