Quorum Sensing 101


Quorum Sensing. Bacteria synthesize and secrete autoinducers, low MW molecules that diffuse away into the surroundings. Bacteria in the environment sense the local density of these autoinducers via quorum sensing receptors. Above a certain concentration threshold, binding of the autoinducer ligand is synchronized among bacteria. The binding event is transduced into transcriptional and translational changes that result in coordinated shifts in group behavior, e.g. conjugation, biofilm formation, sporulation and competence.1

Quorum sensing in Vibrio fischeri

LuxIR2LuxI synthesizes acylated homoserine lactone (AHL) autoinducers (shown as pentagons) which freely diffuse across the bacterial cell membrane.2,3 At high cell density, autoinducer concentration increases in the cell’s local environment, increasing the number of binding events of AHL to the cytoplasmic receptor LuxR.4 LuxR-AHL acts as a transcriptional activator of luciferase genes luxICDABE, binding to the “lux box” upstream of the operon.5 The expression of luciferase results in bioluminescence.

Gene expression is partly controlled by the rapid degradation of the LuxR receptor when unbound to autoinducer, allowing for tight regulation of receptor levels.5 Additionally, positive feedback loops, considered a hallmark of quorum sensing systems, enforce the synchrony of group behaviors.6  The autoinducer synthase gene luxI is controlled by the lux box; therefore at HCD with high levels of the transcriptional activator LuxR-AHL, LuxI is upregulated and more autoinducer is produced. This autoinduction positive feedback of LuxI exponentially increases AHL levels, coordinating bioluminescence among the local cell population.1

Click here to watch Dr. Bonnie Bassler (who discovered quorum system in V. harveyi in 1993) discuss the symbiotic bioluminescence of V. fischeri in the Hawaiian bobtail squid.

What do autoinducers look like?


Autoinducers can have a variety of chemical structures. (1) Oligopeptides are mainly found in gram-positive bacteria. These genetically encoded molecules vary mostly in length and primary structure, but they can also undergo cyclization and other species-specific processing.1 (2) N-Acyl homoserine lactone (AHL) is likewise found mainly in gram-negative bacteria. In contrast with oligopeptides, AHLs are hypothesized to function exclusively in intraspecies cellular communication networks.7 In Vibrio cholerae, a structurally related molecule CAI-1 is synthesized.8 In both cases, the variety and specificity of the signaling molecules depend on the length and structure of the incorporated acyl moiety. Thus, autoinducer synthesis is directly linked with lipid metabolism in these species. (3) Autoinducer-2  (AI-2) is a tetrahydroxytetramethoxyfuran (THMF) that can form a bicyclic borate diester in the presence of boron.9,10 AI-2 and its cognate receptor are common to many different species, thereby enabling interspecies “cross talk”. Parallel quorum sensing systems allow detection and integration of cell-density signals for both intra- and interspecies coordination of behavior.11 This so-called species complexity helps bacterial subpopulations determine whether to compete, collaborate or simply coexist with other bacteria in the local milieu.

What types of behaviors are regulated by QS?


Many functions integral for survival are mediated by quorum sensing. Generally, these behaviors can be viewed as group-dependent or group-beneficial. For example, symbiotic bioluminescence in V. fischeri and E. scolopes requires synchronous, population-wide activation of the light-producing luciferase to produce enough light for its nocturnal host to thwart detection.12 Similarly, conjugation inherently requires both donor and recipient. Biofilm formationsporulation and motility are essential to survival of the population as a whole, enabling bacteria to respond rapidly to changes in the environment. Competence further contributes to population fitness by increasing genetic diversity, enabling catabolism of extracellular nucleic acids and repairing DNA damage.13 Finally, antibiotic production, as seen in Pseudomonas aeruginosa, combats opportunistic infection by foreign bacteria and promotes the survival of one species over another.14

Arguably the most complex and clinically relevant behavior regulated by quorum sensing is virulence. Because of the diversity of pathogenic bacteria, pathologies can vary considerably. Generally speaking, virulence factors are agents produced and released by a pathogen that enable it to establish a successful infection in a host. Pathogenicity can involve immunosuppression, immunoevasion, colonization of a niche in the host, nutrient acquisition to ensure viability and the release of toxins (causing direct damage to the host or defending against other microorganisms). Accordingly, virulence programs can include some of the aforementioned collective behaviors seen also in non-pathogenic bacteria, in addition to species-specific phenotypes. While we might expect larger bacterial populations to be more likely to launch an attack and even to be more successful in establishing an infection, this is not always the case. In fact, virulence factors are produced at low cell densities and downregulated at high cell densities in V. cholerae, the causative agent of cholera. 

Why might this be the case and what other behaviors are regulated by QS in V. cholerae? Click here to learn more.

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