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Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
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Targeting Lipoprotein Biogenesis: Considerations towards Antimicrobials.

Toufic El Arnaout1, Tewfik Soulimane2

  • 1Kappa Crystals Ltd, Dublin, Ireland; School of Food Science and Environmental Health, Technological University (TU) Dublin City Campus, TU, Dublin, Dublin, Ireland.

Trends in Biochemical Sciences
|May 1, 2019
PubMed
Summary
This summary is machine-generated.

Developing new antibiotics is challenging, but targeting the lipoprotein maturation pathway shows promise. The enzyme LspA is identified as a key target for novel antibiotics against drug-resistant bacteria.

Keywords:
antibiotic resistancedrug designlipid transferaselipoproteinssignal peptidase

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Area of Science:

  • Microbiology
  • Biochemistry
  • Pharmacology

Background:

  • No new antibiotic classes have been approved in decades, hindering the fight against antimicrobial resistance.
  • Drug discovery efforts have stalled due to significant obstacles.
  • Lipoprotein maturation pathways are critical for bacterial virulence and represent a promising target for novel antibiotics.

Purpose of the Study:

  • To establish considerations and priority-setting for key lipoprotein processing enzymes (Lgt, LspA, and Lnt).
  • To support the rational design of selective drugs targeting bacterial lipoprotein maturation.
  • To identify optimal targets for developing new antibiotics against resistant bacteria.

Main Methods:

  • Review of microbiology, biochemistry, structural biology, chemical design, and pharmacology data.
  • Analysis of the roles of Lgt, LspA, and Lnt in lipoprotein processing.
  • Evaluation of potential drug candidates' impact on bacterial species.

Main Results:

  • The lipoprotein maturation pathway is a viable strategy for novel antibiotic development.
  • LspA emerges as a highly promising target due to its critical role and potential for selective drug design.
  • While not universally effective, drug candidates targeting this pathway show potential against resistant strains.

Conclusions:

  • Targeting bacterial lipoprotein processing enzymes offers a new avenue for antibiotic discovery.
  • LspA is a prioritized target for developing next-generation antibiotics effective against multidrug-resistant pathogens.
  • Further research into LspA inhibitors could lead to urgently needed treatments for bacterial infections.