Learning the Language of Bacteria

Abstract

remarkable change to the classical view of the microbial world has become apparent over the last few decades. Rather than bacteria being seen as purely single-celled organisms, existing in isolation, it has become clear that bacteria mainly crowd together in highly complex, multispecies communities. Moreover, they actually "talk" to one another by using small molecules. In Gram-negative bacteria, these small molecules are commonly N-acylated homoserine lactones (AHLs). The design and synthesis of AHL analogues have been performed by many groups (1-8) on a more or less ad hoc basis, making it difficult to draw any firm conclusions about structureactivity relationships and species selectivity. Blackwell and co-workers (9) now report a comprehensive and systematic study that compares the activities of ϳ100 AHL analogues across three species. This not only

Quorum Sensing in Gram-Negative Bacteria: Small-Molecule Modulation of AHL and AI-2 Quorum Sensing Pathways

“…[54][55][56][57] Therefore, the LasR receptor is usually the main focus for activator or inhibitor development and biochemical studies in P. aeruginosa (see below). 31 Nevertheless, the general principles of AHL-based quorum sensing outlined in Figure 1 are applicable to the majority of Gram-negative species. Thus, a LuxI-type protein produces a diffusible AHL ligand; above a certain threshold ligand concentration, productive binding of the ligand to its cognate cytoplasmic receptor (a LuxR-type protein) occurs and the resulting AHL-LuxR-type protein complex then modulates the expression of target genes that are involved in bacterial group processes.…”

“…12,28,110 High-throughput synthesis has proven to be a particularly valuable tool in identifying biologically active synthetic AHL mimics and the elucidation of structure-activity trends, as libraries of AHL analogues with systematic modifications can be synthesized and tested in a time-and cost-efficient fashion. 7,12,31,114 …”

“…31,110 The lack of comparative investigations of non-native AHL function across multiple bacterial species has resulted in a relative paucity of information pertaining to the molecular features that confer selectivity or broad-range activity to synthetic quorum sensing modulators in Gram-negative bacteria. 12 In recent seminal reports, Blackwell and co-workers presented a comprehensive and systematic study that directly compared the activities of ∼90 AHL analogues across three Gramnegative bacterial species: the pathogens A. tumefaciens and P. aeruginosa and the symbiont V. fischeri.…”

Medical biofilms

“…Once at a substratum surface, bacterial cells adhere by non-specific and/or specific receptor:ligand adhesion mechanisms (An and Friedman, 1998;Busscher et al, 1992;Glantz et al, 1999). Within minutes of attachment, adherent cells up-regulate the secretion of certain cell signal molecules that orchestrate communitywide phenotypic responses, through a process termed quorum sensing (Bjarnsholt and Givskov, 2007;Camilli and Bassler, 2006;Davies et al, 1998;Harraghy et al, 2007;Hodgkinson et al, 2007;Horswill et al, 2007;Pritchard, 2006;Rumbaugh, 2007). Such population responses include the up-regulation of virulence factors (Branda et al, 2005;Otto, 2006) and secretion of extracellular polymers (Davies and Geesey, 1995;Davies et al, 1993;Hall-Stoodley and Stoodley, 2005).…”

Preventing Biofilm Formation on Biomedical Surfaces

“…Within minutes of irreversible attachment, adherent cells up-regulate the secretion of certain cell signaling molecules that manipulate phenotypic responses, through a process termed 'quorum sensing' [17][18][19] (step 4 in Figure 7.2), which leads to stronger cellular response to a molecular stimulus, due to an increase in the number of receptors on the cell surface, that is, up-regulation of virulence factors of the pathogenic bacteria [20] and secretion of extracellular polymers [21] to bind the microcolonies together into a robust biofilm. Virulence factors are molecules produced by a pathogen that specifically cause disease, or that influence their host's function in order to allow the pathogen to thrive.…”