The molecule 2-heptyl-3-hydroxy-4-quinolone, also named the Pseudomonas quinolone signal (PQS), has been discovered as an intracellular link between the two major quorum sensing systems of P. aeruginosa; the las and rhl systems. [1] These systems together control expression of virulence factors and play a major role in the formation of biofilms in Pseudomonas aeruginosa. P. aeruginosa is a gram-negative bacteria and opportunistic human pathogen that can cause serious and sometimes fatal infections in humans. [2] Similar to other bacterial species, P. aeruginosa uses quorum sensing (QS) systems to communicate between cells in a population. [1] This allows coordination of gene expression in a population based on changing cell densities, abundance of nutrients, and other environmental factors.
The functional units of quorum sensing are called autoinducers, which are communicatory molecules that can induce conformist actions among a group. Specific autoinducers are used to influence the group in certain ways, upregulating specific functions while suppressing others. In response to a received signal, the target cell will upregulate the production and release of the same autoinducer. This creates a positive feedback cascade in which all proximal cells will express similar metabolic adjustments, morphological characteristics, and motility. [3]
The Pseudomonas Quinolone Signal (PQS) provides a link between the las and rhI quorum sensing systems. [4] The las system regulates the lasB gene that encodes the lasB elastase enzyme. The lasB elastase enzyme is a secreted protease that functions in causing tissue damage to the host. This exo-protease is able to degrade various plasma proteins such as immunoglobulins, coagulation complement factors, and alpha-proteinase inhibitors. [5] The rhI system regulates the rhII gene which encodes for C4-HSL synthase which plays a significant role in biofilm formation. [6]
Only select bacterium can utilize Quorum sensing in their biofilm production; among the predominant users is P. aeruginosa and the genus Burkholderia to form biofilms. Biofilms are important in all aspects of life and are readily abundant in nearly all environments. They are densely populated with several different survivable microenvironments and can often sort based on optimal metabolic location in accordance with metabolites and byproducts. [7] PQS has also been discovered to play a role in mediating denitrification, [8] [9] iron acquisition and cytotoxicity for the cell. [10]
A biofilm is an syntrophic community of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymeric substances (EPSs). The cells within the biofilm produce the EPS components, which are typically a polymeric combination of extracellular polysaccharides, proteins, lipids and DNA. Because they have three-dimensional structure and represent a community lifestyle for microorganisms, they have been metaphorically described as "cities for microbes".
In biology, quorum sensing or quorum signaling (QS) is the ability to detect and respond to cell population density by gene regulation. Quorum sensing is a type of cellular signaling, and more specifically can be considered a type of paracrine signaling. However, it also contains traits of both autocrine signaling: a cell produces both the autoinducer molecule and the receptor for the autoinducer. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at which the resulting phenotypes will be most beneficial, especially for phenotypes that would be ineffective at low cell densities and therefore too energetically costly to express. Many species of bacteria use quorum sensing to coordinate gene expression according to the density of their local population. In a similar fashion, some social insects use quorum sensing to determine where to nest. Quorum sensing in pathogenic bacteria activates host immune signaling and prolongs host survival, by limiting the bacterial intake of nutrients, such as tryptophan, which further is converted to serotonin. As such, quorum sensing allows a commensal interaction between host and pathogenic bacteria. Quorum sensing may also be useful for cancer cell communications.
N-Acyl homoserine lactones are a class of signaling molecules involved in bacterial quorum sensing, a means of communication between bacteria enabling behaviors based on population density.
A slime layer in bacteria is an easily removable, unorganized layer of extracellular material that surrounds bacteria cells. Specifically, this consists mostly of exopolysaccharides, glycoproteins, and glycolipids. Therefore, the slime layer is considered as a subset of glycocalyx.
Pseudomonas aeruginosa is a common encapsulated, Gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes. P. aeruginosa is able to selectively inhibit various antibiotics from penetrating its outer membrane - and has high resistance to several antibiotics, according to the World Health Organization P. aeruginosa poses one of the greatest threats to humans in terms of antibiotic resistance.
The PrrF RNAs are small non-coding RNAs involved in iron homeostasis and are encoded by all Pseudomonas species. The PrrF RNAs are analogs of the RyhB RNA, which is encoded by enteric bacteria. Expression of the PrrF RNAs is repressed by the ferric uptake regulator (Fur) when cells are grown in iron-replete conditions. Under iron limitation, the PrrF RNAs are expressed and act to negatively regulate several genes encoding iron-containing proteins, including SodB and succinate dehydrogenase. As such, PrrF regulation "spares" iron when this nutrient becomes scarce.
Swarming motility is a rapid and coordinated translocation of a bacterial population across solid or semi-solid surfaces, and is an example of bacterial multicellularity and swarm behaviour. Swarming motility was first reported by Jorgen Henrichsen and has been mostly studied in genus Serratia, Salmonella, Aeromonas, Bacillus, Yersinia, Pseudomonas, Proteus, Vibrio and Escherichia.
