Journal
NATURE
Volume 606, Issue 7916, Pages 953-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-022-04834-7
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Funding
- European Union [721484]
- Medical Research Council (MRC) [MR/NOO2679/1]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/W005557/1]
- European Research Council [742555]
- Wellcome Trust collaborative award [201505/Z/16/Z]
- BBSRC UK [BB/P009948/1]
- BBSRC [BB/P009840/1, BB/S017283/1]
- EMBO Long-Term Fellowship [ALTF 485-2017]
- Micron Advanced Bioimaging Unit (Wellcome Strategic Awards) [091911/B/10/Z, 107457/Z/15/Z]
- BBSRC [BB/W005557/1, BB/P009948/1] Funding Source: UKRI
- European Research Council (ERC) [742555] Funding Source: European Research Council (ERC)
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The spatiotemporal organization of outer membrane proteins (OMPs) in Gram-negative bacteria is modulated by the presence of mature peptidoglycan, which inhibits OMP foldase activity and promotes preferential insertion of OMPs at division sites. This coordination between OMP biogenesis and peptidoglycan maturation represents a potential vulnerability that could be targeted in future antibiotic design.
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 beta-barrel assembly machine(6,7) (BAM). Growing Escherichia coli cells segregate old OMP stowards 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.
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