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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI107775-01
Application #
8597719
Study Section
Special Emphasis Panel (ZAI1-FDS-M (M1))
Project Start
2013-06-24
Project End
2018-05-31
Budget Start
2013-06-24
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$350,459
Indirect Cost
$126,684
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Schweppe, Devin K; Chavez, Juan D; Bruce, James E (2016) XLmap: an R package to visualize and score protein structure models based on sites of protein cross-linking. Bioinformatics 32:306-8
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
Baric, Ralph S; Crosson, Sean; Damania, Blossom et al. (2016) Next-Generation High-Throughput Functional Annotation of Microbial Genomes. MBio 7:
Schweppe, Devin K; Zheng, Chunxiang; Chavez, Juan D et al. (2016) XLinkDB 2.0: integrated, large-scale structural analysis of protein crosslinking data. Bioinformatics 32:2716-8
DeBlasio, Stacy L; Chavez, Juan D; Alexander, Mariko M et al. (2016) Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology. J Virol 90:1973-87
Wu, Xia; Chavez, Juan D; Schweppe, Devin K et al. (2016) In vivo protein interaction network analysis reveals porin-localized antibiotic inactivation in Acinetobacter baumannii strain AB5075. Nat Commun 7:13414
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
Miller, Samuel I (2016) Antibiotic Resistance and Regulation of the Gram-Negative Bacterial Outer Membrane Barrier by Host Innate Immune Molecules. MBio 7:
Gallagher, Larry A; Ramage, Elizabeth; Weiss, Eli J et al. (2015) Resources for Genetic and Genomic Analysis of Emerging Pathogen Acinetobacter baumannii. J Bacteriol 197:2027-35
Gebhardt, Michael J; Gallagher, Larry A; Jacobson, Rachael K et al. (2015) Joint Transcriptional Control of Virulence and Resistance to Antibiotic and Environmental Stress in Acinetobacter baumannii. MBio 6:e01660-15

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