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katherine-medina

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
  • periplasmic
    • katherine-medina
      katherine-medina on 05 Aug 23
       
      The space in between the inner and outer membranes of gram-negative bacteria
  • 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
      katherine-medina on 05 Aug 23
       
      I wonder what other peptides do so as well?
  • ...7 more annotations...
  • We hypothesized that thanatin mainly acts as a competitive inhibitor of the protein-protein interactions mediating the Lpt bridge assembly
  • Thanatin, however, is not a suitable drug candidate for further development due to poor drug-like properties and rapid emergence of resistance
    • katherine-medina
      katherine-medina on 05 Aug 23
       
      Why/How does thanatin have poor drug-like properties?
  • β-jellyroll
    • katherine-medina
      katherine-medina on 05 Aug 23
       
      structure found in proteins
  • Here, we introduce thanatin-derived synthetic macrocyclic peptides found after a substantial medicinal chemistry effort.
    • katherine-medina
      katherine-medina on 05 Aug 23
       
      Essentially they synthetically created it
  • 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
      katherine-medina on 05 Aug 23
       
      That is kinda scary to think about
  • 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.
  • 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
      katherine-medina on 05 Aug 23
       
      It is interesting to look around that these other methods that can fight off bacteria.
  • katherine-medina on 05 Aug 23
     
    An article showing a new class of antibiotics known as a peptidomimetic antibiotic.
katherine-medina

Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechi... - 0 views

www.microbiologyresearch.org/...jmm.0.001060

pathogen polyphenols green-tea HSR-2023 gram-negative-bacteria

shared by katherine-medina on 21 Jun 23 - No Cached
  • epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa
    • katherine-medina
      katherine-medina on 21 Jun 23
       
      Epigallocatechin (EGCG) is a type of catechin or a natural phenol antioxidant. It is commonly found in tea leaves, plums, apple skin, and onions. Sidenote this bacteria is found in green tea
  • However, with resistance increasing against many classes of antibiotic, clinicians often use multiple combinations to treat critically ill patients
  • relatively low toxicity of EGCG to human keratinocytes and G. mellonella larvae.
  • ...12 more annotations...
  • . EGCG was able to restore the activity of aztreonam against MDR P. aeruginosa . The data presented support further evaluation of the aztreonam–EGCG combination and highlight its potential for use in clinical medici
  • Polyphenols
    • katherine-medina
      katherine-medina on 21 Jun 23
       
      These are bioactive compounds that are found in fruits and leaves of plants. The main focus of this paper is a type of polyphenol.
  • with EGCG in checkerboard assays, susceptibility increased in P. aeruginosa (n=16, 100%), with the combination proving synergistic in all strains tested
    • katherine-medina
      katherine-medina on 21 Jun 23
       
      Wow. for how much it increased the susceptibility.
  • Another option to restore the activity of aztreonam against bacterial strains with multiple resistance mechanisms would be to use polyphenols
  • he results demonstrate that synergy between aztreonam and EGCG exists [fractional inhibitory concentration indices (FICIs) 0.02-0.5], with the combination affording significantly (P=<0.05) enhanced bacterial killing, with a >3 log10 reduction in colony-forming units ml−1 at 24 h
  • To access synergy between aztreonam and EGCG, checkerboard assays were performed
  • Chemicals, media, bacterial isolates and animals
    • katherine-medina
      katherine-medina on 21 Jun 23
       
      Really important to look back at these methods because even though it may not be feasible for me to do an experiment like this one, it still has valuable information for me to look at.
  • Synergy was also found between EGCG and the third-generation cephalosporin, cefotaxime
  • with scores of 64 and 56 out of a maximum of 64 for strains PA2 and PA6, respectively.
  • the increased activity may also be due to the inhibition of the non-mevalonate pathway, resulting in increased susceptibility to aztreonam.
  • Overall, the G. mellonella assays demonstrated that the aztreonam–EGCG combination was superior to monotherapy with either agent against every isolate tested, with significantly lower larval mortality rates
  • In conclusion, the results from this study demonstrate that synergy exists between aztreonam and EGCG against MDR clinical strains of P. aeruginosa in vitro and in vivo. EGCG is also able to restore the antibacterial activity of aztreonam to concentrations below the EUCAST susceptibility breakpoint for P. aeruginosa , potentially expanding and extending its useful therapeutic lifespan. Further work should be undertaken to determine if this combination has the potential to treat clinical infections caused by MDR P. aeruginosa .
    • katherine-medina
      katherine-medina on 21 Jun 23
       
      My final thought for this article is as follows: 1. This brings up a very interesting topic for me to dig into (polyphenols & antibiotics)
  • katherine-medina on 21 Jun 23
     
    A gateway article for me to further my search into the scientific realm involving polyphenols that aid antibiotics.
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