Acinetobacter baumannii is an emerging pathogen responsible for a significant percentage of nosocomial infections. It has also been problematic for the military in Iraq and Afghanistan, where it is the cause of softtissue infections associated with war-related trauma. Two properties of A. baumannii Xhaf contribute to its persistence as a pathogen are its propensity to accumulate drug resistance genes and a striking ability to tolerate biocides and desiccation. This project will use RNA-seq analysis to identify and define the functions of sRNA regulators (sRNAs) whose expression is associated with seven clinically relevant resistance traits of A. baumannii. These include resistance to four antibiotics, two biocides and desiccation. sRNAs are expressed in response to specific environmental signals, they are synthesized rapidly and they act quickly to control gene expression at the translational level. We hypothesize that sRNAs help A. baumannii io cope with cell envelope and metabolic stresses associated with antibiotic, biocide and desiccation exposure. Our results will open avenues for the development of new lines of defense against Acinetobacter infections.

Public Health Relevance

Acinetobacter baumannii causes infections in hospitalized patients. It is a problem to treat these infections because this microbe is resistant to multiple antibiotics. This project seeks to better understand why A. baumannii is so resistant to antibiotics.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-FDS-M)
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University of Washington
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Karalewitz, Andrew P-A; Miller, Samuel I (2018) Multidrug-Resistant Acinetobacter baumannii Chloramphenicol Resistance Requires an Inner Membrane Permease. Antimicrob Agents Chemother 62:
Chavez, Juan D; Lee, Chi Fung; Caudal, Arianne et al. (2018) Chemical Crosslinking Mass Spectrometry Analysis of Protein Conformations and Supercomplexes in Heart Tissue. Cell Syst 6:136-141.e5
Vreven, Thom; Schweppe, Devin K; Chavez, Juan D et al. (2018) Integrating Cross-Linking Experiments with Ab Initio Protein-Protein Docking. J Mol Biol 430:1814-1828
Zhong, Xuefei; Navare, Arti T; Chavez, Juan D et al. (2017) Large-Scale and Targeted Quantitative Cross-Linking MS Using Isotope-Labeled Protein Interaction Reporter (PIR) Cross-Linkers. J Proteome Res 16:720-727
Gallagher, Larry A; Lee, Samuel A; Manoil, Colin (2017) Importance of Core Genome Functions for an Extreme Antibiotic Resistance Trait. MBio 8:
Schweppe, Devin K; Chavez, Juan D; Lee, Chi Fung et al. (2017) Mitochondrial protein interactome elucidated by chemical cross-linking mass spectrometry. Proc Natl Acad Sci U S A 114:1732-1737
Miller, Samuel I (2016) Antibiotic Resistance and Regulation of the Gram-Negative Bacterial Outer Membrane Barrier by Host Innate Immune Molecules. MBio 7:
Baric, Ralph S; Crosson, Sean; Damania, Blossom et al. (2016) Next-Generation High-Throughput Functional Annotation of Microbial Genomes. MBio 7:
Chavez, Juan D; Schweppe, Devin K; Eng, Jimmy K et al. (2016) In Vivo Conformational Dynamics of Hsp90 and Its Interactors. Cell Chem Biol 23:716-26
Schweppe, Devin K; Chavez, Juan D; Navare, Arti T et al. (2016) Spectral Library Searching To Identify Cross-Linked Peptides. J Proteome Res 15:1725-31

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