Quorum sensing (QS) refers to the capacity of bacteria to monitor their population density and regulate gene expression accordingly: the QS-regulated processes deal with multicellular behaviors (e.g. growth and development of biofilm), horizontal gene transfer and host-microbe (symbiosis and pathogenesis) and microbe-microbe interactions. QS signaling requires the synthesis, exchange and perception of bacterial compounds, called autoinducers or QS signals (e.g. N-acylhomoserine lactones). The disruption of QS signaling, also termed quorum quenching (QQ), encompasses very diverse phenomena and mechanisms which are presented and discussed in this review. First, we surveyed the QS-signal diversity and QS-associated responses for a better understanding of the targets of the QQ phenomena that organisms have naturally evolved and are currently actively investigated in applied perspectives. Next the mechanisms, targets and molecular actors associated with QS interference are presented, with a special emphasis on the description of natural QQ enzymes and chemicals acting as QS inhibitors. Selected QQ paradigms are detailed to exemplify the mechanisms and biological roles of QS inhibition in microbe-microbe and host-microbe interactions. Finally, some QQ strategies are presented as promising tools in different fields such as medicine, aquaculture, crop production and anti-biofouling area.

Quorum quenching: role in nature and applied developments.

Nisin is a bacteriocin produced by a group of Gram-positive bacteria that belongs to Lactococcus and Streptococcus species. Nisin is classified as a Type A (I) lantibiotic that is synthesized from mRNA and the translated peptide contains several unusual amino acids due to post-translational modifications. Over the past few decades, nisin has been used widely as a food biopreservative. Since then, many natural and genetically modified variants of nisin have been identified and studied for their unique antimicrobial properties. Nisin is FDA approved and generally regarded as a safe peptide with recognized potential for clinical use. Over the past two decades the application of nisin has been extended to biomedical fields. Studies have reported that nisin can prevent the growth of drug-resistant bacterial strains, such as methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Enterococci and Clostridium difficile. Nisin has now been shown to have antimicrobial activity against both Gram-positive and Gram-negative disease-associated pathogens. Nisin has been reported to have anti-biofilm properties and can work synergistically in combination with conventional therapeutic drugs. In addition, like host-defence peptides, nisin may activate the adaptive immune response and have an immunomodulatory role. Increasing evidence indicates that nisin can influence the growth of tumours and exhibit selective cytotoxicity towards cancer cells. Collectively, the application of nisin has advanced beyond its role as a food biopreservative. Thus, this review will describe and compare studies on nisin and provide insight into its future biomedical applications.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jam.13033

Biomedical applications of nisin

Functions and emerging applications of bacteriocins.

The interest on novel biological preservation methods has been increasing during recent years, supported by research indicating that antagonistic microorganisms and their antimicrobial metabolites may have some potential use as natural preservatives as a way not only to control the growth but also to inactivate undesired microorganisms in food. Biopreservation using lactic acid bacteria (LAB) and/or their antimicrobial metabolites represents an alternative for improving food safety. These antimicrobial properties of LAB were derived from competition for nutrients and the production of one or more antimicrobial active metabolites such as organic acids (mainly lactic and acetic acid), hydrogen peroxide and also other compounds, such as bacteriocins and antifungal peptides. The important contribution of probiotic LAB in food preservation has been attracting much attention because of the nutritional qualities of the raw material through an extended shelf life of food and their ability to inhibit spoilage and foodborne pathogens, which is interesting for the food industry. In this review, we compiled the available data on the commonly used preservative and present the current knowledge regarding the antimicrobial compounds, especially bacteriocins, the mechanisms of the action and recent applications of antimicrobial compounds in food. The use of competitive microbiota as a biotechnological tool for food preservation may lead to improve the optimization and quality assurance of food products while at the same time retaining the sensory qualities of the product such as color, flavor, texture and nutritional value.

Lactic Acid Bacteria Antimicrobial Compounds: Characteristics and Applications

Resistance to antibiotics is escalating and threatening humans and animals worldwide. Different countries have legislated or promoted the ban of antibiotics as growth promoters in livestock and aquaculture to reduce this phenomenon. Therefore, to improve animal growth and reproduction performance and to control multiple bacterial infections, there is a potential to use probiotics as non-antibiotic growth promoters. Lactic acid bacteria (LAB) offer various advantages as potential probiotics and can be considered as alternatives to antibiotics during food-animal production. LAB are safe microorganisms with abilities to produce different inhibitory compounds such as bacteriocins, organic acids as lactic acid, hydrogen peroxide, diacetyl, and carbon dioxide. LAB can inhibit harmful microorganisms with their arsenal, or through competitive exclusion mechanism based on competition for binding sites and nutrients. LAB endowed with specific enzymatic functions (amylase, protease…) can improve nutrients acquisition as well as animal immune system stimulation. This review aimed at underlining the benefits and inputs from LAB as potential alternatives to antibiotics in poultry, pigs, ruminants, and aquaculture production.

