Related Experiment Video
Updated: Feb 19, 2026
11:56
Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
14.7K
Metabolic Mitigation of Staphylococcus aureus Vancomycin Intermediate-Level Susceptibility
Stewart G Gardner1, Darrell D Marshall2, Robert S Daum3,4,5
1School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Antimicrobial Agents and Chemotherapy
|November 8, 2017
Summary
Vancomycin-intermediate Staphylococcus aureus (VISA) develops resistance through metabolic changes. Targeting amino sugar and purine biosynthesis with vancomycin shows synergistic potential against VISA infections.
Area of Science:
- Microbiology
- Metabolic Engineering
- Antimicrobial Resistance
Background:
- Staphylococcus aureus is a significant human pathogen.
- Increasing antibiotic resistance, including to vancomycin, complicates treatment.
- Vancomycin-intermediate S. aureus (VISA) resistance mechanisms are not fully understood.
Purpose of the Study:
- To identify metabolic adaptations enabling vancomycin resistance in S. aureus.
- To evaluate the therapeutic potential of targeting these metabolic pathways.
Main Methods:
- Comparative metabolomic analysis of vancomycin-sensitive and VISA strains.
- Assessment of synergistic effects of pathway inhibitors combined with vancomycin.
Main Results:
- VISA strains exhibited increased acetogenesis, pentose phosphate pathway flux, and biosynthesis of cell wall precursors and purines.
- Tricarboxylic acid (TCA) cycle activity was decreased in VISA strains.
- Inhibitors of amino sugar and purine biosynthesis demonstrated synergistic killing of VISA strains with vancomycin.
Conclusions:
- Metabolic reprogramming is crucial for adaptive vancomycin resistance in S. aureus.
- Combinatorial therapy targeting metabolic pathways offers a promising strategy to overcome VISA infections.
Related Concept Videos
01:28Antimicrobial Effectiveness
1.1K
The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
1.1K
01:30Development of Antibiotic Resistance
1.6K
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
1.6K
01:27Combined Effects of Drugs: Synergism
7.0K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
7.0K
01:31Defense Against Bacterial Pathogens
3.0K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
3.0K