Will the "secret weapon" to curb E. coli toxicity be revealed, and will new antibiotics be far away?

E. coli is a parasitic bacteria in the intestines of humans and animals.
, E. coli has two distinct membranes: the endometrium and the outer membrane.
the inner membrane is a double molecular layer of phospholipids, while the outer membrane is not symmetrical, a single layer of phospholipids form the inner surface, lipid polysaccharides (LPS) lined on the outer surface.
LPS protects E. coli from antibiotics in the mammalian host's intestines.
the ratio of phospholipids to LPS is very important for membrane function, too much LPS is harmful to the inner membrane, too little will damage the outer membrane.
has long been an unsolt mystery in the scientific community about whether the LPS itself or its prescients are responsible for regulating the feedback signals of LPS biosynthetics. Now, the question has been answered.
On August 12th researchers from Genenteco published their findings in the journal Nature: The endometrial protein PbgA is a struggling LPS signal transduter that reduces E. coli toxicity by reducing LPS levels and outer membrane integrity.
, the researchers first demonstrated the importance of PbgA for the integrity of the outer membrane.
they found that the urinary pathogenic E. coli ppgA deficiency strain contained inhibitory mutations, while E. coli's sensitivity to serum and antibiotic lycopen was restored after the re-introduction of ppgA on the primer, indicating that ppgA was essential.
PbgA is critical to the integrity of the outer membrane It is important to note that, contrary to previous claims that PbgA acts as a heart phospholipid transporter protein, this study proves that PbgA has nothing to do with any known transport protein.
, the researchers analyzed the PpgA structure of 1.9 ngströms using a technique called X-ray crystallization.
they found that PbgA belonged to a family of enzymes, and that the structure of the full-length PbgA was most similar to that of EpteA, a protein that adds phospholipid-derived molecular modifications to the lipid A domain of LPS 17.
by modifying these phosphoric acid groups, EptA provides cells with resistance to antibiotics (polycrystylin) that bind to lipid A.
PbgA structural feature researchers also found that PbgA binds to lipid A parts through the connector domain, while the amino acid sequence used is not reported in any other LPS binding protein, and mutations in the LPS binding sequence disrupt PpgA function.
in the last set of experiments, the researchers demonstrated that synthetic peptides based on this sequence can bind to LPS and inhibit the growth of a variety of Glollath-negative bacteria, including polysycoccid resistant strains.
design, they improved the antibiotic spectrum and effectiveity of the peptide.
PpgA's peritial lipid A binding sequence concluded, the researchers explained how LPS controls its own synthesis: PpgA on the endometrium regulates the activity of the antimicrobial enzyme LpxC, a protein that guides the enzyme FtsH degradation of LpxC.
Therefore, when the LPS level is low, PbgA inhibits the interaction between LapB and FtsH in the endometrium, stabilizing the LpxC and promoting LPS biosynthesis;
PpgA's ability to detect persecondational LPS levels to regulate LpxC stability concludes that this study expands our understanding of PbgA by providing a high-resolution structure of proteins that bind to LPS, while proving that PpgA is an LPS signal conductor.
, the study provides new insights into the development of antibiotics, in addition to clarifying the significant lipid balance in bacterial membranes.
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