Grant: Discovery Grants Program - Individual
University of Ontario Institute of Technology
$27,000.00
Characterization of RND efflux pumps of acinetobacter baumannii
FY 2012-13
Summary
Acinetobacter baumannii is a rod-shaped Gram-negative bacterium that commonly inhabits soil. A. baumannii is highly resistant to various antimicrobials, and multidrug clinical isolates have been isolated all over the world including in Canada. Our hypothesis is that efflux pumps belonging to the Resistance-Nodulation-cell Division (RND) family aid in the survival of A. baumannii in the presence of harmful compounds (including antimicrobials, heavy metals, detergents, and dyes), and that characterization of these efflux pumps will contribute to an understanding of the survival mechanisms employed by this organism. Using powerful molecular and genetic tools, this program will characterize three RND complex-encoding operons,
adeGH, adeMNO, and adeTUVW, from A. baumannii. Gene knock-outs of RND pumps will be created and resistance profiles of knock-outs will be compared to the parent strains. The regulatory aspects of RND pumps in this organism will also be investigated by a molecular approach whereby state-of-the-art genetic tools will be employed to construct strains that will constitutely express A. baumannii pumps in single copy. To this end, gene knock-out strategies will be used to create efflux-sensitized strains with deletions in, not only the aforementioned putative RND operons, but also in the previously-identified A. baumannii efflux pumps, AdeABC, AdeDE, and AdeIJK. In the long term, knock-out strains constructed in this study will be used to express individual A. baumannii RND pumps in single copy and thus will serve as a valuable tool for Efflux Pump Inhibitor (EPI) discovery. The proposed research will not only lead to a better understanding of mechanisms of survival of this organism in hostile conditions, but will also ultimately prove useful in identification of more effective therapeutic drugs to eradicate infections caused by A. baumannii. In addition, this program will lead to the development of novel genetic tools for A. baumannii, that will be invaluable for other researchers interested in this organism.
Program
Discovery Grants Program - Individual
Location
Ontario, Canada
Recipient Type
Academia
Type
Grant
Source
NSERC's Awards Data
As published
Application id
355806-2010
Name nom
Kumar, Ayush
Department département
Health Sciences, Faculty of
Organization id
19222
Institution établissement
University of Ontario Institute of Technology
Province en
Ontario
Province fr
Ontario
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2012
Competition year année de concours
2010
Award amount
27000
Program id
RGPIN
Program name en
Discovery Grants Program - Individual
Program name fr
Programme de subventions à la découverte - individuelles
Group en
Discovery grants programs
Group fr
Programmes de subventions à la découverte
Committee code
1501
Committee name en
Genes, Cells and Molecules
Committee name fr
Gènes, cellules et molécules
Area of application code
1201
Area of application group en
Advancement of knowledge
Area of application group fr
Avancement des connaissances
Area of application en
Life sciences (including biotechnology)
Area of application fr
Sciences de la vie (y compris biotechnologie)
Research subject code
5201
Research subject group en
Microbiology
Research subject group fr
Microbiologie
Research subject en
Bacteriology
Research subject fr
Bactériologie
Partie
3
Nb partie
5
Application title
Characterization of RND efflux pumps of acinetobacter baumannii
Keyword
NSERC
Application summary
Acinetobacter baumannii is a rod-shaped Gram-negative bacterium that commonly inhabits soil. A. baumannii is highly resistant to various antimicrobials, and multidrug clinical isolates have been isolated all over the world including in Canada. Our hypothesis is that efflux pumps belonging to the Resistance-Nodulation-cell Division (RND) family aid in the survival of A. baumannii in the presence of harmful compounds (including antimicrobials, heavy metals, detergents, and dyes), and that characterization of these efflux pumps will contribute to an understanding of the survival mechanisms employed by this organism. Using powerful molecular and genetic tools, this program will characterize three RND complex-encoding operons,
adeGH, adeMNO, and adeTUVW, from A. baumannii. Gene knock-outs of RND pumps will be created and resistance profiles of knock-outs will be compared to the parent strains. The regulatory aspects of RND pumps in this organism will also be investigated by a molecular approach whereby state-of-the-art genetic tools will be employed to construct strains that will constitutely express A. baumannii pumps in single copy. To this end, gene knock-out strategies will be used to create efflux-sensitized strains with deletions in, not only the aforementioned putative RND operons, but also in the previously-identified A. baumannii efflux pumps, AdeABC, AdeDE, and AdeIJK. In the long term, knock-out strains constructed in this study will be used to express individual A. baumannii RND pumps in single copy and thus will serve as a valuable tool for Efflux Pump Inhibitor (EPI) discovery. The proposed research will not only lead to a better understanding of mechanisms of survival of this organism in hostile conditions, but will also ultimately prove useful in identification of more effective therapeutic drugs to eradicate infections caused by A. baumannii. In addition, this program will lead to the development of novel genetic tools for A. baumannii, that will be invaluable for other researchers interested in this organism.
