Year: 2022
Type: article
Abstract: 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 environments1–5. The function of the outer membrane is dependent on outer membrane proteins (OMPs), which are inserted into the membrane by the β-barrel assembly machine6,7 (BAM). Growing Escherichia coli cells segregate old OMPs towards the poles by a process known as binary partitioning, the basis of which is unknown8. 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 septa9, 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.
Source: Nature
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,390
Awards: MICA: Mechanistic understanding of cell wall biosynthesis to combat antimicrobial resistance, Bacterial Cell Envelope Biogenesis, Spatiotemporal organisation of bacterial outer membrane proteins, Crossing the periplasmic void, elucidating the mechanisms of phospholipid transport in Gram-negative bacteria, G1983671959, Micron Oxford: super-resolution imaging of cellular dynamics., Protein import through the E. coli cell envelope, Unravelling the Bam complex, G434337789, Protein Antibiotics: Discovery, mode of action and development, G6868616705, Advanced Microscopy for Chromosome and RNA Dynamics., An integrated mulTidisciplinary appRoach towards a new generAtIon of aNtibiotics: Targeting function and cross-talk of bacterial Envelope proTein machineries
OpenAlex ID: W4282978620