Here we investigated the key player in the cell envelope organization; a small, alpha-helical Braun’s lipoprotein protein (LPP). Lpp provides the only covalent connection between the outer membrane (OM) and the peptidoglycan (PG). The N-terminus is attached to the OM while the C-terminus is attached to the PG, catalysed by enzymes with L,D-transpeptidase activity; LdtA, LdtB, and LdtC (Yakushi et al., 1997). Recent work has shown that the width of the periplasm is controlled largely by Lpp. Lengthening of Lpp, that allowed the expansion of the periplasm leads to a longer flagella rod and more efficient swimming behavior in Salmonella typhimurium (Cohen et al., 2017). In another similar study, increasing the periplasmic width revealed a signaling function of envelop damage controlled by Regulator of capsule synthesis F (RcsF) in Escherichia coli (Asmar et al., 2017). Bearing in mind the many other important cellular functions taking place in the periplasm: cell division regulation, osmoregulation, peptidoglycan synthesis, multidrug efflux systems, and many others, we sought to use a genetic screening approach to identify other periplasmic processes that are dependent on the periplasmic architecture. Here we report the effect of a widened periplasm on peptidoglycan assembly. The activation of the major penicillin binding proteins (PBP1A and PBP1B) by their cognate lipoproteins (LpoA and LpoB) is compromised which leads to synthetic lethal phenotype when either of the redundant pathway is removed. These genetic screen results are further studied to better understand the coordination between the OM biogenesis and peptidoglycan biogenesis in bacterial cell elongation.