Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


Staats_Dissertation-Final.pdf (7.85 MB)

ETD Abstract Container

Abstract Header

The kinetics and pathogenic implications of synovial fluid-induced Staphylococcus aureus aggregate formation in the development of periprosthetic joint infections

Staats, Amelia Margaret
http://orcid.org/0000-0001-7563-1403
http://rave.ohiolink.edu/etdc/view?acc_num=osu1668420138260744

Abstract Details

2022, Doctor of Philosophy, Ohio State University, Microbiology.
Orthopedic procedures significantly enhance the quality of life for hundreds of thousands of people each year. Despite these profound medical advances, a primary risk of any invasive surgery is still the development of an infection. The implantation of medical hardware, which is associated with joint replacement procedures, dramatically increases the chances of biofilm formation at the postsurgical site. For several reasons, bacterial biofilm formation on an implanted device, or adjacent tissue, severely complicates the resolution of an infection. Because antibiotic treatment is highly ineffective against biofilm-implicated infections, patients are often subjected to a secondary surgery to debride and remove the hardware. While current treatment methods are surgeon-specific, most revision protocols include surgical explantation, rigorous antibiotic therapy, and eventual re-implantation surgery. There is an urgent need for novel methods of prevention and treatment for periprosthetic joint infections. To develop effective, targeted strategies, it is imperative that we first understand the underlying mechanisms by which bacterial pathogens enter, proliferate, and establish in the postsurgical joint space. While several bacterial pathogens have been found to invade the postoperative joint environment, including gram-positive and gram-negative species, Staphylococcus aureus is one of the most common and virulent. In establishing a chronic infection, S. aureus engages a wide range of virulence factors- including biofilm establishment, host polymer binding, and a range of secreted toxins. To date, investigations probing the bacterial pathogenesis of periprosthetic joint infections have primarily centered around biofilms. Although the generalized stages of biofilm formation have been well defined for decades, the mechanisms through which the invading bacteria survive initial entry into a specific host environment are highly variable. The post-operative joint does not provide an easy environment for incoming bacteria to begin the relatively lengthy process of biofilm formation. Fluid shear, host immune cells, and applied antibiotics target the susceptible incoming cells immediately upon entry into the joint. Our group, among others, speculated that in order to survive long enough in such an inhospitable environment, the bacteria must engage an instantaneous method of conferring protection. Upon contact with synovial fluid, the viscous fluid filling the joint cavity, S. aureus will rapidly form bacterial aggregates. Aggregate formation has been widely recognized as a protective state in many systems, we therefore hypothesized the synovial fluid-induced aggregation likely enhances bacterial survival in the context of periprosthetic joint infection development. Considering the highly dynamic nature of the post-operative joint environment, we systematically evaluated the key host and bacterial factors which mediate aggregate formation in synovial fluid. Further, we assessed various synovial fluid aggregate phenotypes, which arise from distinct mechanisms, for their tolerance against antibiotic challenge. Taken together, this dissertation provides a summation of the scope, underlying mechanisms, and pathogenic implications of synovial fluid-induced aggregation of S. aureus.
Paul Stoodley (Advisor)
John Gunn (Committee Member)
Daniel Wozniak (Committee Member)
Chad Rappleye (Committee Member)
207 p.
Microbiology
Orthopedic infection, Bacterial pathogenesis, Synovial Fluid, Aggregation

Recommended Citations

Citations

  • Staats, A. M. (2022). The kinetics and pathogenic implications of synovial fluid-induced Staphylococcus aureus aggregate formation in the development of periprosthetic joint infections [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1668420138260744

    APA Style (7th edition)

  • Staats, Amelia. The kinetics and pathogenic implications of synovial fluid-induced Staphylococcus aureus aggregate formation in the development of periprosthetic joint infections. 2022. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1668420138260744.

    MLA Style (8th edition)

  • Staats, Amelia. "The kinetics and pathogenic implications of synovial fluid-induced Staphylococcus aureus aggregate formation in the development of periprosthetic joint infections." Doctoral dissertation, Ohio State University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=osu1668420138260744

    Chicago Manual of Style (17th edition)

osu1668420138260744
137
© 2022, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.