Abstract
In enterobacteria, the Rcs system (Regulator of capsule synthesis) monitors envelope integrity and induces a stress response when damages occur in the outer membrane or in the peptidoglycan layer. Built around a two-component system, Rcs controls gene expression via a cascade of phosphoryl transfer reactions. Being particularly complex, Rcs also involves the outer membrane lipoprotein RcsF and the inner membrane essential protein IgaA (Intracellular growth attenuator). RcsF and IgaA, which are located upstream of the phosphorelay, are required for normal Rcs functioning. Here, we establish the stress-dependent formation of a complex between RcsF and the periplasmic domain of IgaA as the molecular signal triggering Rcs. Moreover, molecular dissection of IgaA reveals that its negative regulatory role on Rcs is mostly carried by its first N-terminal cytoplasmic domain. Altogether, our results support a model in which IgaA regulates Rcs activation by playing a direct role in the transfer of signals from the cell envelope to the cytoplasm. This remarkable feature further distinguishes Rcs from other envelope stress response systems.
Highlights
IntroductionGram-negative bacteria are surrounded by the cell envelope, a multi-layered structure composed of an outer membrane (OM) and an inner membrane (IM)
A thorough understanding of the mechanisms that allow bacteria to thrive in various environments is crucial to the development of new antibiotics, an urgent endeavor to combat antimicrobial resistance
We provide evidence that IgaA works in concert with RcsF, a lipoprotein that is posted as a sentinel in the outermost envelope layer, to detect envelope stress: under stress conditions, RcsF forms a complex with the C-terminal, periplasmic domain of IgaA
Summary
Gram-negative bacteria are surrounded by the cell envelope, a multi-layered structure composed of an outer membrane (OM) and an inner membrane (IM). These two membranes delimit the periplasm, a viscous and oxidizing compartment enclosing the cell wall, a thin peptidoglycan (PG) layer. Rcs modulates the expression of dozens of genes, including those involved in the biosynthesis of colanic acid, an exopolysaccharide that accumulates on the cell surface to form a protective capsule [5,6]. In addition to its role in capsule formation, Rcs is required for normal biofilm development and regulates virulence-associated structures [5,7]
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