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- All Subjects: Microbiology
- Creators: Barrila, Jennifer
- Status: Published
One of the identified health risk areas for human spaceflight is infectious disease, particularly involving environmental microorganisms already found on the International Space Station (ISS). In particular, bacteria belonging to the Burkholderia cepacia complex (Bcc) which can cause human disease in those who are immunocompromised, have been identified in the ISS water supply. This present study characterized the effect of spaceflight analog culture conditions on Bcc to certain physiological stresses (acid and thermal as well as intracellular survival in U927 human macrophage cells). The NASA-designed Rotating Wall Vessel (RWV) bioreactor was used as the spaceflight analogue culture system in these studies to grow Bcc bacterial cells under Low Shear Modeled Microgravity (LSMMG) conditions. Results show that LSMMG culture increased the resistance of Bcc to both acid and thermal stressors, but did not alter phagocytic uptake in 2-D monolayers of human monocytes.
Collectively, this work represents the first characterization of in vivo virulence and in vitro pathogenesis properties of D23580, the latter using advanced human surrogate models that mimic key aspects of the parental tissue. Results from these studies highlight the importance of studying infectious diseases using an integrated approach that combines actions of biological and physical networks that mimic the host-pathogen microenvironment and regulate pathogen responses.
In this dissertation, I developed a nonculture-based AST using an imaging and cell tracking technology. I track individual Escherichia coli O157:H7 (E. coli O157:H7) Uropathogenic Escherichia Coli (UPEC) cells, widely implicated in food-poisoning outbreaks and urinary tract infections respectively. Cells tethered to a surface are tracked on the nanometer scale, and phenotypic motion is correlated with bacterial metabolism. Antibiotic action significantly slows down motion of tethered bacterial cells, which is used to perform antibiotic susceptibility testing. Using this technology, the clinical minimum bactericidal concentration of an antibiotic against UPEC pathogens was calculated within 2 hours directly in urine samples as compared to 3 days using current gold standard tools.
Such technologies can make a tremendous impact to improve the efficacy and efficiency of infectious disease treatment. This has the potential to reduce the antibiotic mis-prescription steeply, which can drastically decrease the annual 2M+ hospitalizations and 23,000+ deaths caused due to antibiotic resistance bacteria along with saving billions of dollars to payers, patients, and hospitals.
phosphate or magnesium to the culture medium abrogated the fluid shear-related differences observed for A130 in LB medium for the acid or oxidative stress responses, respectively. Collectively, these findings indicate that like other Salmonella strains assessed thus far by our team, A130 responds to differences in physiological fluid shear, and that ion concentrations can modulate those responses.