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The Molecular Microbiology of Enterobacterial Quorum Sensing, Virulence, Antibiotics, Protein Secretion, and Bacteriophage-Host Interactions

  • Full or part time
    Prof Salmond
  • Application Deadline
    Applications accepted all year round
  • Awaiting Funding Decision/Possible External Funding
    Awaiting Funding Decision/Possible External Funding

Project Description

We work on enterobacterial pathogens of plants and animals, namely Erwinia, Serratia and Citrobacter and we are investigating their molecular biology from several fronts: genetical, biochemical and physiological. We are studying the role of quorum sensing (QS) in virulence in these bacterial pathogens and looking at the signal transduction routes and the nature of the corresponding target genes and processes controlled by QS. One such process is the regulation of carbapenem antibiotic production in Erwinia and Serratia and the regulation and biosynthesis of the antimicrobial, immunosuppressant and anti-cancer agent, prodigiosin, in Serratia species. In addition to these bacterial pathogens, QS also plays roles in the regulation of virulence factors in the murine pathogen, Citrobacter rodentium and we are dissecting this process. QS also affects production of novel and potentially biotechnologically useful antifungal molecules by rhizosphere bacteria which we have made genetically amenable. The products of the QS-regulated genes in Erwinia, Serratia and Citrobacter are being investigated via advanced proteomics and by microarray technologies and we have exploited such methods in the study of the Erwinia secretome. In addition to the role of QS in these enterobacterial pathogens, we are investigating the roles of new phages that infect these pathogens, both in terms of natural phage conversion but also by exploiting them for functional genomics techniques. Some of these bacterial pathogens have evolved impressive adaptive responses to phage infection (abortive infection systems). We have interests in the role of abortive infection mechanisms in these phage-host interactions from evolutionary, physiological, structural and ecological perspectives. Our research takes integrated approaches, including 'omic technologies (including deep sequencing) in the study of Erwinia, Serratia and Citrobacter. Diverse techniques are used in this lab, including bacterial genetics, genomics, secretion studies via advanced proteomics, cloning, protein expression, gene fusions, mRNA assays, assays of antibiotics and quorum sensing molecules and virulence assays. We also have growing interest in aspects of structural biology, through collaboration with X-ray crystallographers within the department.

Funding Notes

Open to students from all geographical locations, depending on funding. UK research council funding is only available to UK and EU students, by an active and highly competitive internal competition and review system.

References

Bell, K., et al (2004) Genome sequence of the enterobacterial phytopathogen, Erwinia carotovora subsp. atroseptica and characterisation of novel virulence factors. Proceedings of the National Academy of Sciences, USA, 101, 11105-11110.

Pemberton, C., et al (2005) Novel quorum sensing-regulated genes in Erwinia carotovora subspecies carotovora: identification of a fungal elicitor homologue in the soft rotting bacterium. Molecular Plant-Microbe Interactions, 18, 343-353

McGowan, S., et al (2005) Carbapenem antibiotic biosynthesis in Erwinia carotovora is regulated by multiple physiological and genetic factors modulating the quorum sensing-dependent pathway. Molecular Microbiology 55, 526-545

Coulthurst, S., et al (2005) Regulation and biosynthesis of carbapenem antibiotics in bacteria. Nature Reviews Microbiology 3:295-306

Williamson, N., et al (2005) Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel methyl-n-amyl-pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme and implications for undecylprodigiosin biosynthesis in Streptomyces. Molecular Microbiology 56, 971-989

Fineran, P et al (2005) Biosynthesis of tripyrrole and b-lactam secondary metabolites in Serratia: integration of the quorum sensing system with multiple new regulatory components in the control of prodigiosin and carbapenem antibiotic production. Molecular Microbiology 56, 1495-1517

Williamson, N., Fineran, P., Leeper, F. and Salmond, GPC (2006) The biosynthesis and regulation of bacterial prodiginines. Nature Reviews Microbiology (In press, December)

Liu, H, et al (2008) Quorum sensing coordinates brute force and stealth modes of infection in the plant pathogen Pectobacterium atrosepticum'. PloS – Pathogens 4, e1000093. doi:10.1371/journal.ppat.1000093

Coulthurst, SJ, et al (2008) DsbA plays a critical and multi-faceted role in the production of secreted virulence factors by the phytopathogen, Erwinia carotovora subsp. atroseptica. Journal of Biological Chemistry 283: 23739 – 23753

Welch, M. et al (2005) Structure-activity relationships of Erwinia carotovora quorum sensing signalling molecules. Bioorganic and Medicinal Chemistry Letters, 15/19, 4235-4238

Williamson, NR., et al (2008) Integrated regulation involving quorum sensing, a two-component system, a GGDEF/EAL domain protein and a post-transcriptional regulator controls swarming and RhlA-dependent surfactant biosynthesis in Serratia. Environmental Microbiology 10, 1202-1217

Fineran, P., et al (2009) The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. PNAS, USA (In Press)

Blower, T et al (2009) Mutagenesis and functional characterisation of the RNA and protein components of the toxIN abortive infection / toxin-antitoxin locus of Erwinia. Journal of Bacteriology (in Press)


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