Current Research and Intellectual Property advancement in the laboratory focuses on bacterial infections that result (paradoxically) from the use of antibiotics. Our studies are performed under a One Health strategy that aims to expand interdisciplinary collaboration in diverse aspects of healthcare for humans and other animals. Our VA and University Affiliate teams are thus focused on elucidating pathogenic mechanisms in the anaerobic human and veterinary pathogen Clostridioides difficile, as well as the diarrheal disease organisms Enteropathogenic and Enterohemorrhagic E. coli. Ongoing studies include comprehensive epidemiological and mechanistic interrogation of C. difficile infection (CDI). Specifically, we have (1) prospective CDI surveillance in Southern Arizona VA and non-VA hospitals that has resulted in one of the only curated, fingerprinted and fully- cataloged C. difficile biorepositories in the Southwestern US; (2) developed precision genomics and proteomics approaches to identify factors contributing to the heightened virulence of newer strains of C. difficile; and (3) leveraged the information from (1) and (2) to develop multiple, novel C. difficile anti-infectives including targeted and bio-controlled live biotherapeutics as well as narrow-spectrum antimicrobials. Our VA Merit awards have resulted in one issued, and two Provisional, Patents as of December 2020. There are two over-arching goals of the activities described above. The first is to improve the health of Veterans and, indeed, the elderly and immunocompromised, by developing safe, oral, cost-effective anti-infective technologies that can transition expediently from the pre-clinical pipeline and into the community. The second is to continue to partner with VA, national and international Collaborators and train mentees such that current efforts can be channeled into a legacy plan for anti-infective research both at the SAVAHCS station as well as the University Affiliate. This renewal RCS application is thus envisaged as critical to the continued building of relationships within and outside the Southern Arizona VA Healthcare System community. Our research record underscores the power of cross-disciplinary science, and the RCS platform has enabled engagement with diverse research groups and fostered new avenues of investigation. Core values that have been cultivated via these collaborations include active listening, inclusive discussion and thoughtful communication. Training and Mentoring is an integral aspect of the PIs’ professional vision, and the current RCS cycle has provided opportunities to work with diverse and outstanding trainees and mentees. These have included (and continue to include) first-generation college students, members of under-represented minorities, early-career Faculty, and Physician-Scientist trainees. Taken together, RCS activities are envisioned to continue fostering focused and substantive contributions to the betterment of Veterans’ health via the...