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Multiplex PCR Assay for Typing of Staphylococcal Cassette Chromosome Mec Types I to V in Methicillin-resistant Staphylococcus aureus
Published on: September 5, 2013
Formation of CO2-dependent small-colony variants (SCVs) in methicillin-resistant Staphylococcus aureus mediated by a
Sisi Chen1,2, Wanyang Dong2, Song Li1
1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Clinical Laboratory/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510180, China.
Introduction:
Staphylococcus aureus is a major human pathogen and the emergence of small colony variants (SCVs) makes the treatment of S. aureus infections more challenging. The mechanism of CO2-dependent SCVs (CO2-SCVs) remains inadequately explored.
Methods:
In this study, a clinical CO2-SCV strain (GY8) and a normal strain (GY9) were characterized from a patient with long-term infection. Through whole-genome sequencing, we detected a point mutation (H607Y) in the mpsB gene associated with the SCV phenotype. Transcriptomic profiling of both strains was performed to identify key genes or pathways closely related to SCV formation, followed by functional validation.
Results:
The mpsB (H607Y) mutant exhibited typical SCV characteristics, including reduced growth rate, decreased pigmentation, and increased aminoglycoside resistance. Compared to GY9, the SCV strain GY8 showed attenuated virulence but enhanced intracellular persistence, facilitating chronic infection. Additionally, the mutant displayed heightened sensitivity to Triton X-100 induced cell lysis, though electron microscopy revealed significant changes in cell wall thickness.under ambient air. Finally, protein structure prediction and molecular docking analysis revealed that the H607 residue likely serves as the active center of MpsB, providing new mechanistic insights into the formation of CO2-SCVs.
Conclusion:
Our findings demonstrate that a single mpsB mutation drives SCV emergence, highlighting its role in persistent infections and providing potential targets for therapeutic intervention.
Insights
A single mutation in the mpsB gene causes Staphylococcus aureus to form CO2-dependent small colony variants (CO2-SCVs). These SCVs persist in the host, aiding chronic infections and offering potential therapeutic targets.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogen Research
Background:
- Staphylococcus aureus is a significant human pathogen.
- Small colony variants (SCVs) of S. aureus complicate infection treatment.
- The mechanisms behind CO2-dependent SCVs (CO2-SCVs) are not well understood.
Purpose of the Study:
- To investigate the genetic basis and characteristics of CO2-SCVs.
- To identify key genes and pathways involved in CO2-SCV formation.
- To explore potential therapeutic targets for S. aureus SCV infections.
Main Methods:
- Whole-genome sequencing of clinical CO2-SCV and normal strains.
- Transcriptomic profiling to identify differentially expressed genes.
- Functional validation of identified mutations and pathways.
Main Results:
- A point mutation (H607Y) in the mpsB gene was linked to the CO2-SCV phenotype.
- The mpsB mutant showed reduced growth, pigmentation, and increased antibiotic resistance.
- SCVs exhibited enhanced intracellular persistence and altered cell wall structure.
- Structural analysis provided mechanistic insights into MpsB function in CO2-SCV formation.
Conclusions:
- A single mpsB mutation is sufficient to induce the CO2-SCV phenotype.
- CO2-SCVs play a role in persistent S. aureus infections.
- The mpsB gene and its associated pathways are potential targets for novel therapeutics.
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