Abstract
The peptidoglycan (PG) cell wall is an essential component of the cell envelope of most bacteria. Biogenesis of PG involves a lipid-linked disaccharide-pentapeptide intermediate called lipid II, which must be translocated across the cytoplasmic membrane after it is synthesized in the inner leaflet of this bilayer. Accordingly, it has been demonstrated that MurJ, the proposed lipid II flippase in Escherichia coli, is required for PG biogenesis, and thereby viability. In contrast, MurJ is not essential in Bacillus subtilis because this bacterium produces AmJ, an unrelated protein that is functionally redundant with MurJ. In this study, we investigated why MurJ is not essential in the prominent gastric pathogen, Helicobacter pylori. We found that in this bacterium, Wzk, the ABC (ATP-binding cassette) transporter that flips the lipid-linked O- or Lewis- antigen precursors across the inner membrane, is redundant with MurJ for cell viability. Heterologous expression of wzk in E. coli also suppresses the lethality caused by the loss of murJ. Furthermore, we show that this cross-species complementation is abolished when Wzk is inactivated by mutations that target a domain predicted to be required for ATPase activity. Our results suggest that Wzk can flip lipid II, implying that Wzk is the flippase with the most relaxed specificity for lipid-linked saccharides ever identified.
Highlights
The cell envelope of most bacteria contains a cell wall composed of peptidoglycan (PG) [1]
We hypothesized that Wzk might be the protein that is redundant with MurJ in H. pylori because it is an ABC transporter that can flip various undecaprenyl pyrophosphate (Und-PP)-linked oligo- and poly- saccharides across the cytoplasmic membrane [32]
Since lipid II translocation is required for viability, we reasoned that if MurJ and Wzk are redundant in H. pylori, null murJ and wzk alleles will be synthetic lethal
Summary
The cell envelope of most bacteria contains a cell wall composed of peptidoglycan (PG) [1]. Bacteria build the PG matrix around their cytoplasmic membrane by polymerizing a disaccharide-pentapeptide into glycan chains that are crosslinked by peptide bonds [2, 3]. The resulting PG polymer protects cells from osmotic lysis in hypotonic environments, confers cell shape, and serves as an anchor to which envelope structures can be attached. Given these important roles in bacterial physiology, it is not surprising that inhibiting PG biogenesis is lethal under most conditions and that many antibiotics function by inhibiting this process [4].
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