The role of the <i>Staphylococcus lugdunensis</i> Isd system in iron acquisition and biofilm formation

Abstract

Staphylococcus lugdunensis is a coagulase negative staphylococcus (CoNS) that is part of the normal skin flora but unlike most CoNS S. lugdunensis has the capacity to cause aggressive and rapidly progressive infections. The molecular mechanisms that facilitate the transition of S. lugdunensis from a common commensal to an invasive pathogen remain poorly defined. Analysis of the S. lugdunensis genome indicates the presence of an iron-regulated surface determinant (Isd) system with unique features. For example, unlike the Staphylococcus aureus Isd system which encodes two paralogous heme oxygenases the Isd system within S. lugdunensis encodes a single heme oxygenase. Furthermore, the terminal gene within the S. lugdunensis Isd system encodes for a predicted peptidoglycan (PG) hydrolase. My dissertation research establishes that the S. lugdunensis Isd system is iron-regulated and includes both an IsdG-family heme oxygenase and peptidoglycan hydrolase. Additionally, I have demonstrated that S. lugdunensis IsdG degrades heme to staphylobilin designating it as the conserved IsdG-mediated heme degradation product. My research also established that the peptidoglycan hydrolase within the S. lugdunensis Isd system hydrolyzes PG, modulates the release of IsdC from the PG wall and facilitates biofilm formation. Together this work provides insight into how S. lugdunensis fulfills its nutritional requirements during infection as well as how S. lugdunensis forms biofilms.