Significant variability exists in the cytotoxicity of global methicillin-resistant Staphylococcus aureus lineages.
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Authors
Laabei, Maisem
Peacock, Sharon J
Blane, Beth
Baines, Sarah L
Howden, Benjamin P
Stinear, Timothy P
Massey, Ruth C
Publication Date
2021-12Journal Title
Microbiology (Reading)
ISSN
1350-0872
Publisher
Microbiology Society
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Laabei, M., Peacock, S. J., Blane, B., Baines, S. L., Howden, B. P., Stinear, T. P., & Massey, R. C. (2021). Significant variability exists in the cytotoxicity of global methicillin-resistant Staphylococcus aureus lineages.. Microbiology (Reading) https://doi.org/10.1099/mic.0.001119
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.
Keywords
Cytotoxicity, Staphylococcus aureus, Bacterial Virulence, Bacterial Pathogenesis
Sponsorship
Wellcome Trust (212258/Z/18/Z)
Identifiers
34928202, PMC8744995
External DOI: https://doi.org/10.1099/mic.0.001119
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333247
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