| Popis: |
Antibiotic resistant strains of S. aureus are responsible for hospital-acquired infections around the world, and also cause serious infections in the wider community, thereby posing a serious threat to human health. Resistance genes may be chromosomally encoded and/or carried by one or more plasmids. Efficient partitioning of replicated chromosomes and plasmids ensures their faithful inheritance. The S. aureus chromosome carries a putative partitioning gene, parB, and predicted parS sites at which ParB might act. Analysis of a S. aureus parB mutant revealed an increased frequency of anucleate cell production under some conditions. ParB was also shown to bind specifically to three parS sites. The partitioning system of the S. aureus multiresistance plasmid pSK41 comprises two genes in an operon, parM and parR, and a centromere site, parC. ParM interacts with ParR bound to parC repeats to form a partitioning complex. Binding of ParR to parC also mediates transcriptional autoregulation of the operon. Results described here indicate that the minimal parC region required for function is larger than anticipated. The pSK41 orf86 gene is located upstream of the replication initiation gene, rep, but its function was a mystery. Orf86 was shown to negatively regulate rep expression. It repressed transcription from the rep promoter, and reduced the copy number of pSK41 mini-replicons. Transcription of orf86 is dependent on transcripts from the RNAI promoter, which therefore mediates the production of two RNA species that regulate rep expression; a small antisense transcript RNAI that inhibits Rep translation, and orf86 mRNA that is translated into Orf86, which inhibits rep transcription. Based on its newly described role in copy number control, orf86 was renamed cop. Detailed knowledge about DNA replication and segregation mechanisms arising from these studies may contribute to the development of strategies to combat the threat of antibiotic resistant S. aureus. |
