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- Title
- EFFECT OF METABOLIC INHIBITORS ON GROWTH AND BIOFILM DEVELOPMENT OF ENTEROBACTER AEROGENES AND KLEBSIELLA PNEUMONIAE
- Creator
- Sanjana, Krithica
- Date
- 2017, 2017-05
- Description
-
Enterobacter aerogenes and Klebsiella pneumoniae are the leading cause of severe hospital-acquired infections across the globe, particularly...
Show moreEnterobacter aerogenes and Klebsiella pneumoniae are the leading cause of severe hospital-acquired infections across the globe, particularly in the US and Europe. These bacteria contribute heavily to the alarming threat of emergence of multiple drug resistant strains, enabling them to survive a wide spectrum of antibiotics. One of the key factors involved in drug resistance is the production of biofilms, a complex exopolysaccharide matrix that acts as a protective component and increase their resistance to external factors including antibiotics. In this study, we described that targeting the bacterial respiratory metabolism entirely disrupts pathways used for energy synthesis and substantially inhibits bacterial growth. Moreover, the metabolic inhibitors decreased the production of biofilms by these bacteria. Two key factors being the bacterial growth and biofilm development were analyzed in this research study. The data indicates that HQNO has the highest inhibition effect which targets essential enzyme complex Na+-NQR in bacterial growth as well as biofilm formation. Thus, the structure of HQNO can potentially be suited for new antibiotic development to combat the problem of multidrug resistant bacteria.
M.S. in Biology, May 2017
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- Title
- Characterization of the Pseudomonas aeruginosa NQR Complex, a Novel Form of Bacterial Proton Pump, and the Ubiquinone Binding Site
- Creator
- Raba, Daniel Alexander
- Date
- 2019
- Description
-
The proton/sodium pumping NADH:Ubiquinone oxidoreductase enzyme complex (NQR) plays a key role in the energy metabolism of a diverse range of...
Show moreThe proton/sodium pumping NADH:Ubiquinone oxidoreductase enzyme complex (NQR) plays a key role in the energy metabolism of a diverse range of bacteria, including pathogenic species such as Vibrio cholera, Pseudomonas aeruginosa, Chlamydia trachomatis, as well as others. Residing in the cytoplasmic membrane of these bacteria, the enzyme couples the transfer of electrons to the pumping of cations across the cell membrane. In all previously studied homologues, the enzyme generates a sodium gradient through its pumping activity that can be utilized by the cell to power essential homeostatic processes. Furthermore, the electrochemical gradient generated by this enzyme has been shown to regulate the production of virulent factors and the efficacy of antibiotic extrusion and elimination. Although certain homologues have been investigated, particularly that of V. cholerae (Vc-NQR), the NQR homologues belonging to important pathogenic species have not been well studied. In the research detailed in this thesis, the first characterization of the NQR of P. aeruginosa (Pa-NQR) is described which identified this homologue as a new form of bacterial proton pump, differentiating it from all other studied homologues of NQR. Additionally, as part of this study our research group characterized the mechanism of inhibition of Pa-NQR by the molecule HQNO which is produced by P. aeruginosa and is known to be a strong inhibitor of Vc-NQR. Our results show that Pa-NQR possesses resistance to inhibition by this molecule compared to Vc-NQR, pinpointing residue F155 of subunit D as being important to resistance and the type of inhibition to be partial-mixed. Moreover, in further developing the understanding of the NQR of V. cholerae, we investigated the binding site of ubiquinone, the final electron acceptor of NQR’s electron transfer process, determining residues P185, L190, and F193 to be important for maintaining the structural composition of the ubiquinone pocket, ensuring efficient substrate binding and catalysis.
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