The growth and proliferation of bacteria is largely dependent on their ability to communicate with each other through a well orchestrated process known as quorum sensing. The signalling between different bacterial species or within species takes place through this phenomenon via the release of molecules called auto-inducers.
The process has been found significant and can’t be done away with respect to bacterial growth and function as it provides them important information and gives the bacteria a measure of the surrounding population density, allows them to organize gene expression coordination on behalf of the entire population during conditions of stress or starvation that might bring about a change in the size of the community or the niche conditions.
The bacteria are also able to gather enough information regarding nutrient availability and prevalent ecological conditions and act accordingly. It has been established that the language of quorum sensing is quite specific that allows precise communication even between the strains of bacterial species. Now, mechanisms that inhibit the quorum sensing have been elucidated across eukaryotic and prokaryotic species that enable them to fight against and interfere with the growth of their competitors. The competitors have evolved mechanisms to synthesize and release enzymes that can break down the auto inducers or compounds that might act as mimics to the auto-inducers thereby preventing quorum sensing within the other bacterial population and promoting their own growth.
Need to Break Quorum Sensing:
There has been growing incidences of antibiotic resistance among various pathogenic microbial strains. Scientists are alarmed about the rapid pace at which the pathogenic harmful microorganisms are able to modify or acquire the genetic changes required to bring about the antibiotic resistance capacity in them. Therefore, the need of the hour is to search for alternatives to the use of antibiotics. Accordingly, the researchers have focused their attention towards the development of approaches that specifically targets the infective ability of the pathogens like virulent factors that are necessary to infect and cause the diseased condition within the host body.
This approach has found tremendous acceptance as it provides several advantages of inhibiting pathogenic bacteria as compared to the existing methods that are majorly synthetic based. The most important thing is that there is least chance of resistance against it due to lack of selective pressure. Rasmussen and his colleagues have demonstrated that the knock out of quorum sensing genes yielded a less pathogenic mutant form of Pseudomonas aeruginosa further confirming the validity of the process.
Existing Bacterial Signaling Inhibitors:
The current focus is to search for the most appropriate forms of quorum sensing inhibitors that could combat the virulence factors of the pathogens resistant to multiple available drugs. Unfortunately, very few synthetic compounds against the bacterial auto-inducers met with due success in animal models or clinical trials and hence are not suitable for application in humans. Some inhibitors of fungal origin have been identified with similar anti-quorum sensing properties.
But they are majorly mycotoxins and there is significant concern with respect to the safety of the recipients. Some other chemical compounds like the halogenated forms of furanones have been in use but they are relatively unstable. In the last decade or so the scientific community has shifted its focus towards the identification of such inhibitory compounds from plant based natural extracts. Subsequently, it was found that compounds from garlic, chili and carrot possessed inhibitory activities against the auto-inducers and interfere with quorum sensing. More plant extracts are being tried out but the characterization and proper dosage formulations is a difficult task to perform under in vivo conditions. Moreover, the plant compounds being from a different origin might provide the bacteria with the selection pressure required to cause resistance against it.
The Quorum Sensing Strategy:
The Gram (-) bacteria mostly utilizes the signal of N-acylhomoserine lactone (AHL) to assess their population size. The luxR protein is mainly entrusted with the role of AHL recognition and downstream transcriptional activation of the target genes. The proteins of the luxI family are responsible for the catalysis of the last step of AHL production. The general strategy is that each cell produces AHL and when the population size increases so does the AHL concentration. A significant number of bacterial properties and behaviors are regulated by the AHLs.
Some of the most important types include secretion of proteins, cytotoxin, capsule and extracellular enzyme synthesis, conjugal plasmid transfer, formation of biofilms and motility. Some of the pathogenic forms of Salmonella, Klebsiella and E. coli express a homolog of luxR called sdiA that provides them with virulent functions. However, they do not produce AHLs which are recognized by the luxR. The quorum sensing in these species are unique from the point of view that they synthesize sdiA which is a potential receptor for AHL but no AHL synthase. The E. coli O157:H7 toxicity is formed when they get attached to the host intestines, the genes of attachment being directly activated through quorum sensing. It is not that the pathogenic bacteria can only synthesize auto-inducers. Infact many other microbial flora including some of the potential probiotic bacteria like the bifidobacteria, lactobacilli can produce such molecules. Auger et al. have shown that such probiotic strains produce a luxS homologue as also other auto inducing molecules.
The Probiotic Role:
The probiotic bacteria L. acidophilus interfere with the quorum sensing in E. coli O157 and controls the genes of pathogenicity, colonization and inhibit toxicity according to the work of Medellin-Pena et al. The AHL degradation capacity has been known for the strains of B. cereus. Similar abilities have been demonstrated by B. toyoi that partially explains its probiotic action. Lactobacilli strains showed growth inhibitory actions on various pathogenic bacteria via the production of fatty acids, hydrogen peroxide, bacteriocins and other molecules. Many of these molecules were found to exert anti-autoinducer activities. Some of the compounds are now characterized like the analysis of the organic acids synthesized by Lactobacillus strains has shown the presence of phenyl lactic acid.
The probiotics can be put to use in the effective inhibition of the signalling mechanism between the pathogenic microorganisms and prevent their virulent abilities.