Acinetobacter baumannii gene regulation in response to illumination

Actis, Luis

Abstract

Some bacteria, such as Acinetobacter baumannii, cause human infections but spend portions of their life cycles both inside and outside medical settings. The understanding of how these bacteria adapt to and persist in significantly different environments is very limited. The elucidation of the environmental factors and the cellular and molecular mechanisms that enable bacteria to transition between environmental and nosocomial lifestyles is critical for understanding not only basic cellular processes that play a role in this transition, but also the ecology of bacteria that cause relevant human infections worldwide. A. baumannii is known for its capacity to resist antimicrobial agents and host defenses, endure and prosper under nutrient limitation in different ecological niches, attach to and form biofilms on abiotic and biotic surfacs, resist desiccation, and persist in water, soil, vertebrate and invertebrate animals and different food sources. Thus, we believe that this bacterium recognizes and responds to a wide range of extracellular signals to persist under different conditions and environments. Accordingly, we made the unexpected and novel observation that, although non- photosynthetic, A. baumannii senses and responds to light by differentially expressing biofilm formation and motility activities through a process mediated by BlsA, a short blue-light sensing using flavin (BLUF)-domain- containing photoreceptor protein, by unknown mechanisms. Based on these observations, our central hypothesis is that light provides, through a BlsA-mediated process, a spatial localization signal, rather than a global stress signal, which allows A. baumannii to choose different lifestyle needed to persist in distinct ecological niches under different environmental conditions. This hypothesis will be tested by pursuing three specific aims: 1) Identify structure-function relationships critical for BlsA light-sensing and regulatory functions using molecular genetics, biophysical/biochemical studies and biological assays; 2) Determine the extent and components of the light stimulon and BlsA regulon using transcriptomics and protein studies; and 3) Characterize the light-regulated LrpABCD chaperone/usher pili system using molecular genetics, biochemical assays, functional tests and electron microscopy methods. It is anticipated that this work will provide novel insights into the mechanisms by which bacteria sense and respond to a ubiquitous cue - light - that signals their location, rather than only causing a global stress reaction, and triggers responses needed to interact with abiotic and biotic elements found in different environments using A. baumannii as a working model. These studies are also significant since they have a positive translational impact by opening new avenues to better understand the ecology of A. baumannii in medical settings and the natural environment, which could serve as its reservoir, as well as to better understand short photoreceptors such as BlsA, which could be active in more than 60 non-photosynthetic unrelated bacteria.

Public Health Relevance

The proposed research plan should provide a better understanding of how light, as an environmental signal, affects the capacity of bacteria to persist in different environments. This fundamental knowledge, which will be obtained using the non-photosynthetic bacterium Acinetobacter baumannii as a working model, will provide novel insights into poorly characterized ecological and bacterial factors relevant to human health.