Related Experiment Video

Updated: Aug 4, 2026

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
11:56

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection

Published on: October 25, 2013

Gradual alterations in cell wall structure and metabolism in vancomycin-resistant mutants of Staphylococcus aureus

K Sieradzki1, A Tomasz

  • 1The Rockefeller University, New York, New York 10021, USA.

Journal of Bacteriology
|December 22, 1999
PubMed

Insights

Laboratory-induced vancomycin resistance in Staphylococcus aureus led to decreased methicillin resistance and altered cell wall metabolism. This suggests a trade-off between resistance mechanisms and impacts bacterial cell integrity.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health threat.
  • Vancomycin is a critical antibiotic for treating MRSA infections.
  • Emergence of vancomycin resistance in MRSA necessitates understanding resistance mechanisms.

Purpose of the Study:

  • To investigate the relationship between vancomycin resistance and methicillin resistance in Staphylococcus aureus.
  • To characterize the associated changes in cell wall metabolism during the development of vancomycin resistance.

Main Methods:

  • Selection of vancomycin-resistant laboratory step mutants from a highly methicillin-resistant S. aureus strain (COL).
  • Analysis of cell wall metabolism, including peptidoglycan cross-linking and penicillin-binding protein (PBP) production.
  • Assessment of susceptibility to beta-lactam antibiotics.

Main Results:

  • Increasing vancomycin resistance correlated with decreasing methicillin resistance.
  • Observed abnormalities in cell wall metabolism, including reduced peptidoglycan cross-linking.
  • Down-regulation of penicillin-binding protein 2A (PBP2A) and PBP4 production was noted.
  • Mutants exhibited hypersensitivity to beta-lactam antibiotics, with ceftizoxime (a PBP2 inhibitor) being particularly effective.

Conclusions:

  • Vancomycin resistance acquisition in MRSA may involve a trade-off with methicillin resistance.
  • Alterations in cell wall metabolism and PBP expression are associated with vancomycin resistance.
  • Targeting specific PBPs, like PBP2, could be a therapeutic strategy against vancomycin-resistant MRSA.

More Related Videos

A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus08:03

A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus

Published on: March 28, 2017

Atomic Force Microscopy Combined with Infrared Spectroscopy as a Tool to Probe Single Bacterium Chemistry08:51

Atomic Force Microscopy Combined with Infrared Spectroscopy as a Tool to Probe Single Bacterium Chemistry

Published on: September 15, 2020

Related Concept Videos

Bacterial Cell Wall01:22

Bacterial Cell Wall

The bacterial cell wall is an essential structural component that encases the plasma membrane, preserving cellular integrity, determining shape, and protecting against osmotic stress. This rigid yet flexible structure primarily comprises peptidoglycan, a polymer that forms a mesh-like matrix conferring mechanical strength and flexibility.Peptidoglycan Composition and StructurePeptidoglycan, the core of the bacterial cell wall, comprises alternating units of N-acetylglucosamine (NAG) and...
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

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...
Archaeal Cell Wall01:29

Archaeal Cell Wall

Archaeal cell walls are structurally and compositionally distinct from their bacterial counterparts, lacking the characteristic peptidoglycan layer found in most bacteria. Instead, archaeal cell walls exhibit remarkable diversity, utilizing materials such as pseudomurein, polysaccharides, and proteins to construct their protective outer layers. This structural flexibility is closely tied to archaea's ecological adaptability.S-Layers: The Common Archaeal Cell WallThe S-layer is the most...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...