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Light sensing in a human pathogen: genetic, biochemical, functional and proteomics analyses of blue light regulation in Acinetobacter baumannii

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2019, Doctor of Philosophy, Miami University, Microbiology.
Acinetobacter baumannii is a prevalent human pathogen commonly associated with severe nosocomial infections such as ventilator-associated pneumonia and wound infections in immunocompromised individuals. This pathogen is a global concern due to its ability to acquire resistance to antimicrobials and persist within the hospital environment for weeks under different pressures such as nutrient limitation and desiccation. The capacity of A. baumannii to survive in different niches, including in and on human hosts or abiotic environments within clinical settings suggests that this pathogen senses and responds to its surroundings to modulate its physiology to survive. Recently, it has been reported that A. baumannii senses and responds to blue light through the photoreceptor protein BlsA, with both factors playing significant roles in the regulation of surface motility, biofilm formation, metabolism and antibiotic resistance responses. The work presented here shows that the interaction of the BlsA N-terminal region with flavin chromophores determines light sensory functions and protein stability, while the C-terminal region could play critical photocycling and downstream regulatory functions. This work also demonstrates that the ability of A. baumannii to differentially display surface motility and biofilm formation on plastic at 24°C depends on the active expression of the PrpABCD type I pilus assembly system. Unexpectedly, analysis of a PrpA deficient mutant resulted in the detection of light regulated motility responses by bacteria cultured at 37°C, a condition that impairs BlsA production and its sensory functions. These unexpected observations suggest that A. baumannii senses and responds to illumination when incubated at 24°C and 37°C using different light sensing and regulatory systems. The application of a shotgun proteomics approach not only confirmed the predicted light-mediated BlsA-dependent differential expression of proteins at 24°C, but also showed that light regulates protein expression by bacterial cells cultured at 37°C by uncharacterized sensory and regulatory mechanisms. Taken together, the observations made during this work demonstrate that light is a ubiquitous environmental signal that allows A. baumannii to sense and adapt to conditions this pathogen would encounter while interacting with the human host and the surrounding nosocomial environment where it is exposed to different illumination and temperature conditions.
Luis Actis, Dr. (Advisor)
169 p.

Recommended Citations

Citations

  • Wood, C. R. (2019). Light sensing in a human pathogen: genetic, biochemical, functional and proteomics analyses of blue light regulation in Acinetobacter baumannii [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1556139448394676

    APA Style (7th edition)

  • Wood, Cecily. Light sensing in a human pathogen: genetic, biochemical, functional and proteomics analyses of blue light regulation in Acinetobacter baumannii. 2019. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1556139448394676.

    MLA Style (8th edition)

  • Wood, Cecily. "Light sensing in a human pathogen: genetic, biochemical, functional and proteomics analyses of blue light regulation in Acinetobacter baumannii." Doctoral dissertation, Miami University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=miami1556139448394676

    Chicago Manual of Style (17th edition)