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Cell wall targets in methicillin-resistant staphylococci
Harald Labischinski1, Lars Johannsen
1Pharma Research Center, Wuppertal, Germany
Abstract:
Multiresistant staphylococci pose an alarmingly growing problem, especially in serious hospital infections. The recent emergence of strains with reduced susceptibility against vancomycin, the last remaining drug effective against methicillin (multi) resistant Staphylococcus aureus, highlights the urgent need for new antimicrobial agents and new therapeutic regimen. Previously, new drugs were discovered exclusively in bacterial whole cell growth assays. Today's more rational approach depends on the identification of suitable target genes and proteins. These should be bacteria-specific and essential for growth either in vitro or in vivo. Targets within cell wall synthesis and remodeling pathways might be particularly attractive because the bacterial cell wall is a unique structure occurring only in prokaryots; many of the antibiotics in use today have confirmed its 'drugability'. However, several potential targets within this field have not yet been exploited successfully for anti-staphylococcal therapy and some were discovered only recently. After a short summary of known potential targets a set of genes involved in the pentaglycine interpeptide bridge formation of the staphylococcal cell wall will be introduced as interesting targets to combat multiresistant staphylococcal infections. Copyright 1999 Harcourt Publishers LtdCopyright DUMMY.
Insights
Multiresistant staphylococci infections are a growing concern. New therapeutic targets, like those in staphylococcal cell wall synthesis, are urgently needed to combat resistant bacterial strains.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Multiresistant staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA), present a significant threat in hospital settings.
- Vancomycin resistance in staphylococci necessitates the development of novel antimicrobial agents and therapeutic strategies.
- Traditional drug discovery methods are being replaced by rational approaches targeting essential bacterial-specific genes and proteins.
Purpose of the Study:
- To identify and evaluate novel therapeutic targets for combating multiresistant staphylococcal infections.
- To explore the potential of bacterial cell wall synthesis and remodeling pathways as targets for new antimicrobial drugs.
- To introduce specific genes involved in pentaglycine interpeptide bridge formation as promising targets.
Main Methods:
- Review of existing literature on potential antimicrobial targets in staphylococci.
- Identification and characterization of genes crucial for staphylococcal cell wall biosynthesis, specifically the pentaglycine interpeptide bridge.
- Analysis of the 'drugability' of bacterial cell wall components.
Main Results:
- The bacterial cell wall, a prokaryote-specific structure, offers a rich source of potential antimicrobial drug targets.
- Several targets within cell wall synthesis pathways remain underexploited for anti-staphylococcal therapy.
- Genes involved in the pentaglycine interpeptide bridge formation have been identified as promising targets.
Conclusions:
- Targeting the staphylococcal cell wall synthesis pathway, particularly the pentaglycine interpeptide bridge, presents a viable strategy against multiresistant staphylococci.
- The rational drug design approach focusing on essential bacterial-specific targets is crucial for overcoming antimicrobial resistance.
- Further research into these novel targets could lead to the development of effective treatments for challenging staphylococcal infections.