SigmaB regulates ccrAB expression and SCCmec excision in methicillin-resistant Staphylococcus aureus

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide pathogen that is resistant to practically the entire class of β-lactam antibiotics due to the presence of the mecA gene. The mecA gene is located on a large mobile genetic element referred to as staphylococcal cassette chromosome mec (SCCmec), and the excision and integration of SCCmec are mediated by the Ccr recombinase encoded by ccrAB or ccrC, which are also located on SCCmec. Previous studies have shown that the ccrAB genes are only expressed in a minority of cells and that their expression levels can be affected by certain environmental stimuli, but the molecular mechanisms controlling these phenotypes remain elusive. Here, we found that overexpression of SigB can dramatically enhance ccrA transcription and SCCmec excision in MRSA strain N315, revealing an important role for this alternative sigma factor in the lateral transfer of SCCmec. Further primer extension-blot analysis and 5′RACE (Rapid Amplification of cDNA Ends) indicated that an unrecognized SigB-dependent promoter region, which exists in certain SCCmec type II and IV strains, is responsible for the enhancement, and the ccrAB genes are in fact transcribed in a two-promoter pattern with a low activity of the SigB-dependent promoter under normal growth conditions.