Expression of toxic shock syndrome toxin-1 by epidemic meticillin-resistant Staphylococcus aureus 16

Abstract

BackgroundStaphylococcal toxic shock syndrome (TSS) is a fatal illness attributed to Staphylococcus aureus toxic shock syndrome toxin-1 (TSST-1), encoded by the tst gene. No epidemiological data on TSS exist from the UK. Strains of S aureus may carry the tst gene but not cause TSS, such as the UK strain epidemic meticillin-resistant SA-16 (EMRSA-16). The aim of this study was to determine the epidemiology of TSS in the UK and investigate the expression of TSST-1 by EMRSA-16 and tst+ meticillin-sensitive S aureus (MSSA). MethodsCases of TSS were identified at the UK Health Protection Agency (HPA) and epidemiological features analysed. A selection of clonal complex (CC)-30 EMRSA-16 and TSS-associated MSSA strains was chosen for investigation. The tst gene and promoter region were sequenced in all strains. The staphylococcal pathogenicity island (SaPI) harbouring tst was determined by PCR. Growth of strains in brain heart infusion broth was monitored by optical density (OD600). TSST-1 in supernatants was quantified by western blot using densitometry according to a TSST-1 standard curve. RNA was isolated for tst transcript analysis by quantitative reverse-transcription-PCR (qRT-PCR). Whole genome sequencing was performed on all strains to identify potential mutations in known regulators of toxin synthesis. Findings150 cases of TSS were reported to the HPA over a period of 4 years. Six cases (4%) were attributable to MRSA and the remainder to MSSA. There was no difference in the tst gene or promoter sequence among the strains and tst was carried by SaPI2. TSST-1 production by EMRSA-16 strains commenced earlier in growth than did MSSA strains and was greater in TSS-associated MSSA than in EMRSA-16 strains throughout growth. These results were compared with tst transcription by MSSA and EMRSA16 using qRT-PCR. InterpretationEMRSA-16 produces less TSST-1 than does MSSA of the same lineage; this may be due to differences in global gene regulators, perhaps as a result of changes in PBP2a expression, or the carriage of a large SCCmec element by EMRSA-16. This difference in production may explain the paucity of TSS cases caused by MRSA. FundingUK National Centre for Infection Prevention and Management.