Alternative Sigma Factor σ~H Modulates Prophage Integration And Excision In Staphylococcus Aureus

The prophage is one of the most important components of variable regions in bacterial genomes. Some prophages carry additional genes that may enhance the toxicity and survival ability of their host bacteria. This phenomenon is predominant in Staphylococcus aureus, a very common human pathogen. Staphylococcus aureus is a widely distributed opportunistic pathogen causing numerous foreign-body-associated infections. Many staphylococcal phages contain genes that encode virulence factors which greatly enhance the bacterial invasiveness and help to evade host immunity in organic infection. The transfer of toxic genes by a lysogenic bacteriophage, or phage conversion, is an important mechanism in the evolution of virulent S. aureus strains. In S. aureus, only four sigma factors have been identified to date:the housekeeping sigma factorσA, and three alternative sigma factorsσB,σH, and the newly defined as. The S. aureusσH protein is a homolog of B. subtilisσH, which regulates sporulation-related genes.Bioinformatics analysis of several staphylococcal prophages revealed a highly conserved 40-bp untranslated region upstream of the int gene. A small transcript encoding phage integrase was identified to be initiated from the region, demonstrating that the untranslated region contained a promoter for int. No typical recognition sequence for eitherσA orσB was identified in the 40-bp region. Experiments both in vitro and in vivo demonstrated thatσH recognized the promoter and directed transcription. Genetic deletion of sigH altered the int expression, and subsequently, the excision proportion of prophage DNAs. Phage assays further showed that sigH affected the ability of spontaneous lysis and lysogenization in S. aureus, suggesting that sigH plays a role in stabilizing the lysogenic state. The recruitment of a host-source sigma factor for integration modulation may provide the prophage with a novel strategy to sense the host conditions and further influence prophage gene expression and correlative bacterial virulence. These findings revealed a novel mechanism of prophage integration specifically regulated by a host-source alternative sigma factor.This mechanism suggests a co-evolution strategy of staphylococcal prophages and their host bacteria.