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Dr K Rajakumar
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
This PhD project exploits comparative genomics, conventional genetics, diverse molecular approaches, and models of adaptation and infection to identify, capture and functionally characterize genomic islands (GIs) present in Klebsiella pneumoniae or Acinetobacter baumannii. Both of these bacterial pathogens remain poorly studied, and this project will test the hypothesis that large-scale genomic differences account for major disease-causing and phenotypic traits. High-throughput genome sequencing and microarray-based comparative genomics have revealed that many bacterial species exhibit an extremely plastic genome. Growing data supports the hypothesis that phenotypic traits of individual bacterial strains are largely governed by the precise complement of genes and/or GIs borne by a particular strain. GIs that encode varying complements of strain-specific genes punctuate the chromosomal backbones of many bacteria. GIs comprise a wide spectrum of elements ranging from intact and degenerate prophages, chromosomally captured plasmids, complex hybrid entities, archetypal integrative elements to simple single-gene islets. Pathogenicity islands (PAIs), the virulence-associated subset of GIs, encode determinants such as invasins, toxins, adhesins, autotransporters, fimbrial appendages and multi-component secretory 'syringes'. PAIs and resistance islands have now been identified in many bacterial species and are undoubtedly major players behind the success of bacterial pathogens.
Specific aims: (1) To define the genomic island content of bacterial isolates from patients with varied infections; (2) To engineer mutants lacking up to four defined islands and/or target genes; (3)To examine in detail the resultant phenotype and virulence properties of these strains.
This project will play a major role in elucidating the role of GIs in Klebsiella or Acinetobacter and will lead in time to novel strategies for the prevention, diagnosis and treatment of infections. PhD opportunities in bacteriophage genetics/biology, bioinformatics, molecular diagnostics and clinical microbiology are also offered; direct enquiries welcome (Email: [Email Address Removed]).
We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.
Specific aims: (1) To define the genomic island content of bacterial isolates from patients with varied infections; (2) To engineer mutants lacking up to four defined islands and/or target genes; (3)To examine in detail the resultant phenotype and virulence properties of these strains.
This project will play a major role in elucidating the role of GIs in Klebsiella or Acinetobacter and will lead in time to novel strategies for the prevention, diagnosis and treatment of infections. PhD opportunities in bacteriophage genetics/biology, bioinformatics, molecular diagnostics and clinical microbiology are also offered; direct enquiries welcome (Email: [Email Address Removed]).
We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.
References
RAJAKUMAR ET AL
Bi et al. 2013. SecReT4: a web-based bacterial type IV secretion system resource. Nucleic Acids Res 41(D1):D660-5.
Bi et al. 2012. ICEberg: a web-based resource for integrative and conjugative elements found in Bacteria. Nucleic Acids Res 40(Database issue):D621-6.
van Aartsen et al. 2012. Characterization of a novel chaperone/usher fimbrial operon present on KpGI-5, a methionine tRNA gene-associated genomic island in Klebsiella pneumoniae. BMC Microbiol 12:59.
Kochar et al. 2012. Deletion of TnAbaR23 results in both expected and unexpected antibiogram changes in a multi-drug resistant Acinetobacter baumannii strain. Antimicrob Agents Chemother 56:1845-53.
Harrison et al. 2010. The pathogenicity islands PAPI-1 and PAPI-2 contribute individually and synergistically to virulence of Pseudomonas aeruginosa strain PA14. Infect Immun 78:1437-46.
Shaikh et al. 2008. ATPase genes of diverse multidrug-resistant Acinetobacter baumannii isolates frequently harbour integrated DNA. J Antimicrob Chemother 63: 260-4.
Ou et al. 2007. MobilomeFINDER: web-based tools for in silico and experimental discovery of bacterial genomic islands. Nucleic Acids Res 35:W97-W104.
He et al. 2007. Analysis of a genomic island housing genes for DNA S-modification system in Streptomyces lividans 66 and its counterparts in other distantly related bacteria. Mol Microbiol 65:1034-48.
Luck et al. 2001. Ferric dicitrate transport system (Fec) of Shigella flexneri 2a YSH6000 is encoded on a novel pathogenicity island carrying multiple antibiotic resistance genes. Infect Immun 69:6012-21.
Al-Hasani et al. 2000. The sigA gene which is borne on the she pathogenicity island of Shigella flexneri 2a encodes an exported cytopathic protease involved in intestinal fluid accumulation. Infect Immun 68:2457-63.
Rajakumar et al. 1997. Use of a novel approach, termed island probing, identifies the Shigella flexneri she pathogenicity island which encodes a homolog of the immunoglobulin A protease-like family of proteins. Infect Immun 65:4606-14.
PATHOGENICITY AND GENOMIC ISLAND REVIEWS
Dobrindt et al. 2004. Genomic islands in pathogenic and environmental microorganisms. Nat Rev Microbiol 2:414-24.
Gal-Mor and Finlay. 2006. Pathogenicity islands: a molecular toolbox for bacterial virulence. Cell Microbiol 8:1707-19.
Bi et al. 2013. SecReT4: a web-based bacterial type IV secretion system resource. Nucleic Acids Res 41(D1):D660-5.
Bi et al. 2012. ICEberg: a web-based resource for integrative and conjugative elements found in Bacteria. Nucleic Acids Res 40(Database issue):D621-6.
van Aartsen et al. 2012. Characterization of a novel chaperone/usher fimbrial operon present on KpGI-5, a methionine tRNA gene-associated genomic island in Klebsiella pneumoniae. BMC Microbiol 12:59.
Kochar et al. 2012. Deletion of TnAbaR23 results in both expected and unexpected antibiogram changes in a multi-drug resistant Acinetobacter baumannii strain. Antimicrob Agents Chemother 56:1845-53.
Harrison et al. 2010. The pathogenicity islands PAPI-1 and PAPI-2 contribute individually and synergistically to virulence of Pseudomonas aeruginosa strain PA14. Infect Immun 78:1437-46.
Shaikh et al. 2008. ATPase genes of diverse multidrug-resistant Acinetobacter baumannii isolates frequently harbour integrated DNA. J Antimicrob Chemother 63: 260-4.
Ou et al. 2007. MobilomeFINDER: web-based tools for in silico and experimental discovery of bacterial genomic islands. Nucleic Acids Res 35:W97-W104.
He et al. 2007. Analysis of a genomic island housing genes for DNA S-modification system in Streptomyces lividans 66 and its counterparts in other distantly related bacteria. Mol Microbiol 65:1034-48.
Luck et al. 2001. Ferric dicitrate transport system (Fec) of Shigella flexneri 2a YSH6000 is encoded on a novel pathogenicity island carrying multiple antibiotic resistance genes. Infect Immun 69:6012-21.
Al-Hasani et al. 2000. The sigA gene which is borne on the she pathogenicity island of Shigella flexneri 2a encodes an exported cytopathic protease involved in intestinal fluid accumulation. Infect Immun 68:2457-63.
Rajakumar et al. 1997. Use of a novel approach, termed island probing, identifies the Shigella flexneri she pathogenicity island which encodes a homolog of the immunoglobulin A protease-like family of proteins. Infect Immun 65:4606-14.
PATHOGENICITY AND GENOMIC ISLAND REVIEWS
Dobrindt et al. 2004. Genomic islands in pathogenic and environmental microorganisms. Nat Rev Microbiol 2:414-24.
Gal-Mor and Finlay. 2006. Pathogenicity islands: a molecular toolbox for bacterial virulence. Cell Microbiol 8:1707-19.
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