Defining the regulatory control of desiccation tolerance in Acinetobacter baumannii

About This Grant

PROJECT SUMMARY: The ability to tolerate the complete loss of water is a rare but conserved trait observed across the diversity of life, including in many bacterial species. While desiccation is a common stress experienced by bacteria that primarily inhabit the natural environment, there are rare examples of host-associated bacteria that can tolerate extended periods of water loss. Acinetobacter baumannii is an emerging opportunistic bacterial pathogen that frequently colonizes mammalian hosts after contact with contaminated surfaces. The long-term persistence of A. baumannii on abiotic surfaces is well-documented and has been attributed to the extreme desiccation tolerance of this organism. Moreover, the ability of A. baumannii to readily transition between environmental and host-associated niches implies the evolution of sophisticated regulatory mechanisms that sense and transduce environmental stimuli, including water loss. However, the precise regulatory mechanisms A. baumannii employs to sense and respond to desiccation stress are not well understand. Previously, we uncovered two central regulatory proteins that interface to control desiccation tolerance in A. baumannii, the two-component transcriptional regulator BfmR, and the conserved protease Lon. We discovered that the regulatory processes controlled by these proteins are tightly linked, suggesting a mechanism whereby A. baumannii coordinates the regulated turnover of protein content with a global transcriptional response as a mechanism to program its long- term survival on abiotic surfaces. Over the next five years, we build on these recent discoveries to further delineate the precise regulatory networks and signal transduction pathways controlled by Lon and BfmR to facilitate adaptation to water loss. First, we will explore how regulated turnover of protein cargo by a newly discovered adaptor of Lon protease influences adaptation to desiccation. Second, we will elucidate the signal transduction mechanisms governing transcriptional control of desiccation tolerance by the BfmRS two- component system. Finally, we will define the mechanisms by which transcriptional and post-translational regulatory processes crosstalk to control desiccation tolerance in this organism. Together, this work will reveal novel factors mediating the extreme desiccation tolerance of A. baumannii and will create a framework for better understanding how bacteria induce multi-faceted regulatory processes to transition between host and environmental reservoirs.