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Functional analysis of luxS in Staphylococcus aureus reveals a role in metabolism but not quorum sensing.

The function of AI-2 in many bacteria and the physiological role of LuxS, the enzyme responsible for its production, remain matters of debate. Here, we show that in Staphylococcus aureus the luxS gene forms a monocistronic transcriptional unit under the control of a sigma(70)-dependent promoter. The gene was transcribed throughout growth under a variety of conditions, including intracellular growth in MAC-T cells. AI-2 was produced in rich media under aerobic and anaerobic conditions, peaking during the transition to stationary phase, but was hardly detectable in a sulfur-limited defined medium. In the presence of glucose or under anaerobic conditions, cultures retained considerable AI-2 activity after entry into stationary phase. Inactivation of luxS in various S. aureus strains did not affect virulence-associated traits, such as production of hemolysins and extracellular proteases, biofilm formation, and the agr signaling system. Conversely, AI-2 production remained unchanged in an agr mutant. However, luxS mutants grown in a sulfur-limited defined medium exhibited a growth defect. When grown together with the wild type in mixed culture, luxS mutants of various S. aureus strains showed reduced ability to compete for growth under these conditions. In contrast, a complemented luxS mutant grew as well as the parent strain, suggesting that the observed growth defect was of an intracellular nature and had not been caused by either second-site mutations or the lack of a diffusible factor. However, the LuxS/AI-2 system does not appear to contribute to the overall fitness of S. aureus RN6390B during intracellular growth in epithelial cells: the wild type and a luxS mutant showed very similar growth patterns after their internalization by MAC-T cells.

Aerobiosis↗

Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators.

The importance of accurate demographic information is reflected in the United States Constitution, Article 1, which provides for a decennial census of this country's human population. Bacteria also conduct a census of their population and do so more frequently, more efficiently, and as far we know, with little if any of the political contentiousness caused by human demographers. Many examples have been found of particular bacterial genes, operons, or regulons that are expressed preferentially at high cell densities. Many of these are regulated by proteins related to the LuxR and LuxI proteins of Vibrio fischeri, and by a diffusible pheromone called an autoinducer. LuxR and LuxI and their cognate autoinducer (3-oxohexanoyl homoserine lactone, designated VAI-1) provide an important model to describe the functions of this family of proteins. LuxR is a VAI-1 receptor and a VAI-1-dependent transcriptional activator, and LuxI directs the synthesis of VAI-1. VAI-1 diffuses across the bacterial envelope, and intracellular concentrations of it are therefore strongly increased by nearby VAI-1-producing bacteria. Similar systems regulate pathogenesis factors in Pseudomonas aeruginosa and Erwinia spp., as well as T1 plasmid conjugal transfer in Agrobacterium tumefaciens, and many other genes in numerous genera of gram-negative bacteria. Genetic analyses of these systems have revealed a high degree of functional conservation, while also uncovering features that are unique to each.

4-Butyrolactone↗

[The role of "quorum sensing" regulation system in symbiotic interaction of bacteria Burkholderia cepacia and Pseudomonas aeruginosa during mixed infection].

Data concerning mechanisms of strengthening virulence of bacteria B.cepacia and P.aeruginosa during experimental mixed-infection are submitted. Results of in vitro studies of acylhomoserine lactones (AHL) with various length of a carbon lateral circuit have shown that butanoyl-homoser-ine lactone (C4), hexanoyl-homoserine lactone (C6) and octanoyl-homoserine lactone (C8) separately and in various combinations display different effects on growth of bacteria, formation of colonies and production of pathogenicity factors. Experiments on animals have shown strengthening virulence of bacteria B.cepacia by C4, C6 and C8 lactones when introduced simultaneously. Strengthening of virulence of the P.aeruginosa strain under the action of lactone C6 and simultaneous action of C4, C6 and C8 lactones was observed. The data obtained give grounds for assumption, that bacteria may use exogenous lactones, including those produced by closely related bacteria, during their life cycle.

4-Butyrolactone↗

Recent advances in biology: intercellular communication and quorum sensing in micro-organisms.

N-acyl-L-homoserine lactones are involved as intercellular signalling agents controlling a wide range of physiological responses in Gram-negative bacteria. They function especially in vibrios, pseudomonads and erwinias as well as in Rhizobium and Agrobacterium spp, particularly where the bacteria are in symbiotic or parasitic relationships with higher organisms. Several Gram-negatives, such as Escherichia coli, do not, however, appear to produce or respond to AHLs and they may have other intercellular signalling molecules. The present review reports that several stress related responses in E. coli can be induced by supernatant fluids from cultures which have already induced the response. In some cases at least, the active agents in the supernatant fluids are proteins rather than AHLs.

Cell Division↗

LuxS is required for persistent pneumococcal carriage and expression of virulence and biosynthesis genes.

Streptococcus pneumoniae causes several diseases, including otitis media, pneumonia, and meningitis. Although little is known about the regulation of or how individual pneumococcal factors contribute to these disease states, there is evidence suggesting that some factors are regulated by a cell-density-dependent mechanism (quorum sensing). Quorum sensing allows bacteria to couple transcription with changes in cell density; bacteria achieve this by sensing and responding to small diffusible signaling molecules. We investigated how the LuxS signaling system impacts the biology of S. pneumoniae. An analysis of the transcriptional profiles of a serotype 2 strain and an isogenic luxS deletion strain utilizing an S. pneumoniae-specific microarray indicated that LuxS regulates gene expression involved in discrete cellular processes, including pneumolysin expression. Contrary to the paradigm for quorum sensing, we observed pronounced effects on transcription in early log phase, where gene expression was repressed in the mutant. Assessing the mutant for its ability to infect and cause disease in animals revealed a profound defect in ability to persist in the nasopharyngeal tissues. Our analysis of an S. pneumoniae transcriptome revealed a function for LuxS in gene regulation that is not dependent upon high cell density and is likely involved in the maintenance of pneumococcal load in susceptible hosts.

Bacterial Proteins↗

Inter-kingdom signaling: deciphering the language of acyl homoserine lactones.

Bacteria use small secreted chemicals or peptides as auto-inducers to coordinately regulate gene expression within a population in a process called quorum sensing. Quorum sensing controls several important functions in different bacterial species, including the production of virulence factors and biofilm formation in Pseudomonas aeruginosa and bioluminescence in Vibrio fischeri. Many gram-negative bacterial species use acyl homoserine lactones as auto-inducers that function as ligands for transcriptional regulatory proteins. Several recent reports indicate that bacterial acyl homoserine lactones can also affect gene expression in host cells. Direct signaling also appears to function in the opposite direction as some eukaryotic cell types produce mimics that interact with quorum sensing systems in bacteria. Here, we will describe the evidence to support the existence of bi-directional inter-kingdom signaling via acyl homoserine lactones and eukaryotic mimics and discuss the potential molecular mechanisms that mediate these responses. The functional consequences of inter-kingdom signaling will be discussed in relation to both pathogenic and non-pathogenic bacterial-host interactions.

4-Butyrolactone↗