Staphylococcus aureus toxins: expression and control

Thesis

Staphylococcus aureus was discovered in 1880 by the Scottish surgeon Sir Alexander Ogston. Its ability to utilise a panoply of secreted and cell associated virulence factors, combined with an ability to rapidly adapt to antibiotic selective pressure, has led it to become one of the most important Gram positive pathogens of our time. It plays a significant role in chronic diseases such as eczema, as well as the acute and potentially life threatening conditions toxic shock syndrome (TSS), meningitis, pneumonia and staphylococcal scalded skin syndrome (SSSS) to name just a few. Its presence in hospitals is endemic in many countries, where methicillin resistant S. aureus (MRSA) strains have earned the 'superbug' moniker.

Using a large, well-defined, clinical strain collection in combination with isogenic lab strains, this study endeavored to characterise the genetic factors associated with S. aureus toxicity, and identify novel means of controlling toxin expression.

We found that:

• A broad range of toxicities exists among S. aureus strains, that the beta- and delta-haemolysins are involved, and that hospital acquired-MRSA (HA-MRSA) strains are less toxic than MSSA or community acquired-MRSA (CA-MRSA).

• NaCl and the emollient Oilatum downregulate toxin expression.

• The mecA gene, conferring methicillin resistance, mediates mutation rates.

• The large type II SCCmec element of HA-MRSA confers a significant metabolic burden which is mitigated by the down regulation of toxins.

• The smaller type IV SCCmec element of CA-MRSA does not confer a significant metabolic burden, enabling CA-MRSA to utilise their full arsenal of virulence factors.

Authors: Collins, J

• Peer review status: Peer reviewed
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford