Related Experiment Video
Updated: Aug 14, 2026
06:36
Improved Enzyme Protection Assay to Study Staphylococcus aureus Internalization and Intracellular Efficacy of Antimicrobial Compounds
Published on: September 8, 2021
Beta-lactam resistance in Staphylococcus aureus cells that do not require a cell wall for integrity
Elizabeth Fuller1, Catherine Elmer, Fiona Nattress
1University Hospital of North Durham, United Kingdom.
Antimicrobial Agents and Chemotherapy
|November 24, 2005
Summary
This study shows that Staphylococcus aureus can develop stable penicillin and methicillin resistance by growing with defective cell walls. This resistance occurs without typical resistance genes, suggesting a novel survival mechanism.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Antibiotic Resistance
Background:
- Staphylococcus aureus is a significant human pathogen.
- Antibiotic resistance in S. aureus poses a global health threat.
- Understanding novel resistance mechanisms is crucial for developing new treatments.
Purpose of the Study:
- To investigate the development of penicillin and methicillin resistance in Staphylococcus aureus.
- To characterize the mechanism of resistance in cell wall-defective variants.
- To explore the role of cell wall integrity in antibiotic resistance.
Main Methods:
- Generating cell wall-defective S. aureus using high osmolality medium and sublethal penicillin G.
- Assessing antibiotic resistance (penicillin, methicillin) post-antibiotic removal.
- Analyzing resistance mechanisms, including mecA, beta-lactamase, and pbp gene mutations.
- Evaluating cell wall properties and osmotic stability of resistant strains.
Main Results:
- S. aureus ATCC 9144 developed stable, homogeneous penicillin and methicillin resistance after growth in sublethal penicillin G.
- Resistance acquisition was enhanced by transient cell wall-defective growth.
- Resistant cells were mecA-negative, beta-lactamase-negative, and lacked pbp gene mutations.
- Resistant cells exhibited diffuse, lysostaphin-resistant, but Triton X-100-sensitive cell walls and osmotic stability independent of intact cell walls.
Conclusions:
- Staphylococcus aureus can acquire stable penicillin and methicillin resistance through a mechanism not dependent on typical resistance genes.
- Transient cell wall-defective growth facilitates the development of this novel resistance.
- These resistant cells are osmotically stable without an intact cell wall and can readily adapt to penicillin G presence.
Related Concept Videos
01:25Mechanism 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...
01:23Inhibitors 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...
01:22Bacterial 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...
01:30Development 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...
01:25Clinical 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...
01:29Archaeal 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...