For many years bacteria were considered primarily as autonomous unicellular organisms with little capacity for collective behaviour. However, we now appreciate that bacterial cells are in fact, highly communicative. The generic term ‘quorum sensing’ has been adopted to describe the bacterial cell-to-cell communication mechanisms which co-ordinate gene expression usually, but not always, when the population has reached a high cell density. Quorum sensing depends on the synthesis of small molecules (often referred to as pheromones or autoinducers) that diffuse in and out of bacterial cells. As the bacterial population density increases, so does the synthesis of quorum sensing signal molecules, and consequently, their concentration in the external environment rises. Once a critical threshold concentration has been reached, a target sensor kinase or response regulator is activated (or repressed) so facilitating the expression of quorum sensing-dependent genes. Quorum sensing enables a bacterial population to mount a co-operative response that improves access to nutrients or specific environmental niches, promotes collective defence against other competitor prokaryotes or eukaryotic defence mechanisms and facilitates survival through differentiation into morphological forms better able to combat environmental threats. Quorum sensing also crosses the prokaryotic–eukaryotic boundary since quorum sensing-dependent signalling can be exploited or inactivated by both plants and mammals.

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Look who's talking: communication and quorum sensing in the bacterial world

It has been suggested that bacterial cells communicate by releasing and sensing small diffusible signal molecules in a process commonly known as quorum sensing (QS). It is generally assumed that QS is used to coordinate cooperative behaviours at the population level. However, evolutionary theory predicts that individuals who communicate and cooperate can be exploited. Here we examine the social evolution of QS experimentally in the opportunistic pathogen Pseudomonas aeruginosa, and show that although QS can provide a benefit at the group level, exploitative individuals can avoid the cost of producing the QS signal or of performing the cooperative behaviour that is coordinated by QS, and can therefore spread. We also show that a solution to the problem of exploitation is kin selection, if interacting bacterial cells tend to be close relatives. These results show that the problem of exploitation, which has been the focus of considerable attention in animal communication, also arises in bacteria.

Cooperation and conflict in quorum-sensing bacterial populations

Our understanding of the social lives of microbes has been revolutionized over the past 20 years. It used to be assumed that bacteria and other microorganisms lived relatively independent unicellular lives, without the cooperative behaviors that have provoked so much interest in mammals, birds, and insects. However, a rapidly expanding body of research has completely overturned this idea, showing that microbes indulge in a variety of social behaviors involving complex systems of cooperation, communication, and synchronization. Work in this area has already provided some elegant experimental tests of social evolutionary theory, demonstrating the importance of factors such as relatedness, kin discrimination, competition between relatives, and enforcement of cooperation. Our aim here is to review these social behaviors, emphasizing the unique opportunities they offer for testing existing evolutionary theory as well as highlighting the novel theoretical problems that they pose.

https://synergy.st-andrews.ac.uk/gardner/files/2015/05/West_et_al_2007.pdf

The Social Lives of Microbes

Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules

Although unicellular, bacteria are highly interactive and employ a range of cell-to-cell communication or ‘quorum sensing (QS)’ systems for promoting collective behaviour within a population. QS is generally considered to facilitate gene expression only when the population has reached a sufficient cell density and depends on the synthesis of small molecules that diffuse in and out of bacterial cells. As the bacterial population density increases, so does the synthesis of QS signal molecules and consequently, their concentration in the external environment increases. Once a critical threshold concentration is reached, a target sensor kinase or response regulator is activated, so facilitating the expression of QS-dependent target genes. Several chemically distinct families of QS signal molecules have been described, of which the N-acylhomoserine lactone (AHL) family in Gram-negative bacteria have been the most intensively investigated. QS contributes to environmental adaptation by facilitating the elaboration of virulence determinants in pathogenic species and plant biocontrol characteristics in beneficial species as well as directing biofilm formation and colony escape. QS also crosses the prokaryotic–eukaryotic boundary in that QS signal molecules influence the behaviour of eukaryotic organisms in both the plant and mammalian worlds such that QS signal molecules may directly facilitate bacterial survival by promoting an advantageous lifestyle within a given environmental niche.

Quorum sensing, communication and cross-kingdom signalling in the bacterial world

Comparative immune modulatory activity for a range of synthetic analogues of a Pseudomonas aeruginosa signal molecule, N-(3-oxododecanoyl)-l-homoserine lactone (3O, C12-HSL), is described. Twenty-four single or combination systematic alterations of the structural components of 3O, C12-HSL were introduced as described. Given the already defined immunological profile of the parent compound, 3O, C12-HSL, these compounds were assayed for their ability to inhibit murine and human leucocyte proliferation and TNF-α secretion by lipopolysaccharide (LPS) stimulated human leucocytes in order to provide an initial structure−activity profile. From IC50 values obtained with a murine splenocyte proliferation assay, it is apparent that acylated l-homoserine lactones with an 11−13 C side chain containing either a 3-oxo or a 3-hydroxy group are optimal structures for immune suppressive activity. These derivatives of 3O, C12-HSL with monounsaturation and/or a terminal nonpolar substituent on the side chain were also potent...

Synthetic analogues of the bacterial signal (quorum sensing) molecule N-(3-oxododecanoyl)-L-homoserine lactone as immune modulators.

N-acylhomoserine lactones (AHLs) are small, diffusible signalling molecules, employed by Gram-negative bacteria to coordinate gene expression with cell population density. Recent in vitro findings indicate that AHLs may function as virulence determinants per se, through modification of cytokine production by eukaryotic cells, and by stimulating the relaxation of blood vessels.




In the present study, we assessed the influence of AHLs on cardiovascular function in conscious rats, and draw attention to the ability of the N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), a signal molecule produced by P. aeruginosa, to cause marked bradycardia. This bradycardic effect was blocked by atropine and atenolol, and did not occur in vitro. Furthermore, modification of the acyl side chain length resulted in the loss of activity, whereas removal of the homoserine lactone ring, did not. The bradycardic effect of 3-oxo-C12-HSL was also observed in endotoxaemic animals, albeit attenuated.




In normal rats, 3-oxo-C12-HSL caused initial mesenteric and hindquarters vasoconstriction, but only slight, and delayed signs of vasodilatation in the renal and mesenteric vascular beds. Furthermore, administration of 3-oxo-C12-HSL (pre-treatment or 2 h post-treatment) together with LPS, did not modify the established regional haemodynamic effects of the LPS, 6 h after the onset of its infusion.




Our observations do not provide any clear evidence for an ability of 3-oxo-C12-HSL to modify the haemodynamic responses to LPS infusion. However, they are not inconsistent with the hypothesis that some of the cardiovascular sequelae of bacterial infection may be modulated by an influence of bacterial quorum sensing signalling molecules on the host.






British Journal of Pharmacology (2001) 133, 1047–1054; doi:10.1038/sj.bjp.0704174

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0704174

Haemodynamic effects of the bacterial quorum sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, in conscious, normal and endotoxaemic rats.

Christopher Harty

Papers

Synthetic analogues of the bacterial signal (quorum sensing) molecule N-(3-oxododecanoyl)-L-homoserine lactone as immune modulators.

Haemodynamic effects of the bacterial quorum sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, in conscious, normal and endotoxaemic rats.

Bacterial Evasion of Host Immune Responses: Bacterial quorum sensing signalling molecules as immune modulators