Regulation of virulence and biofilm formation by quorum sensing and the "stress alarmone" ppGpp in gram-negative pathogenic bacteria.
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About the project
About the Project We are investigating the complex interplay between cell-cell signalling (quorum sensing), microbial lifestyle (i.e., free-living planktonic cultures vs sessile biofilm communities), growth phase and virulence in gram-negative bacteria. We work on two genetically-amenable pathogens: the opportunstic human pathogen Pseudomonas aeruginosa (the scourge of hospital clinicians and a major cause of morbidity and mortality in individuals with cystic fibrosis) and Erwinia atroseptica, an economically important plant pathogen. In spite of their different target hosts, both pathogens use very similar mechanisms to regulate their virulence. We are combining the techniques of "classical" molecular microbiology (such as targetted construction of mutants, over-expression constructs, transposon mutageneses etc) with newer technologies including whole genome sequencing and functional genomics (metabolomics, proteomics, microarray analyses etc) to investigate how virulence and lifestyle decisions are regulated in these pathogens. Recent data indicate that at the top of the hierarchy of regulatory factors in these organisms lies an "apex regulator", ppGpp. This "stress alarmone" is made when the cells become limited for nutrients, and appears to be an ancestral regulatory system that pre-dates the more widely studied (but sub-ordinate) regulatory mechanism known as "quorum sensing".