Urinary tract infections (UTIs) constitute a tremendous public health burden estimated at $2.5 billion annually in the United States alone. The biofilm producing bacterium Escherichia coli (E. coli) is by far the most frequent causative agent of UTIs and is increasingly becoming antibiotic resistant. In order to develop more effective antimicrobial therapies, we must first understand the mechanisms by which these bacteria invade the host and defend themselves. Recently developed crosslinking-based mass spectrometry (XL-MS) approaches have the potential to revolutionize high-throughput mapping of protein-protein interactions (PPIs) due to: their lower false discovery rate, their ability to detect weak or transient interactions that may be missed with techniques like immuno-precipitation or affinity purification, and their ability to be applied in vivo under physiological conditions. Our goal is to further optimize the information that can be obtained from XL-MS data, by not only determining the identities of the residues in each protein that are interacting with partner proteins, but additionally, by building three-dimensional models of the interacting protein complexes informed by the XL-MS data. This would provide us with a powerful additional source of information regarding PPIs in any system of interest, allowing us to supplement proteomic profiling of microbial communities with experimentally derived, quaternary structural models of the identified statistically significant PPIs. Preliminary applications of our approaches to E. coli UTI89 biofilms provided quaternary structures consistent with existing high-resolution experimental data (where available), and also information on dozens of additional complexes potentially involved in biofilm development. We expect application of the tools developed during the course of this work will inform antimicrobial therapeutic development by allowing rapid identification of statistically key nodes in the protein-protein interactome of pathogenic bacterial strains such as E. coli UTI89.