Browsing by Subject "Staphylococcus aureus"
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Item Exploring a Novel, Non-Invasive Treatment for Prosthetic Joint Infection(2018-01-23) Narayanan, Ajay; Wang, Qi; Pybus, Christine; Shaikh, Sumbul; Munaweera, Imalka; Sturge, Carolyn; Chopra, Rajiv; Greenberg, DavidPeriprosthetic joint infection (PJI) is a very prevalent consequence of implant surgery. The surface of the prosthesis provides a favorable environment for the growth of bacterial biofilms, which are notorious for being resistant to conventional antibiotics. The current treatment for PJI involves re-opening the surgical site and replacing the prosthesis, a very costly procedure that diminishes patient quality of life. Recently, a non-invasive procedure has been developed that utilizes high frequency alternating magnetic fields (AMF) to destroy biofilms via induction heating. Our research was focused on both optimizing and further characterizing the cytotoxicity of this treatment method on Staphylococcus aureus and Pseudomonas aeruginosa, two biofilm-forming pathogens commonly implicated in PJI. The organisms used for these experiments were Staphylococcus aureus and Pseudomonas aeruginosa. Biofilms were grown on stainless steel rings or washers, to model the surface of implanted prosthetics. P. aeruginosa was grown statically in MH2 media at 37°C for 48 hours. S. aureus was grown statically in Tryptic Soy Broth media supplemented with 0.5% glucose and 3.0% NaCl at 37°C for 48 hours. Soaking the stainless steel ring/washer in a 20% Human Plasma solution overnight at 4°C greatly enhanced S. aureus biofilm formation. AMF continuous dosing was performed at 20 watts, up to 15 minutes. AMF intermittent dosing was performed using 1 second duration, 670 watt pulses every 10 minutes, up to 6 hours. The results indicated that S. aureus biofilms were eradicated more effectively than P. aeruginosa biofilms when treated with intermittent AMF exposure. Specifically, there was a 2.6-log reduction in S. aureus biofilm CFU after 30 minutes of AMF exposure, with CFUs reaching the limit of detection after 3 hours. Corresponding studies in P. aeruginosa showed a 1.3-log reduction in biofilm CFU after 30 minutes of AMF exposure, with CFUs not reaching the limit of detection after 6 hours. In an ongoing study, ciprofloxacin was administered alongside AMF exposure to investigate any potential synergistic effects on P. aeruginosa biofilm eradication. While the data produced this summer was exclusively in vitro, the results give insight on how AMF might be applied in the clinical treatment of PJI. The observed cytotoxicity combined with the non-invasive nature of AMF suggest significant promise for a much more desired method of PJI treatment for common pathogens.Item Grapes of wrath: staphylococcal problems for the 1980's(1982-07-08) Munford, Robert S.Item Systems Biology of Staphylococcus Aureus Infection Ex Vivo and in Vitro(2012-07-09) Banchereau, Romain; Ramilo, OctavioStaphylococcus aureus has emerged as one of the most common community-acquired bacterial infections, with significant morbidity and mortality. Emergence of multidrug resistant strains worldwide, combined with limited treatment options demand novel approaches to further elucidate host-pathogen interactions, and especially host responses to infection. To this end, we leveraged systems biology approaches to better characterize the status of the host immune system during S. aureus infection ex vivo and in vitro. The transcriptional profiles of PBMC and whole blood from patients with community-acquired S. aureus infection were characterized by microarray analysis, and leukocyte population frequencies were measured by polychromatic flow cytometry. To refine our understanding of inflammatory networks involved, an in vitro system of antigen-presenting cell stimulation with various pathogens, including S. aureus as well as other bacteria and viruses, and their components, was used to identify early inflammatory programs induced in innate immune cells. To reduce the dimension and complexity of the data generated, we developed modular frameworks to analyze and interpret the fingerprints obtained from both the ex vivo and in vitro studies. // Overall, the blood transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis transcriptional programs, and under-expression of adaptive immunity programs. Flow cytometry and standard cell blood count (CBC) revealed an increase in absolute numbers of circulating monocytes, neutrophils and antigen-presenting cells, including dendritic cells and B cells, combined with a decrease in central memory T cells. To identify transcriptional correlates of clinical heterogeneity, we obtained individual fingerprints and derived the molecular distance to health, a numerical score of transcriptional perturbation for each patient. Patient-by-patient analysis without a priori knowledge of clinical diagnoses identified four major transcriptional clusters based on inflammation, erythropoiesis and interferon-induced profiles. Clinical presentation, bacterial dissemination and time between hospitalization and blood sampling were identified as major factors influencing the signature. The framework obtained from in vitro stimulation of monocyte-derived DC helped us refine the characterization of inflammatory programs activated during S. aureus infection. In addition to inflammatory antibacterial programs, S. aureus induced a subset of interferon response modules, also observed in viral infections and autoimmunity, as well as a specific set of modules linked to cell compartmentalization and lipid biosynthesis. Systems biology approaches provide a global and comprehensive assessment of host responses to acute bacterial infections, bringing a new understanding of disease pathogenesis and underlying patient heterogeneity.Item [UT Southwestern Medical Center News](2009-07-14) Shear, Kristen Holland