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Benefits and Inputs From Lactic Acid Bacteria and Their Bacteriocins as Alternatives to Antibiotic Growth Promoters During Food-Animal Production.

Biofilm-associated bacteria are less sensitive to antibiotics than free-living (planktonic) cells. Furthermore, with variations in the concentration of antibiotics throughout a biofilm, microbial cells are often exposed to levels below inhibitory concentrations and may develop resistance. This, as well as the irresponsible use of antibiotics, leads to the selection of pathogens that are difficult to eradicate. The Centers for Disease Control and Prevention use the terms "antibiotic" and "antimicrobial agent" interchangeably. However, a clear distinction between these two terms is required for the purpose of this assessment. Therefore, we define "antibiotics" as pharmaceutically formulated and medically administered substances and "antimicrobials" as a broad category of substances which are not regulated as drugs. This comprehensive minireview evaluates the effect of natural antimicrobials on pathogens in biofilms when used instead of, or in combination with, commonly prescribed antibiotics.

Control of Biofilm Formation: Antibiotics and Beyond

Bacteriocins and their position in the next wave of conventional antibiotics.

Publisher Summary Quorum sensing was commonly referred to as autoinduction. Autoinduction was originally described for the Gram-negative marine organism Vibrio fischeri in early 1970s. The series of experiments conducted by Kempner and Hanson (1968) revealed induction of bioluminescence in freshly inoculated V. fischeri. There is no doubt that the practical applications of quorum-sensing research carry enormous potential; however, it is crucial to realize that the direction of scientific exploration has always been influenced by the opinions of the scientific community. There are numerous examples in the history of science of appealing yet inaccurate functional theories that directed research onto a path of ambiguity. The attempt to utilize the relatively simple AI-2 detection assay initiated numerous questions, which led to uncover conflicting theories in every major aspect of quorum-sensing research. The very function of quorum sensing is not completely clear. The evolution of this process in bacteria could possibly have been driven by the need to sense the flow dynamics of their immediate environment, as opposed to the need for a concerted response. Since multiple factors could influence the direction of development in evolution, both theories could be correct and therefore have a right for coexistence. Conversely, the theory of AI-2-mediated interspecies communication seems likely to remain weak or even fall apart from insufficient supportive results.

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Quorum sensing: fact, fiction, and everything in between.

Aims: To test e-poly-l-lysine and nisin A for possible synergistic activity against selected food-borne pathogens and food spoilage organisms.



Methods and Results: Synergistic activity was observed against Gram-positive Listeria monocytogenes and Bacillus cereus cells and spores of B. cereus in 96 well plate assays. However, nisin A had no effect alone or in combination with e-poly-l-lysine against Gram-negative Escherichia coli cells. In addition, when tested against yeast Zygosaccharomyces bailii, nisin A and partially inhibitory concentrations of e-poly-l-lysine antagonized each other.



Conclusions: Nisin A and e-poly-l-lysine showed synergistic activity against B. cereus and L. monocytogenes.



Significance and Impact of the Study: The application of nisin A and e-poly-l-lysine is a promising all-natural method of controlling Gram-positive food-borne pathogens, spores and spoilage organisms.

https://sfamjournals.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1472-765X.2007.02157.x

-Poly-L-lysine and nisin A act synergistically against Gram-positive food-borne pathogens Bacillus cereus and Listeria monocytogenes

The present study aims to examine the efficacy of the natural antimicrobial e-poly-l-lysine against Streptococcus mutans and against total aerobic oral microflora, alone and in combination with the natural antimicrobial peptide nisin. In in vitro studies, natural antimicrobials nisin A and e-poly-l-lysine synergized in their action against S. mutans, leading to the microorganism’s full inhibition, while having a less inhibitory effect on total aerobic oral microbiota.

Dimitri Kashtanov

Papers

Control of Biofilm Formation: Antibiotics and Beyond

Bacteriocins and their position in the next wave of conventional antibiotics.

Quorum sensing: fact, fiction, and everything in between.

-Poly-L-lysine and nisin A act synergistically against Gram-positive food-borne pathogens Bacillus cereus and Listeria monocytogenes

Natural Antimicrobials ε-Poly-l-lysine and Nisin A for Control of Oral Microflora