PN-II-RU-TE-2014-4-0604

Functional and pharmacological characterization of Na+/H+ antiport systems of Klebsiella pneumoniae

Romanian version ro


Contract: 68/01/10/2015
Duration: 24 months
Finance source: State budget, contracting authority: Romanian National Authority for Scientific Research and
Innovation, CNCS – UEFISCDI
Budget: 550000 RON
Project start: 01.10.2015
Project end: 30.09.2017

Summary

Regulation of intracellular Na+ concentration and pH is a prerequisite for the survival of any organism. The main effectors of this process are secondary active transport systems, the Na+/H+ antiporters or exchangers that exist in virtually all organisms. Understanding of Na+/H+ antiporters is crucial as they have been shown in humans to be involved in various pathologies, while in bacteria they can be essential for survival and virulence. Klebsiella pneumoniae is one pathogen that has, in recent years, become resistant to common antibiotic therapy and can cause infections with a high mortality rate in immunocompromised or debilitated patients. A better understanding of transporter systems in K. pneumoniae might thus allow for development of more effective treatment options. In the framework of our project, we plan to characterize the Na+/H+ transport systems of K. pneumoniae: KpNhaA1, KpNhaA2, KpNhaB and KpNhaP2. This will be done mainly by the use of solid-supported membrane-based electrophysiology in combination with fluorimetric techniques. Overall, our goal is to obtain a better understanding of Na+/H+ antiport in K. pneumoniae and determine kinetic parameters allowing us to model antiporter function under given environmental conditions. We will also test various inhibitors in order to determine potential means of inhibiting Na+/H+ antiport in K. pneumoniae.

Research team

Lecturer Dr. Octavian Călinescu - Project Director
Prof. Dr. Constanța Ganea - Senior Researcher
Conf. Dr. Adrian Iftime - Postdoctoral Researcher
Ioana Tofolean - PhD Student
Alexandru Filippi - PhD Student
Rodica Zaharia - Technical Assistant


Conference attendances

1. Călinescu, O., Fendler, K., “A Universal Transport Mechanism for Na+/H+ Exchangers”, International Workshop: Proton and Proton-coupled Transport, 27-29 mai 2016, Berlin, Germany.

2. Călinescu, O., Iftime, A., Ganea, C., Fendler, K., “Electrophysiological Investigation of Prokaryotic Na+/H+ Exchangers”, Conferința Națională de Biofizică, 2-4 iunie 2016, Cluj-Napoca, Romania, ISSN: 2248-0749.


Journal articles

1. Călinescu, O., Linder, M., Wöhlert, D., Yildiz, Ö., Kühlbrandt, W., Fendler, K., “Electrogenic Cation Binding in the Electroneutral Na+/H+ Antiporter of Pyrococcus abyssi”, J. Biol. Chem., 2016, DOI: 10.1074/jbc.M116.761080.


Prospective results


Scientific activity reports

Phase I (2015, english, pdf)

Phase II (2016, english, pdf)


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