Autoinducers are signaling molecules that are produced in response to changes in cell-population density. As the density of quorum sensing bacterial cells increases so does the concentration of the autoinducer. Detection of signal molecules by bacteria acts as stimulation which leads to altered gene expression once the minimal threshold is reached. Quorum sensing is a phenomenon that allows both Gram-negative and Gram-positive bacteria to sense one another and to regulate a wide variety of physiological activities. Such activities include symbiosis, virulence, motility, antibiotic production, and biofilm formation. Autoinducers come in a number of different forms depending on the species, but the effect that they have is similar in many cases. Autoinducers allow bacteria to communicate both within and between different species. This communication alters gene expression and allows bacteria to mount coordinated responses to their environments, in a manner that is comparable to behavior and signaling in higher organisms. Not surprisingly, it has been suggested that quorum sensing may have been an important evolutionary milestone that ultimately gave rise to multicellular life forms.
Lactonase (EC 3.1.1.81, acyl-homoserine lactonase; systematic name N-acyl-L-homoserine-lactone lactonohydrolase) is a metalloenzyme, produced by certain species of bacteria, which targets and inactivates acylated homoserine lactones (AHLs). It catalyzes the reaction
Pyocyanin (PCN−) is one of the many toxic compounds produced and secreted by the Gram negative bacterium Pseudomonas aeruginosa. Pyocyanin is a blue secondary metabolite, turning red below pH 4.9, with the ability to oxidise and reduce other molecules and therefore kill microbes competing against P. aeruginosa as well as mammalian cells of the lungs which P. aeruginosa has infected during cystic fibrosis. Since pyocyanin is a zwitterion at blood pH, it is easily able to cross the cell membrane. There are three different states in which pyocyanin can exist: oxidized (blue), monovalently reduced (colourless) or divalently reduced (red). Mitochondria play an important role in the cycling of pyocyanin between its redox states. Due to its redox-active properties, pyocyanin generates reactive oxygen species.
In molecular biology, the LuxR-type DNA-binding HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 65 amino acids. It is present in transcription regulators of the LuxR/FixJ family of response regulators. The domain is named after Vibrio fischeri luxR, a transcriptional activator for quorum-sensing control of luminescence. LuxR-type HTH domain proteins occur in a variety of organisms. The DNA-binding HTH domain is usually located in the C-terminal region of the protein; the N-terminal region often containing an autoinducer-binding domain or a response regulatory domain. Most luxR-type regulators act as transcription activators, but some can be repressors or have a dual role for different sites. LuxR-type HTH regulators control a wide variety of activities in various biological processes.
Rhamnolipids are a class of glycolipid produced by Pseudomonas aeruginosa, amongst other organisms, frequently cited as bacterial surfactants. They have a glycosyl head group, in this case a rhamnose moiety, and a 3-(hydroxyalkanoyloxy)alkanoic acid (HAA) fatty acid tail, such as 3-hydroxydecanoic acid.
Interspecies quorum sensing is a type of quorum sensing in which bacteria send and receive signals to other species besides their own. This is accomplished by the secretion of signaling molecules which trigger a response in nearby bacteria at high enough concentrations. Once the molecule hits a certain concentration it triggers the transcription of certain genes such as virulence factors. It has been discovered that bacteria can not only interact via quorum sensing with members of their own species but that there is a kind of universal molecule that allows them to gather information about other species as well. This universal molecule is called autoinducer 2 or AI-2.
PhrS is a bacterial small RNA found in Pseudomonas aeruginosa. It was first identified in a RNAomics screen and has since been found to act as a link between oxygen availability and quorum sensing.
Acyl-homoserine-lactone synthase is an enzyme with systematic name acyl-(acyl-carrier protein):S-adenosyl-L-methionine acyltranserase . This enzyme catalyses the following chemical reaction
Delftia tsuruhatensis is a Gram-negative, rod-shaped, catalase- and oxidase-positive, motile bacterium from the Comamonadaceae family. It was first isolated from a wastewater treatment plant in Japan in 2003. D. tsuruhatensis is an opportunistic and emergent pathogen. All documented human infections are healthcare-associated.
Everett Peter Greenberg is an American microbiologist. He is the inaugural Eugene and Martha Nester Professor of Microbiology at the Department of Microbiology of the University of Washington School of Medicine. He is best known for his research on quorum sensing, and has received multiple awards for his work.
Kalai Mathee is a professor at Florida International University, joint editor-in-chief of the Journal of Medical Microbiology, and an elected fellow of the American Academy of Microbiology. She is known for her research on bacterial infections caused by Pseudomonas aeruginosa.
Diffusible signal factor (DSF) is found in several gram-negative bacteria and play a role in the formation of biofilms, motility, virulence, and antibiotic resistance. Xanthomonas campestris was the first bacteria known to have DSF. The synthesis of the DSF can be seen in rpfF and rpfB enzymes. An understanding of the DSF signaling mechanism could lead to further disease control.