All ETDs from UAB

Advisory Committee Chair

Terje Dokland

Advisory Committee Members

Suzanne M Michalek

Peter E Prevelige Jr

Jamil S Saad

Hui Wu

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Staphylococcus aureus is known to cause disease in both human and animal populations. Many of the virulence factors important for S. aureus pathogenesis are found on mobile genetic elements known as S. aureus pathogenicity islands (SaPIs). SaPIs can transduce into surrounding cells, giving those cells the ability to produce virulence factors. Derepression allows SaPIs to be excised from S. aureus genome to initiate mobilization. Derepressors have been identified for multiple SaPIs, but it remains unknown if the same SaPI can be derepressed by multiple derepressors. It has been shown that SaPIbov1 can be derepressed by the type 1 dUTPase from 80α and φ11 helper phages through interaction with SaPIbov1 Stl (Stlbov1), the SaPI repressor. We previously noted that φNM1 can transduce SaPIbov1, although it lacks a type 1 dUTPase. The purpose of this study was to determine if SaPIbov1 could be derepressed by an analogous protein, and if it has similar interactions with Stlbov1 as type 1 dUTPase. We identified the derepressor as a type 2 dUTPase encoded by φNM1 (DutNM1), which interacted directly with Stlbov1. This interaction causes release of the promoter needed for expression of excisionase and integrase. Even though the structures of type 1 and type 2 dUTPases are completely different, they are still able to interact with Stlbov1. Stlbov1 interaction with DutNM1 inhibits enzyme activity. Since the ability to hydrolyze dUTP is a common function to the two different types of dUTPases, we hypothesized that it was integral to the interaction with Stlbov1. Interestingly, the inactive mutants show this is not the case, because they are able to interact with Stlbov1. Only the null activity mutant lacking all hypothetical Mg2+ binding residues of DutNM1 fails to cause Stlbov1 to release the promoter. It is possible that the Mg2+ binding or those conserved residues of DutNM1 are important for Stl to release the promoter. This work has thus identified a novel derepressor and so provides an enhanced understanding of the derepression mechanisms of SaPIs.



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