Protease Networks And Pathway Interconnectivity In Gram-Positive Bacteria

The emergence of Gram‐positive drug resistant bacteria such as methicillin‐resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae and Enterococcus represent a serious public health problem. Novel drug targets are needed and bacterial proteases are potential candidates as they are implicated in virtually every important biological process. To understand how proteases participate in pathology, it is important to elucidate the degradome, its function and its effect on biological networks. With this goal, we are developing a comprehensive computational model of protease networks and pathway interconnectivity of multiple Gram‐positive bacteria using Pathway Logic. Pathway Logic is a systems biology approach to biological processes as integrated systems rather than isolated parts based on formal methods and rewriting logic. As an initial step, we developed a model of interaction networks with 30 proteases from 7 different Gram‐positive bacteria. Our results demonstrate interconnectivity between proteases. The comparison feature of Pathway Logic tool identified key proteases participating in multiple pathways within a large network and across multiple networks that could be “choke points”. Our results suggest novel roles for proteases that need to be validated using experimental methods. This research is supported by funding to SRI International from the Commonwealth of Virginia.