Comparative proteomic investigation of multiple methicillin-resistant Staphylococcus aureus strains generated through adaptive laboratory evolution
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Updated: Oct 22, 2025
Procedure for Adaptive Laboratory Evolution of Microorganisms Using a Chemostat
Published on: September 20, 2016
Jordy Evan Sulaiman1, Lexin Long2, Long Wu1
1Department of Chemical and Biological Engineering, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong.
Abstract:
Recent discoveries indicate that tolerance and resistance could rapidly evolve in bacterial populations under intermittent antibiotic treatment. In the present study, we applied antibiotic combinations in laboratory experiments to generate novel methicillin-resistant Staphylococcus aureus strains with distinct phenotypes (tolerance, resistance, and suppressed tolerance), and compared their proteome profiles to uncover the adaptation mechanisms. While the tolerant strains have very different proteomes than the susceptible ancestral strain, the resistant strain largely resembles the ancestral in terms of their proteomes. Our proteomics data and other assays support the connection between the detected mutations to the observed phenotypes, confirming the general understanding of tolerance and resistance mechanisms. While resistance directly counteracts the action mechanism of the antibiotic, tolerance involves complex substantial changes in the cells' biological process to achieve survival advantages. Overall, this study provides insights into the existence of diverse evolutionary pathways for tolerance and resistance development under different treatment scenarios.
Insights
Bacterial tolerance and resistance to antibiotics evolve rapidly. This study found that while resistant strains resemble ancestral bacteria, tolerant strains undergo significant proteome changes, revealing diverse evolutionary adaptation mechanisms.
Area of Science:
- Microbiology
- Evolutionary Biology
- Biochemistry
Background:
- Antibiotic resistance and tolerance are critical challenges in bacterial infections.
- Intermittent antibiotic treatment can accelerate the evolution of bacterial survival strategies.
- Understanding the molecular mechanisms underlying these adaptations is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the proteomic differences between methicillin-resistant Staphylococcus aureus (MRSA) strains exhibiting tolerance, resistance, and suppressed tolerance.
- To elucidate the adaptation mechanisms driving the evolution of antibiotic tolerance and resistance.
- To compare the evolutionary pathways leading to distinct antibiotic survival phenotypes.
Main Methods:
- Laboratory evolution experiments using antibiotic combinations to generate MRSA strains with specific phenotypes.
- Proteome profiling of ancestral, tolerant, and resistant MRSA strains.
- Genomic analysis to identify mutations correlated with observed phenotypes.
Main Results:
- Tolerant MRSA strains displayed significantly altered proteomes compared to the susceptible ancestral strain.
- Resistant MRSA strains showed proteome profiles largely similar to the ancestral strain.
- Proteomics data and mutation analysis confirmed the link between genetic changes and phenotypic outcomes.
Conclusions:
- Antibiotic resistance and tolerance involve distinct evolutionary pathways and molecular adaptations.
- Tolerance necessitates substantial cellular biological process alterations for survival, unlike resistance.
- This study highlights diverse evolutionary strategies bacteria employ to survive antibiotic pressure.
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