Control of Staphylococcus aureus pathogenicity island excision

Abstract

SummaryStaphylococcus aureus pathogenicity islands (SaPIs) are a group of related 15-17 kb mobile genetic elements that commonly carry genes for superantigen toxins and other virulence factors. The key feature of their mobility is the induction of SaPI excision and replication by certain phages and their efficient encapsidation into specific small-headed phage-like infectious particles. Previous work demonstrated that chromosomal integration depends on the SaPI-encoded recombinase, Int. However, although involved in the process, Int alone was not sufficient to mediate efficient SaPI excision from chromosomal sites, and we expected that SaPI excision would involve an Xis function, which could be encoded by a helper phage or by the SaPI, itself. Here we report that the latter is the case. In vivo recombination assays with plasmids in Escherichia coli demonstrate that SaPI-coded Xis is absolutely required for recombination between the SaPI att L and attR sites, and that both sites, as well as their flanking SaPI sequences, are required for SaPI excision. Mutational analysis reveals that Xis is essential for efficient horizontal SaPI transfer to a recipient strain. Finally, we show that the master regulator of the SaPI life cycle, Stl, blocks expression of int and xis by binding to inverted repeats present in the promoter region, thus controlling SaPI excision.

Derepression of SaPIbov1 Is Independent of φNM1 Type 2 dUTPase Activity and Is Inhibited by dUTP and dUMP

“…It allows for the SaPI to be excised from the genome [30]. If the SaPI fails to be excised when the bacterial cell lyses due to the phage infection, then the SaPI can only be transferred by general transduction, which is at least 1000-fold less efficient than specialized transduction [32, 41]. This would limit the spread of virulence genes to the surrounding cells.…”

Bacteriophage-mediated spread of bacterial virulence genes

“…They are 15 kb mobile elements that encode virulence factors and are parasitic on certain temperate (helper) phages. Specific phage proteins are required to lift their repression [37,38 ], thereby initiating their excision [33,39] and replication [40]. A SaPIcoded small terminase subunit (TerS SP ) then complexes with the phage-coded large terminase subunit to enable packaging of SaPI DNA in small capsids composed of phage-derived virion proteins.…”

The Type 2 dUTPase of Bacteriophage ϕNM1 Initiates Mobilization of Staphylococcus aureus Bovine Pathogenicity Island 1

“…1), which is highly divergent between different SaPIs. In the presence of a compatible helper phage entering lytic cycle, Stl is derepressed by binding to a helper phage protein, leading to SaPI excision, replication, and interference with phage functions [14, 19, 20] (Fig. 1).…”