Author ORCID Identifier
https://orcid.org/0009-0008-4375-6760
Date of Graduation
5-2026
Document Type
Thesis (MS)
Program Affiliation
Microbiology and Infectious Diseases
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Heidi B. Kaplan
Committee Member
Catherine G. Ambrose
Committee Member
Souvik Bhattacharya, PhD
Committee Member
Mary C. Farach-Carson, PhD
Committee Member
Anne-Marie Krachler, PhD
Committee Member
Jennifer N. Walker, PhD
Abstract
The rise of multidrug-resistant (MDR) infections is a growing concern in the treatment of deep musculoskeletal infections (MSKIs) and orthopaedic device-related infections (ODRIs). Staphylococcus aureus is responsible for about one third of these infections due to its strong biofilm forming capacity, presence on human skin, and the large number of antibiotic-resistant variants. Bacteriophage (phage) therapy is now being considered as a treatment for MDR MSKIs/ODRIs. We are investigating the use of phage encapsulated into or adsorbed onto biodegradable microspheres for local delivery to the site of these MDR infections. We determined that the anti-staphylococcal phage K effectively lyses the S. aureus osteomyelitis clinical isolate UAMS-1 growing in liquid culture, on agar plates, and as an in vitro biofilm. Our in vitro biofilm model using S. aureus UAMS-1 closely mimics the bone infection environment. To investigate if UAMS-1, which was isolated from an osteomyelitis infection in 1995, remains representative of current MSKI isolates, we characterized 63 S. aureus MSKI clinical isolates from our MSKI biorepository, which includes 23 methicillin-resistant S. aureus (MRSA) strains, by assessing biofilm formation in nutrient broth and synthetic interstitial fluid, and antibiotic and phage susceptibility. The UAMS-1 strain is resistant to only one antibiotic (penicillin), whereas the recently isolated strains show variable resistance profiles, from seven being sensitive to all antibiotics tested to one being resistant to 12 antibiotics. I analyzed the whole genome sequence of 59 of the clinical isolates and UAMS-1 to identify genetic differences related to biofilm formation, antibiotic and phage resistance. We determined that UAMS-1 adequately models current clinical MRSA infections based on its intermediate biofilm formation, resistance to a beta-lactam antibiotic, susceptibility to the Myoviridae phage in our library, and genomic analysis. This study may provide insights into phage biofilm disruption strategies.
Recommended Citation
Luna, Raquel C., "Characterization of Staphylococcus aureus Clinical Isolates from Deep Musculoskeletal Infections for an In Vitro Biofilm Model for Phage Therapy" (2026). Dissertations & Theses (Open Access). 1531.
https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1531
Keywords
Biofilm, Phage Therapy, Staphylococcus aureus, Musculoskeletal