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Peptidomimetic antibiotics disrupt the lipopolysaccharide transport bridge of drug-resi... - 0 views

www.science.org/...sciadv.adg3683

bacteria-killing HSR2023 peptide drug-resistant thanatin

shared by katherine-medina on 05 Aug 23 - No Cached

Recently, naturally occurring peptides were proposed to interfere with the function of proteins constituting the lipopolysaccharide
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periplasmic
- katherine-medina on 05 Aug 23
  
  The space in between the inner and outer membranes of gram-negative bacteria
  
  <div class="cArrow"> </div><div class="cContentInner">The space in between the inner and outer membranes of gram-negative bacteria</div>
  
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Thanatin, a 21–amino acid defense peptide isolated from the gut of the hemipteran insect Podisus maculiventris (18), exhibits broad-spectrum antimicrobial activity
- katherine-medina on 05 Aug 23
  
  I wonder what other peptides do so as well?
  
  <div class="cArrow"> </div><div class="cContentInner">I wonder what other peptides do so as well?</div>
  
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We hypothesized that thanatin mainly acts as a competitive inhibitor of the protein-protein interactions mediating the Lpt bridge assembly
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Thanatin, however, is not a suitable drug candidate for further development due to poor drug-like properties and rapid emergence of resistance
- katherine-medina on 05 Aug 23
  
  Why/How does thanatin have poor drug-like properties?
  
  <div class="cArrow"> </div><div class="cContentInner">Why/How does thanatin have poor drug-like properties?</div>
  
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β-jellyroll
- katherine-medina on 05 Aug 23
  
  structure found in proteins
  
  <div class="cArrow"> </div><div class="cContentInner">structure found in proteins</div>
  
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Here, we introduce thanatin-derived synthetic macrocyclic peptides found after a substantial medicinal chemistry effort.
- katherine-medina on 05 Aug 23
  
  Essentially they synthetically created it
  
  <div class="cArrow"> </div><div class="cContentInner">Essentially they synthetically created it</div>
  
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Development of resistance against thanatin was observed after 1 day of passaging in both E. coli and K. pneumoniae and is characterized by a spontaneous FOR of 1.2 × 10−6 for E. coli at 4× MIC
- katherine-medina on 05 Aug 23
  
  That is kinda scary to think about
  
  <div class="cArrow"> </div><div class="cContentInner">That is kinda scary to think about</div>
  
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genome sequencing of a diverse panel of thanatin-resistant strains confirmed on-target modifications on LptA as the main resistance determinant in E. coli and K. pneumoniae.
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The attractive in vitro and in vivo profile of these new antibiotics, coupled with their novel mechanism of action, showing no cross-resistance to standard of care antibiotics, may provide clinicians with additional treatment options to fight AMR, either in combination with SoC or as stand-alone antibiotics.
- katherine-medina on 05 Aug 23
  
  It is interesting to look around that these other methods that can fight off bacteria.
  
  <div class="cArrow"> </div><div class="cContentInner">It is interesting to look around that these other methods that can fight off bacteria.</div>
  
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katherine-medina on 05 Aug 23

An article showing a new class of antibiotics known as a peptidomimetic antibiotic.

<div class="cArrow"> </div><div class="cContentInner">An article showing a new class of antibiotics known as a peptidomimetic antibiotic.</div>

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