Molecular microbiology: bacterial quorum sensing, virulence, protein secretion, antibiotics, gas vesicles and flotation, toxin-antitoxin systems and bacteriophage abortive infection.
Our research involves multiple aspects of molecular microbiology including quorum sensing (QS), virulence in bacterial pathogens, regulation and biosynthesis of antibiotics and other secondary metabolites, protein secretion systems, gas vesicles and flotation, bacteriophages, toxin-antitoxin systems and anti-viral abortive infection. We work on various Gram-negative enterobacteria, including the phytopathogens, Erwinia (Pectobacterium) and Dickeya, Serratia species (which can be opportunistic human pathogens) Citrobacter rodentium (the murine pathogen), Yersinia and a spectrum of phages infecting bacteria of medical, agricultural or industrial biotechnology interest (including Pseudomonas and Streptomyces).
We study 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. 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, andrimid, haterumalides/oocydins and zeamines in enterobacteria such as Erwinia (Pectobacterium), Dickeya, Serratia, Pantoea, and other rhizosphere organisms. We use genetics, and 'omics to investigate the physiological impacts of environmental signaling in the regulation of virulence and antibacterial and antifungal antibiotic production in Pectobacterium, Dickeya, Serratia and Pantoea. We also investigate molecular processes involved in virulence factor secretion. We are characterising and exploiting new bacteriophages for the development of genetic tools in functional genomics, for synthetic biology, and for the analysis of bacterial surface receptors and the evolution of viral host range. We are also studying phage abortive infection (Abi) 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 & Visitors: Rita Monson, Nathalie Goeders, Sarah Barker, Alison Rawlinson, Chin Mei Lee, Bihe Chen, Ray Chai, Alex Quintero, Andy Day, Megan Booth, Ziyue Zeng, Samuel Magaziner, Annabel Murphy, Maxime Couturier, Joseph Honger, Amalia Soenens Martinez De Murguia
Some key publications:
1. Rao, F., et al (2015) Co-evolution of quaternary organization and novel RNA tertiary interactions revealed in the crystal structure of a bacterial protein-RNA toxin-antitoxin system. Nucleic Acids Research, doi: 10.1093/nar/gkv868
2. Matilla, M., et al (2014) Viunalikeviruses are environmentally common agents of horizontal gene transfer in pathogens and biocontrol bacteria. ISME Journal. doi:10.1038/ismej.2014.150
3. 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
4. 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
5. 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
6. 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.
7. 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
8. Blower, T., et al (2011) A processed non-coding RNA regulates an altruistic bacterial antiviral system. Nature Structural and Molecular Biology 18, 185-190
9. 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
10. 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
11. Petty, NK., et al (2011) Citrobacter rodentium is an unstable pathogen showing evidence of significant genomic flux. PloS Pathogens 10.1371/journal.ppat.1002018
12. 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.
13. Fineran, P., et al (2009) The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. PNAS, USA, 106: 894-899
14. 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
15 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
Some reviews:
- Salmond, GPC and Fineran, P (2015) A century of the phage: past, present and future. Nature Reviews Microbiology (doi:10.1038/nrmicro3564)
- Dy, R., et al (2014) Remarkable mechanisms in microbes to resist phage infections. Annual Reviews of Virology. (doi: 10.1146/annurev-virology-031413-085500)
- O’Connell, KMG., et al (2013) Combating multi-drug resistant bacteria: current strategies for the discovery of novel antibacterials. Angewante Chemie (DOI: 10.1002/anie.201209979)
- Williamson, N., et al (2006) The biosynthesis and regulation of bacterial prodiginines. Nature Reviews Microbiology, 4, 887-899
- Coulthurst, S., et al (2005) Regulation and biosynthesis of carbapenem antibiotics in bacteria. Nature Reviews Microbiology 3:295-306
- Whitehead, N., et al (2001) Quorum sensing in Gram-negative bacteria. FEMS Microbiological Reviews, 25, 365-404