SCCmec is a large mobile genetic element that includes the mecA gene and confers resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA). There is evidence that SCCmec disseminates among staphylococci, but the transfer mechanisms are unclear. Here, we show that two-component systems mediate the upregulation of natural competence genes in S. aureus under biofilm growth conditions, and this enhances the efficiency of natural transformation. We observe SCCmec transfer via natural transformation from MRSA, and from methicillin-resistant coagulase-negative staphylococci, to methicillin-sensitive S. aureus. The process requires the SCCmec recombinase genes ccrAB, and the stability of the transferred SCCmec varies depending on SCCmec types and recipients. Our results suggest that natural transformation plays a role in the transfer of SCCmec and possibly other mobile genetic elements in S. aureus biofilms.
Linezolid resistance mediated by cfr vectors, such as pSCFS7-like plasmids, can be efficiently transferred to clinical MRSA in Japanese isolates. After reaching the staphylococcal pool, the cfr gene could be spread among MRSA strains by either conjugation or transduction.
Expression of genes required for natural genetic competence in Staphylococcus aureus is controlled by an alternative transcription sigma factor, SigH. However, even in the SigH-expressing cells, the DNA transformation efficiency varies depending on culture conditions. We report here that cells grown in the competence-inducing medium (CS2 medium) exhibit enlarged morphology with disintegrated cell walls. Notably, an autolysis inhibitor, Sodium Polyanethol Sulfonate (SPS), facilitated transformation in CS2 medium in a dose-dependent manner, suggesting the involvement of the cell wall metabolism in transformation. However, the transformation efficiency of cells grown in TSB was not improved by physical or enzymatic damage on the cell walls.
Methicillin-resistant Staphylococcus aureus (MRSA) carries the resistance gene mecA in the staphylococcal cassette chromosome (SCC) that disseminates among staphylococci but the cell-to-cell transmission mechanism of SCC has not been clarified for half a century1. Here, we present evidence for efficient natural transformation in Staphylococcus aureus and its relevance in SCCmec transmission. We found that growth in biofilm conditions increased the transformation efficiency in a dependent manner on two component signal transduction systems, TCS13 (AgrCA) and TCS17 (BraSR). Strikingly, we demonstrate that natural transformation mediates the transfer of SCCmec from MRSA or methicillin-resistant coagulase negative staphylococci to methicillin-sensitive S. aureus. The site-specific insertion/excision system mediated by cassette chromosome recombinases was essential for SCCmec transformation while the stability of SCCmec varied depending on SCC types and recipients. We propose that natural transformation is the key process in the emergence of MRSA.
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