Increasing rates of antibiotic resistant, hospital-acquired bacterial infections, and our diminishing antibiotic options, are undercutting all medical treatments that require hospital-based recovery. Understanding how bacteria persist and spread in hospitals is paramount to elevating the burden of antibiotic resistant hospital-associated bacterial infections. Acinetobacter baumannii is a hospital-associated pathogen of rapidly growing importance, and is a paradigm for endemic clinical contamination. Reoccurring hospital outbreaks of endemic A. baumannii strains are well documented, as are its colonization of a wide array of medical equipment and the difficulty of exterminating it from hospitals. A. baumannii's robust desiccation tolerance is a key characteristic exacerbating each of these problems, however scarce information is available describing the underlying mechanisms of desiccation-induced lethality and survival for A. baumannii or any bacterium. The overall objectives of this proposal are to characterize the role of oxidative stress and proteostasis components critical for desiccation tolerance.
The specific aims of this proposal are (1) to characterize the role and identify targets of oxidative stress during desiccation and (2) to characterize components of A. baumannii's protein chaperone network that promote desiccation survival. The completion of these aims will contribute to an essential body of knowledge to the persistence of bacteria in the clinical setting and provide a better understanding of the mechanisms by which A. baumannii survives for long periods of time in the desiccated state. This proposal represents a preventative approach to eradicating contamination and spread of pathogenic bacteria in hospitals and will offer a framework for future investigation of a critical, yet understudied, aspect of infectious disease control.
With rapidly shrinking antibiotic options, prevention is paramount in elevating the burden of hospital-acquired infections. The aim of this proposal is to characterize the mechanisms of persistence of desiccated bacteria in order to provide the basic science framework for future preventative infection strategies.
| Tucker, Ashley T; Leonard, Sean P; DuBois, Cory D et al. (2018) Discovery of Next-Generation Antimicrobials through Bacterial Self-Screening of Surface-Displayed Peptide Libraries. Cell 172:618-628.e13 |
| Boll, Joseph M; Tucker, Ashley T; Klein, Dustin R et al. (2015) Reinforcing Lipid A Acylation on the Cell Surface of Acinetobacter baumannii Promotes Cationic Antimicrobial Peptide Resistance and Desiccation Survival. MBio 6:e00478-15 |
