Integral outer membrane proteins (OMPs) are crucial for the maintenance of the proteobacterial envelope permeability barrier to some antibiotics and detergents. In Enterobacteria, envelope stress caused by unfolded OM proteins (OMPs) activates the sigmaE (σE) transcriptional response. σE upregulates OMP-biogenesis factors, including the b-barrel assembly machinery (BAM) that catalyzes OMP folding. Here we report that DolP (formerly YraP), a σE-upregulated and poorly understood OM lipoprotein, is crucial for fitness in cells that undergo envelope stress. We demonstrate that DolP interacts with the BAM complex by associating to OM-assembled BamA. We provide evidence that DolP is important for proper folding of BamA that overaccumulates in the OM, thus supporting OMP biogenesis and OM integrity. Notably, mid-cell recruitment of DolP had been linked to regulation of septal peptidoglycan remodelling by an unknown mechanism. We now reveal that, during envelope stress, DolP loses its association with the mid-cell, thereby suggesting a mechanistic link between envelope stress caused by impaired OMP biogenesis and the regulation of a late step of cell division.

In Gram-negative bacteria, coordinated remodelling of the outer membrane (OM) and the peptidoglycan is crucial for envelope integrity. Envelope stress caused by unfolded OM proteins (OMPs) activates sigmaE(σE) in Enterobacteria. Whereas σE upregulates biogenesis factors, including the β-barrel assembly machinery (BAM) that catalyzes OMP-folding, elevated σE activity can be detrimental for OM integrity. We report that DolP (YraP), a σE-upregulated OM lipoprotein needed for envelope integrity, is a novel interactor of BAM and that BamA is a critical determinant of the BAM-DolP complex. Mid-cell recruitment of DolP had been reported to promote septal peptidoglycan remodelling during cell division, but the role of DolP during envelope stress was unknown. Using a synthetic-defect CRISPRi screen, we found that dolP is critical in cells with elevated or constitutive σE activation. Differently from other σE-upregulated proteins, DolP is not directly implicated in OMP assembly. Envelope stress or OM-overaccumulating BamA, however, interferes with DolP septal recruitment. Taken together, our results uncover DolP as a fitness factor during σE activation, and support a model where differential septal recruitment of DolP contributes to link envelope stress to a late step of cell division.

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