Identification of Lpp as the bacterial periplasmic size keeper : size matters for envelope-spanning systems

Across the cell envelope of Gram-negative bacteria, many vital processes operate and are thoroughly studied. Even though considerable insight has been brought into their function and mechanism, how these envelope systems cross-talk or coordinate in space and time remains poorly explored. Moreover, how the dimensions of the envelope structure are maintained and how their variations affect different cellular processes is an intriguing field to investigate. In the first part of my thesis, I studied the lipoprotein Lpp which is anchored in the outer-membrane of the envelope by a lipid moiety covalently attached to its N-terminus. Lpp is the first lipoprotein that was discovered in E. coli. Although hundreds of lipoproteins were discovered since then in Gram-negative and Gram-positive bacteria, no lipoprotein could surpass Lpp’s unique features. Not only is Lpp the numerically most abundant protein in E. coli, but also the only protein that provides a covalent connection between its C-terminus and the peptidoglycan. The function of Lpp remained unclear for decades since its discovery in the late sixties. My work unraveled the key function of Lpp, baptizing it as a major periplasmic size determinant in the bacterial cell envelope. I also demonstrated the physiological importance of this periplasmic size: I showed that it is optimal for the functioning of the stress response system Rcs and that alteration of the periplasmic dimensions dramatically affects the Rcs signaling and likely other envelope-spanning systems. The second part of my thesis is dedicated to a side-project, in which I examined the folding of the Rcs system sensor RcsF. In particular, I wondered about how the formation of native disulfide bonds in RcsF is orchestrated with the targeting of RcsF to the outer-membrane and with its role in sensing the cues that induce the Rcs pathway.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201