Nature: The secret weapon to curb E. coli toxicity has been revealed, will the new antibiotics go far?

E. coli is a parasitic bacteria in the intestines of humans and animals, whether it causes disease mainly depends on the type of E. coli.
, E. coli has two distinct membranes: the inner and outer membranes.
membrane is a double molecular layer of phospholipids, while the outer membrane is asymmetrmetric, a single layer of phospholipids forms the inner surface, lipid polysaccharide (LPS) lining on the outer surface.
LPS can protect E. coli from antibiotics in the intestines of mammalian hosts.
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 a mystery to the scientific community about regulating feedback signals for LPS biosynthesis, whether it is LPS itself or one of its presy? Now, the question has been answered.
August 12, researchers from gene Tektronum published their findings in the journal Nature: The endometrial protein PpgA is the LPS signal transdulsor that people struggle to find, and its consumption reduces E. coli toxicity by reducing LPS levels and outer membrane integrity.
, the researchers first demonstrated the importance of PpgA for the integrity of the outer membrane.
They found that the pathogenic E. coli pbgA deficiency strain contained inhibitory mutations, and that the sensitivity of E. coli to serum and antibiotic lycopypin was restored after the reintroducing of pbgA on the mass, suggesting that pbgA was essential.
, contrary to previous claims that PbgA acts as a heartpholipid transport protein, this study proves that PbgA is not related to any known transport protein.
, the researchers analyzed 1.9? ngstr? The PpgA structure of ms.
they found that PbgA belongs to an enzyme family, and that the structure of the full-length PpgA is most similar to EptA, a protein that adds phospholipid-derived molecular modifications to the lipid A domain of LPS 17.
by modifying these phosphate groups, EptA provides cells with resistance to antibiotics (poly mucosin) that bind to lipid A. The
researchers also found that PbgA binds to lipid A through a joint domain, and that the amino acid sequence used is not reported in any other LPS binding protein, and that mutations in the LPS binding sequence disrupt PpgA functionality.
the last set of experiments, researchers demonstrated that synthetic peptides based on this sequence can bind to LPS and inhibit the growth of a variety of Erlan-negative bacteria, including polycoscosin-resistant strains.
by a reasonable design, they improved the antibiotic spectrum and effectiveness of the peptide.
, the researchers explained how LPS controls its own synthesis: PbgA on the inner membrane regulates the activity of the antimicrobial enzyme LpxC, a protein that directs the enzyme FtsH to degrade LpxC.
Therefore, when LPS levels are low, PbgA inhibits the interaction between LapB and FtsH in the inner membrane, stabilizing LpxC and promoting LPS biosynthesis;
summary, this study expands our understanding of PbgA by providing a high-resolution structure of proteins that bind to LPS, and proves that PbgA is an LPS signal transd conductor.
to illustrate the significant lipid balance in bacterial membranes, this study provides new insights into the development of antibiotics.
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