Acinetobacter baumannii causes severe infections mainly in hospitalized patients. Lately, it has become a concern among wounded soldiers returning from the Middle East, where it has emerged as a """"""""fresh superbug."""""""" While a large body of information exists on typing methods and the mechanisms this bacterium uses to acquire/transfer genetic traits involved in antibiotic resistance, very little is known on the molecular, genetic and biological bases of the diseases caused by this pathogen. A. baumannii expresses virulence determinants responsible for the pathogenesis of the severe infections it causes in humans. Among them must be iron acquisition functions that allow bacteria to prosper under the iron-limited conditions of vertebrate hosts. Our work and the limited information published by others showed that A. baumannii 19606 expresses the high-affinity acinetobactin-mediated iron acquisition system and heme uptake functions to grow in bacteriological media under iron-limiting conditions. Our hypothesis is that these iron acquisition functions play a role in the physiology and the virulence of this pathogen. However, some important aspects related to the acinetobactin biosynthesis and secretion processes have not been elucidated and nothing is known about heme uptake functions in this pathogen. Furthermore, the role of these iron acquisition functions have not been tested using a relevant animal model that reflects the infections it causes in humans. Therefore, the aims of this proposal are: 1) the characterization of the acinetobactin secretion process;2) the analysis of heme uptake and utilization functions;3) the study of a SecA auxiliary protein secretion function involved in iron acquisition;and 4) the study of the virulence role of the acinetobactin and heme transport with an animal model that mimics human respiratory infections. These studies should advance our understanding of the molecular and biological bases of bacterial iron acquisition functions, some of which are poorly characterized, and their role in the pathogenesis of respiratory infections in vertebrate hosts. Some of these studies, particularly those proposed in the last specific aim, should also give the bases for future work aimed at elucidating the effects of bacterial iron acquisition systems on the physiology of the vertebrate host using global approaches. The latter approaches should provide a more comprehensive appreciation of the host-pathogen interactions that result in severe infections in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI070174-04
Application #
7846121
Study Section
Special Emphasis Panel (ZRG1-IDM-H (02))
Program Officer
Korpela, Jukka K
Project Start
2007-05-15
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
4
Fiscal Year
2010
Total Cost
$275,818
Indirect Cost
Name
Miami University Oxford
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
041065129
City
Oxford
State
OH
Country
United States
Zip Code
45056
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Arivett, Brock A; Fiester, Steven E; Ohneck, Emily J et al. (2015) Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes. Antimicrob Agents Chemother 59:7657-65
Naka, Hiroaki; Liu, Moqing; Actis, Luis A et al. (2013) Plasmid- and chromosome-encoded siderophore anguibactin systems found in marine vibrios: biosynthesis, transport and evolution. Biometals 26:537-47
Naka, Hiroaki; Actis, Luis A; Crosa, Jorge H (2013) The anguibactin biosynthesis and transport genes are encoded in the chromosome of Vibrio harveyi: a possible evolutionary origin for the pJM1 plasmid-encoded system of Vibrio anguillarum? Microbiologyopen 2:182-94
Zimbler, Daniel L; Arivett, Brock A; Beckett, Amber C et al. (2013) Functional features of TonB energy transduction systems of Acinetobacter baumannii. Infect Immun 81:3382-94
Fiester, Steven E; Actis, Luis A (2013) Stress responses in the opportunistic pathogen Acinetobacter baumannii. Future Microbiol 8:353-65
McConnell, Michael J; Actis, Luis; Pachon, Jeronimo (2013) Acinetobacter baumannii: human infections, factors contributing to pathogenesis and animal models. FEMS Microbiol Rev 37:130-55
Zimbler, Daniel L; Park, Thomas M; Arivett, Brock A et al. (2012) Stress response and virulence functions of the Acinetobacter baumannii NfuA Fe-S scaffold protein. J Bacteriol 194:2884-93
Penwell, William F; Arivett, Brock A; Actis, Luis A (2012) The Acinetobacter baumannii entA gene located outside the acinetobactin cluster is critical for siderophore production, iron acquisition and virulence. PLoS One 7:e36493
Nwugo, Chika C; Arivett, Brock A; Zimbler, Daniel L et al. (2012) Effect of ethanol on differential protein production and expression of potential virulence functions in the opportunistic pathogen Acinetobacter baumannii. PLoS One 7:e51936

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