Regulated Control of the Assembly and Diversity of LPS by Noncoding sRNAs

Figure 2

A flow chart depicting various steps regulated by noncoding sRNAs during the biosynthesis of LPS or its regulated nonstoichiometric modifications. The LPS biosynthesis begins with the GlmS-mediated synthesis of GlcN6P. GlcN6P serves as a precursor for UDP-GlcNAc, which is a metabolic intermediate for the LPS synthesis. UDP-GlcNAc is acylated by LpxA using R-3-hydroxymyristate, followed by deacylation by LpxC. The expression of the glmS mRNA is regulated by GlmZ/Y sRNAs at the posttranscriptional level, while the amount of LpxC is regulated by FtsH/LapB-mediated turnover. The balanced synthesis of LPS and phospholipids requires SlrA-dependent translational repression of Lpp to feed more fatty acids pools for the phospholipid synthesis. Kdo₂-lipid A modifications are regulated by transcriptional induction of the BasS/R two-component system and RpoE-dependent induction of the eptB gene. PhoP/Q activation can amplify induction of the transcription of BasS/R-regulated eptA, arnT, and pmrD genes. The PhoP synthesis is negatively regulated by MicA and GcvB sRNAs at the translational level. The eptB subjected to translational repression by PhoP/Q-regulated MgrR. The LPS core biosynthesis could be further fine-tuned by regulating sugar uptake and the amount of UDP-Gal and UDP-Glc precursors, requiring SgrS and Spot42 sRNAs. The RpoE-dependent induction of RybB leads to the synthesis of LPS glycoforms with a third Kdo and truncation of the outer core due to translational repression of WaaR by RybB. After the completion of LPS synthesis and its flipping across the IM, lipid A can be modified by LpxT, whose activity is repressed at the posttranslational level by PmrR. After the incorporation of LPS in the outer membrane, lipid A may be further acylated by posttranslational activation of PagP or deacylated by LpxR. The LpxR synthesis is inhibited by MicF at its translational level by base-paring with the lpxR mRNA. Note that LpxR is absent in E. coli K-12 but is presented in several pathogenic E. coli strains and Salmonella. Other lipid A modifications not observed in E. coli K-12 are not shown.