Transcriptional Analysis of the Streptococcus pyogenes Salivaricin Locus

Abstract

The sal lantibiotic locus plays an important role in the virulence of Streptococcus pyogenes. Our transcriptional analysis of the sal locus provides new information on the complex regulation of this operon. Transcription of the operon is regulated by a promoter upstream of the operon and by a second internal promoter upstream of the salKRZ genes. Here we identify the location of the internal promoter and provide information on how this promoter is autoregulated by proteins within the locus. We determined by primer extension that the salKR promoter is located within the salY gene and identified several regulatory regions important for expression. The higher activity of the promoter in a salKR deletion strain indicates a role in repression by the SalR response regulator. Further, this promoter had higher activity in a salA deletion strain, implicating corepression or a signaling role for the SalA peptide. Finally, we demonstrate that this promoter can be controlled by host factors. Analysis of transcriptional regulation of this locus provides a better understanding of the function of the sal locus in S. pyogenes pathogenesis.

Identification of Burkholderia pseudomallei Genes Induced During Infection of Macrophages by Differential Fluorescence Induction

“…However, it is possible that the gene annotation is incorrect or that an internal promoter is present. Internal promoters have been reported in a range of bacteria (Miyata et al, 2013;Namprachan-Frantz et al, 2014;Perault and Cotter, 2018). For example, the Streptococcus pyogenes salivaricin (sal) operon is regulated by a promoter upstream of the operon and also by a second promoter located within the operon (Namprachan-Frantz et al, 2014).…”

“…Internal promoters have been reported in a range of bacteria (Miyata et al, 2013;Namprachan-Frantz et al, 2014;Perault and Cotter, 2018). For example, the Streptococcus pyogenes salivaricin (sal) operon is regulated by a promoter upstream of the operon and also by a second promoter located within the operon (Namprachan-Frantz et al, 2014). Internal promoters are also found in genes encoding immunity proteins of Vibrio cholerae, which are independently expressed of other proteins encoded within the same operon (Miyata et al, 2013).…”

Quorum sensing in group A Streptococcus

“…The ability to produce mature bacteriocins is not widespread amongst all GAS isolates, and in most cases conserved mutations have occurred in biosynthetic loci. This has led authors to hypothesize that some of these circuits may have lost their lantibiotic and QS ability and instead have adapted them to perform other functions (Phelps and Neely, 2007 ; Namprachan-Frantz et al, 2014 ). One lantibiotic locus present in GAS is orthologous to Salivaracin A (SalA) synthesis gene clusters.…”

“…Reinforcing this idea, mutating the SalA maturation genes in the immune strain T11 renders it sensitive to SalA. Some GAS strains possess all the genes of the sal cluster (MGAS10750, MGAS315, HSC5, SSI-1), although point mutations in maturation and transport genes may still render these strains unable to produce the active lantibiotic and are sensitive to its activity (Wescombe et al, 2006 ; Phelps and Neely, 2007 ; Namprachan-Frantz et al, 2014 ). Evidence has suggested however that the sal locus may still play a role during GAS infection in the host.…”

“…Therefore, it has been hypothesized that GAS SalY may have changed and adapted to bind and/or export other substrates. It has also been shown that salA expression is upregulated during murine muscle tissue infection, and recently it also was shown that human serum increases the expression of the promoter upstream of the salRK TCS genes, providing a possible link between host factors and activation of the sal locus in GAS (Loughman and Caparon, 2006a ; Namprachan-Frantz et al, 2014 ). In addition, data have suggested that mutations in the salRK TCS can affect other genes outside the sal cluster of genes in GAS and other streptococci (Li et al, 2008 ; Le Breton et al, 2013 ).…”