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Investigating Iron Transport and Utilization Features of Acinetobacter baumannii

Zimbler, Daniel Lawrence
http://rave.ohiolink.edu/etdc/view?acc_num=miami1364395692

Abstract Details

2013, Doctor of Philosophy, Miami University, Microbiology.
Acinetobacter baumannii is an important opportunistic human pathogen that causes severe nosocomial infections. The bacterium must overcome iron starvation and oxidative stress conditions imposed by the host in order to propagate and cause disease. This work further investigates the transport and utilization of iron by A. baumannii, and their involvement in virulence. The transport of iron is an active process and requires energy; A. baumannii ATCC 19606T contains and expresses three gene loci encoding functions in the TonB energy-transducing complex to provide the energy needed for iron transport. Transformation of Escherichia coli KP1344 with plasmids harboring the TonB components of these A. baumannii TonB systems promoted cell growth under iron-chelated conditions, which shows that these systems provide the necessary energy needed for iron acquisition. Inactivation of tonB1 and tonB2 in A. baumannii resulted in growth restriction under iron-chelation, indicating these genes are involved in iron transport. The Galleria mellonella infection model showed that TonB1 and TonB2 are involved, but are not essential for bacterial virulence, indicating A. baumannii carries redundant functional TonBs. Furthermore, TonB2 plays an additional role in the interaction with A549 human alveolar cells. Inactivation of dppA1A2 and dppBC, components of an inner membrane ABC transporter, did not affect growth under iron-chelation, suggesting alternative transport functions. However, inactivation of cirA, which codes for an iron-regulated outer membrane receptor resulted in reduced growth under iron-chelated conditions, indicating CirA has a role in iron transport. Furthermore, A. baumannii expresses hemin utilization functions independent of production and transport of acinetobactin-siderophore. Following transport, iron must be integrated into the intracellular iron pool. NfuA, a [Fe-S] cluster carrier protein was found to be involved in the ability of cells to respond to iron-limitation and oxidative stress, and is also needed for successful virulence in G. mellonella and within A549 cells. NfuA could be used for the maturation of intracellular [Fe-S] cluster containing proteins needed for the response to stresses encountered in the host. Taken together, the results here demonstrate that A. baumannii has implemented multiple mechanisms for the uptake and utilization of iron to ensure survival and propagation within the human host.
Luis Actis, PhD (Advisor)
Kelly Abshire, PhD (Committee Member)
Rachael Morgan-Kiss, PhD (Committee Member)
Gary Janssen, PhD (Committee Member)
David Tierney, PhD (Committee Member)
180 p.
Microbiology
Acinetobacter baumannii; Iron Acquisition; Iron-Sulfur Cluster; Iron Regulation

Recommended Citations

Citations

  • Zimbler, D. L. (2013). Investigating Iron Transport and Utilization Features of Acinetobacter baumannii [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1364395692

    APA Style (7th edition)

  • Zimbler, Daniel. Investigating Iron Transport and Utilization Features of Acinetobacter baumannii . 2013. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1364395692.

    MLA Style (8th edition)

  • Zimbler, Daniel. "Investigating Iron Transport and Utilization Features of Acinetobacter baumannii ." Doctoral dissertation, Miami University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=miami1364395692

    Chicago Manual of Style (17th edition)

miami1364395692
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© 2013, all rights reserved.
This open access ETD is published by Miami University and OhioLINK.