Therapeutic compounds targeting Lipid II for antibacterial purposes
Jakob J Malin1,2, Erik de Leeuw3
1University of Cologne, Department I of Internal Medicine, Division of Infectious Diseases, Cologne, Germany.
Abstract:
Resistance against commonly used antibiotics has emerged in all bacterial pathogens. In fact, there is no antibiotic currently in clinical use against which resistance has not been reported. In particular, rapidly increasing urbanization in developing nations are sites of major concern. Additionally, the widespread practice by physicians to prescribe antibiotics in cases of viral infections puts selective pressure on antibiotics that still remain effective and it will only be a matter of time before resistance develops on a large scale. The biosynthesis pathway of the bacterial cell wall is well studied and a validated target for the development of antibacterial agents. Cell wall biosynthesis involves two major processes; 1) the biosynthesis of cell wall teichoic acids and 2) the biosynthesis of peptidoglycan. Key molecules in these pathways, including enzymes and precursor molecules are attractive targets for the development of novel antibacterial agents. In this review, we will focus on the major class of natural antibacterial compounds that target the peptidoglycan precursor molecule Lipid II; namely the glycopeptides, including the novel generation of lipoglycopeptides. We will discuss their mechanism-of-action and clinical applications. Further, we will briefly discuss additional peptides that target Lipid II such as the lantibiotic nisin and defensins. We will highlight recent developments and future perspectives.
Insights
Antibiotic resistance is a growing global threat. This review explores glycopeptides and lipoglycopeptides that target bacterial cell wall biosynthesis, offering new hope against resistant pathogens.
Area of Science:
- Microbiology
- Drug Discovery
- Biochemistry
Background:
- Antibiotic resistance is a critical global health challenge, exacerbated by urbanization and inappropriate antibiotic use.
- The bacterial cell wall biosynthesis pathway presents a validated target for novel antibacterial agents.
- Peptidoglycan and teichoic acid biosynthesis are key processes in bacterial cell wall formation.
Purpose of the Study:
- To review natural antibacterial compounds targeting the peptidoglycan precursor Lipid II.
- To discuss glycopeptides, lipoglycopeptides, lantibiotics, and defensins.
- To highlight recent advancements and future directions in targeting Lipid II.
Main Methods:
- Literature review focusing on natural antibacterial compounds.
- Analysis of mechanisms of action and clinical applications of glycopeptides and lipoglycopeptides.
- Discussion of other Lipid II-targeting peptides like nisin and defensins.
Main Results:
- Glycopeptides and lipoglycopeptides are major classes of natural compounds targeting Lipid II.
- These compounds exhibit significant antibacterial activity against resistant strains.
- Nisin and defensins are additional examples of Lipid II-targeting antibacterial peptides.
Conclusions:
- Targeting Lipid II in bacterial cell wall biosynthesis is a promising strategy for developing new antibiotics.
- Glycopeptides and lipoglycopeptides represent a valuable class of therapeutics with potential against resistant bacteria.
- Continued research into Lipid II-targeting agents is crucial for combating antibiotic resistance.
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