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Updated: Oct 9, 2025
Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
Significant variability exists in the cytotoxicity of global methicillin-resistant Staphylococcus aureus lineages
Maisem Laabei1, Sharon J Peacock2, Beth Blane2
1Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK.
Abstract:
Staphylococcus aureus is a major human pathogen where the emergence of antibiotic resistant lineages, such as methicillin-resistant S. aureus (MRSA), is a major health concern. While some MRSA lineages are restricted to the healthcare setting, the epidemiology of MRSA is changing globally, with the rise of specific lineages causing disease in healthy people in the community. In the past two decades, community-associated MRSA (CA-MRSA) has emerged as a clinically important and virulent pathogen associated with serious skin and soft-tissue infections (SSTI). These infections are primarily cytotoxin driven, leading to the suggestion that hypervirulent lineages/multi-locus sequence types (STs) exist. To examine this, we compared the cytotoxicity of 475 MRSA isolates representing five major MRSA STs (ST22, ST93, ST8, ST239 and ST36) by employing a monocyte-macrophage THP-1 cell line as a surrogate for measuring gross cytotoxicity. We demonstrate that while certain MRSA STs contain highly toxic isolates, there is such variability within lineages to suggest that this aspect of virulence should not be inferred from the genotype of any given isolate. Furthermore, by interrogating the accessory gene regulator (Agr) sequences in this collection we identified several Agr mutations that were associated with reduced cytotoxicity. Interestingly, the majority of isolates that were attenuated in cytotoxin production contained no mutations in the agr locus, indicating a role of other undefined genes in S. aureus toxin regulation.
Insights
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes serious skin infections. Virulence varies greatly within MRSA lineages, and toxin production is not solely determined by genotype or accessory gene regulator (Agr) mutations.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen, with community-associated MRSA (CA-MRSA) strains causing severe skin and soft-tissue infections (SSTIs).
- CA-MRSA virulence is linked to cytotoxins, prompting investigation into hypervirulent lineages and sequence types (STs).
Purpose of the Study:
- To assess the cytotoxicity of major MRSA STs and identify factors influencing virulence.
- To determine if MRSA lineage or genotype can predict cytotoxicity and investigate the role of the accessory gene regulator (Agr) in toxin production.
Main Methods:
- Compared cytotoxicity of 475 MRSA isolates from five major STs using a THP-1 monocyte-macrophage cell line.
- Analyzed accessory gene regulator (Agr) sequences to identify mutations associated with altered cytotoxicity.
Main Results:
- Significant variability in cytotoxicity was observed within MRSA lineages, indicating genotype alone cannot predict virulence.
- Specific MRSA STs contained highly toxic isolates, but this was not a universal trait of the lineage.
- Several Agr mutations correlated with reduced cytotoxicity, but most attenuated isolates lacked Agr mutations, suggesting other regulatory genes are involved.
Conclusions:
- MRSA virulence, specifically cytotoxicity, is highly variable within lineages and cannot be reliably inferred from genotype.
- While Agr mutations can reduce MRSA cytotoxicity, other genetic factors play a significant role in regulating toxin production.
- Further research is needed to identify novel genes involved in S. aureus toxin regulation and virulence.
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