β-Barrel outer membrane proteins suppress mTORC2 activation and induce autophagic responses

2018 ◽  
Vol 11 (558) ◽  
pp. eaat7493 ◽  
Author(s):  
Anu Chaudhary ◽  
Cassandra Kamischke ◽  
Mara Leite ◽  
Melissa A. Altura ◽  
Loren Kinman ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Epithelial Cells ◽  
Outer Membrane ◽  
Cellular Response ◽  
Tertiary Structure ◽  
Inflammatory Responses ◽  
Outer Membrane Proteins ◽  
Cell Surface Receptor ◽  
Mouse Bone Marrow ◽  
Endosomal Acidification

The outer membranes of Gram-negative bacteria and mitochondria contain proteins with a distinct β-barrel tertiary structure that could function as a molecular pattern recognized by the innate immune system. Here, we report that purified outer membrane proteins (OMPs) from different bacterial and mitochondrial sources triggered the induction of autophagy-related endosomal acidification, LC3B lipidation, and p62 degradation. Furthermore, OMPs reduced the phosphorylation and therefore activation of the multiprotein complex mTORC2 and its substrate Akt in macrophages and epithelial cells. The cell surface receptor SlamF8 and the DNA-protein kinase subunit XRCC6 were required for these OMP-specific responses in macrophages and epithelial cells, respectively. The addition of OMPs to mouse bone marrow–derived macrophages infected withSalmonellaTyphimurium facilitated bacterial clearance. These data identify a specific cellular response mediated by bacterial and mitochondrial OMPs that can alter inflammatory responses and influence the killing of pathogens.

scholarly journals Mosaic Evolution of Beta Barrel Porin Encoding Genes in Escherichia coli

2021 ◽  
Author(s):  
Xiongbin Chen ◽  
Xuxia Cai ◽  
Zewei Chen ◽  
Jinjin Wu ◽  
Gaofeng Hao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Membrane Proteins ◽  
Outer Membrane ◽  
Tertiary Structure ◽  
Outer Membrane Proteins ◽  
Common Mechanism ◽  
General Strategy ◽  
Variable Regions ◽  
Mosaic Evolution ◽  
Encoding Genes

AbstractBacterial porins serve as the interface interacting with extracellular environment, and are often found under positive selection to fit in different environmental stresses. Local recombination has been identified in a handful of porin genes to facilitate the rapid adaptation of bacterial cells. It remains unknown whether it is a common evolutionary mechanism in gram-negative bacteria for all or a majority of the outer membrane proteins. In this research, we investigated the β-barrel porin encoding genes in Escherichia coli that were reported under positive Darwinia selection. Besides fhuA that was found with ingenic local recombination predominantly previously, we identified four other genes, i.e., lamB, ompA, ompC and ompF, all showing the similar mosaic evolution patterns as in fhuA. Comparative analysis of the protein sequences disclosed a list of highly variable regions in each protein family, which are mostly located in the convex of extracellular loops and coinciding with the binding sites of various bacteriophages. For each of the porin family, mosaic recombination leads to various combinations of the HVRs with different sequence patterns, generating diverse protein groups. Structure modeling further indicated the conserved global topology for various groups of each porin family, but the extracellular surface varies a lot that is formed by individual or combinatorial HVRs. The conservation of global tertiary structure ensures the channel activity while the wide diversity of HVRs may assist bacteria avoiding the invasion of phages, antibiotics or immune surveillance factors. In summary, the study identified multiple bacterial porin genes with mosaic evolution, a likely general strategy, by which outer membrane proteins could facilitate the host bacteria to both maintain normal life processes and evade the attack of unflavored environmental factors rapidly.ImportanceMicroevolution studies can disclose more elaborate evolutionary mechanisms of genes, appearing especially important for genes with multifaceted function such as those encoding outer membrane proteins. However, in most cases, the gene is considered as a whole unit and the evolutionary patterns are disclosed. In this research, we reported that multiple bacterial porin proteins follow mosaic evolution, with local ingenic recombination combined with spontaneous mutations based positive Darwinia selection, and conservation for most of the other regions. It could represent a common mechanism for bacterial outer membrane proteins. The study also provides insights on development of new anti-bacterial agent or vaccines.

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