Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem around the world. In Australia, ST93-IV[2B] is the dominant CA-MRSA clone and displays significantly greater virulence than other S. aureus. Here, we have examined the evolution of...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
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Oxford University Press
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/41794 |
| _version_ | 1848756242625855488 |
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| author | Stinear, T. Holt, K. Chua, K. Stepnell, J. Tuck, K. Coombs, Geoffrey Harrison, P. Seemann, T. Howden, B. |
| author_facet | Stinear, T. Holt, K. Chua, K. Stepnell, J. Tuck, K. Coombs, Geoffrey Harrison, P. Seemann, T. Howden, B. |
| author_sort | Stinear, T. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem around the world. In Australia, ST93-IV[2B] is the dominant CA-MRSA clone and displays significantly greater virulence than other S. aureus. Here, we have examined the evolution of ST93 via genomic analysis of 12 MSSA and 44 MRSA ST93 isolates, collected from around Australia over a 17-year period. Comparative analysis revealed a core genome of 2.6 Mb, sharing greater than 99.7% nucleotide identity. The accessory genome was 0.45 Mb and comprised additional mobile DNA elements, harboring resistance to erythromycin, trimethoprim, and tetracycline. Phylogenetic inference revealed a molecular clock and suggested that a single clone of methicillin susceptible, Panton-Valentine leukocidin (PVL) positive, ST93 S. aureus likely spread from North Western Australia in the early 1970s, acquiring methicillin resistance at least twice in the mid 1990s. We also explored associations between genotype and important MRSA phenotypes including oxacillin MIC and production of exotoxins (α-hemolysin [Hla], δ-hemolysin [Hld], PSMα3, and PVL). High-level expression of Hla is a signature feature of ST93 and reduced expression in eight isolates was readily explained by mutations in the agr locus. However, subtle but significant decreases in Hld were also noted over time that coincided with decreasing oxacillin resistance and were independent of agr mutations. The evolution of ST93 S. aureus is thus associated with a reduction in both exotoxin expression and oxacillin MIC, suggesting MRSA ST93 isolates are under pressure for adaptive change |
| first_indexed | 2025-11-14T09:09:05Z |
| format | Journal Article |
| id | curtin-20.500.11937-41794 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:09:05Z |
| publishDate | 2014 |
| publisher | Oxford University Press |
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| spelling | curtin-20.500.11937-417942017-09-13T14:19:37Z Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus Stinear, T. Holt, K. Chua, K. Stepnell, J. Tuck, K. Coombs, Geoffrey Harrison, P. Seemann, T. Howden, B. comparative genomics alpha-hemolysin community-acquired MRSA Staphylococcus aureus Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem around the world. In Australia, ST93-IV[2B] is the dominant CA-MRSA clone and displays significantly greater virulence than other S. aureus. Here, we have examined the evolution of ST93 via genomic analysis of 12 MSSA and 44 MRSA ST93 isolates, collected from around Australia over a 17-year period. Comparative analysis revealed a core genome of 2.6 Mb, sharing greater than 99.7% nucleotide identity. The accessory genome was 0.45 Mb and comprised additional mobile DNA elements, harboring resistance to erythromycin, trimethoprim, and tetracycline. Phylogenetic inference revealed a molecular clock and suggested that a single clone of methicillin susceptible, Panton-Valentine leukocidin (PVL) positive, ST93 S. aureus likely spread from North Western Australia in the early 1970s, acquiring methicillin resistance at least twice in the mid 1990s. We also explored associations between genotype and important MRSA phenotypes including oxacillin MIC and production of exotoxins (α-hemolysin [Hla], δ-hemolysin [Hld], PSMα3, and PVL). High-level expression of Hla is a signature feature of ST93 and reduced expression in eight isolates was readily explained by mutations in the agr locus. However, subtle but significant decreases in Hld were also noted over time that coincided with decreasing oxacillin resistance and were independent of agr mutations. The evolution of ST93 S. aureus is thus associated with a reduction in both exotoxin expression and oxacillin MIC, suggesting MRSA ST93 isolates are under pressure for adaptive change 2014 Journal Article http://hdl.handle.net/20.500.11937/41794 10.1093/gbe/evu022 Oxford University Press fulltext |
| spellingShingle | comparative genomics alpha-hemolysin community-acquired MRSA Staphylococcus aureus Stinear, T. Holt, K. Chua, K. Stepnell, J. Tuck, K. Coombs, Geoffrey Harrison, P. Seemann, T. Howden, B. Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus |
| title | Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus |
| title_full | Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus |
| title_fullStr | Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus |
| title_full_unstemmed | Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus |
| title_short | Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus |
| title_sort | adaptive change inferred from genomic population analysis of the st93 epidemic clone of community-associated methicillin-resistant staphylococcus aureus |
| topic | comparative genomics alpha-hemolysin community-acquired MRSA Staphylococcus aureus |
| url | http://hdl.handle.net/20.500.11937/41794 |