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George Salmond

Molecular microbiology: bacterial quorum sensing, virulence, protein secretion, antibiotic regulation, gas vesicles and flotation, toxin-antitoxin systems and bacteriophage abortive infection

Our research involves multiple aspects of molecular microbiology including quorum sensing (QS), molecular pathogenesis in plant and animal pathogens, regulation and biosynthesis of antibiotics and other secondary metabolites, protein secretion systems, gas vesicles and flotation, bacteriophage exploitation, toxin-antitoxin systems and anti-viral abortive infection. We work on various Gram-negative enterobacteria, including the phytopathogen, Erwinia (Pectobacterium), Serratia species (which can be opportunistic human pathogens) Citrobacter rodentium (the murine pathogen) and a spectrum of phages infecting bacteria of fundamental, medical, agricultural or industrial biotechnology interest (including Pseudomonas and Streptomyces).

We are investigating the phenomenon of quorum sensing in which bacteria make small diffusible molecules (N-acyl homoserine lactones) as chemical communication signals reflecting cell population density status. The phenotypes regulated by quorum sensing include virulence, exoenzyme and antibiotic production, and gas vesicle organelle morphogenesis. We aim to understand molecular mechanisms involved in quorum sensing, and dissect their physiological role(s), evolution, and potential use in synthetic biology. We study the genetics and biochemistry of production of carbapenems, prodiginines and haterumalides/oocydins in enterobacteria such as  Erwinia (Pectobacterium), Dickeya, Serratia and other rhizosphere organisms. We use genetics, transcriptomics and proteomics to investigate the physiological impacts of environmental signaling in the regulation of virulence and antibiotic production in Erwinia and Serratia. We also investigate molecular processes involved in virulence factor secretion in Erwinia. We are exploiting new bacteriophages for the development of genetic tools in functional genomics. We are also studying phage abortive infection systems (with bifunctional toxin-antitoxin capacity) through which bacteria control the replication of their viral parasites. We are also investigating the morphogenesis of bacterial gas vesicles (flotation chambers) as intracellular organelles which develop in response to a quorum sensing morphogen and other environmental cues.

Lab members: Rita Monson, Miguel Angel Matilla Vazquez, Alison Rawlinson, Feng Rao, Chin Mei Lee, Xinzhe Fang, Josephine Hellberg

Key publications:

1. Short, F. et al (2013) Selectivity and self-assembly in the control of a bacterial toxin by an antitoxic noncoding RNA pseudoknot. PNAS, 110 (3) E241–E249. First on-line December 2012, doi:10.1073/pnas.1216039110

2. Blower, TR., et al (2012) Viral evasion of a bacterial altruistic suicide system through RNA-based molecular mimicry enables infectious altruism. PloS Genetics, 8(10): e1003023. doi:10.1371/journal.pgen.1003023

3. Matilla, MA et al (2012) Bacterial gene clusters encoding the anti-cancer haterumalide class of molecules: biogenesis of the broad spectrum antifungal and anti-oomycete compound, oocydin A. Journal of Biological Chemistry, 287: 39125-39138

4. Blower, TR., et al (2012) Identification and classification of bacterial Type III toxin-antitoxin systems encoded in chromosomal and plasmid genomes. Nucleic Acids Research, 40, 6158-6173.

5. Ramsay, J., et al (2011) A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium. PNAS, USA 108, 14932-14937

6. Blower, T., et al (2011) A processed non-coding RNA regulates an altruistic bacterial antiviral system.  Nature Structural and Molecular Biology 18, 185-190

7. Chawrai, SR., et al (2011) Characterisation of PigC and HapC, the prodigiosin synthetases from Serratia sp. and Hahella chejuensis with potential for biocatalytic production of anticancer agents. Chemical Science 3, 447-454

8. Poulter, S., et al (2011) The Serratia LuxR-family quorum sensing regulator, CarR, activates transcription in the absence of N-acyl homoserine lactone signals. Molecular Microbiology, doi: 10.1111/j.1365-2958.2011.07634.x

9. Petty, NK., et al (2011) Citrobacter rodentium is an unstable pathogen showing evidence of significant genomic flux. PloS Pathogens 10.1371/journal.ppat.1002018

10. Pérez-Mendoza, D, et al (2011) A multi-repeat adhesin of the phytopathogen, Pectobacterium atrosepticum, is secreted by a Type I pathway and is subject to complex regulation involving a non-canonical diguanylate cyclase. Molecular Microbiology 82, 719-733.

11. Fineran, P., et al (2009) The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. PNAS, USA, 106: 894-899

12. 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

13. 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

Reviews:

1. Williamson, N., et al (2006) The biosynthesis and regulation of bacterial prodiginines. Nature Reviews Microbiology, 4, 887-899

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

3. Whitehead, N., et al (2001) Quorum sensing in Gram-negative bacteria. FEMS Microbiological Reviews, 25, 365-404