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quorum sensing (QS) is a mechanism of gene regulation of a variety of physiological activities such as enhancing access to nutrients and favorable environmental niches, and responses against competing bacteria and environmental stresses
New insights on how probiotics could displace enteric pathogens
Introduction
Prokaryotes, microscopic single-celled organisms without a distinct nucleous (such as bacteria), represent the most significant component of biodiversity in our world. For millions of years, prokaryotic organisms have functioned as a vital selective force influencing the evolution of eukaryote organisms such as animals and plants whose bodies are made of cells containing a nucleous, and organelles enclosed by a plasma membrane. Astronishing numbers of microorganisms (bacteria, fungi, algae, protozoa and viruses) are found both inside and outside of human and animal bodies which are diverse and complex in nature.
The human genome contains around 20,000 genes whereas around 3.3 million non-redundant genes are found to be present in microbiome of gastrointestinal tract. More than 99% of these genes belongs to 1000 to 1150 different bacterial species representing diverse and complex gut microbiota.
Among these microorganisms, bacteria residing on the gastrointestinal tract (gut bacteria) of both humans and animals have and continue to be widely studied due to their roles on health and diseases through complex interactions with their hosts including humans and animals. Different factors including diets, antibiotics, method of delivery, newborn feeding, illness, stress, aging, husbandry, and host genetics have been found to affect on gut microbiota. Imbalances or changes in gut microbiota compositions (dysbiosis) due to any of these factors factors can lead to disorders and several diseases.
There has been significant advancements in microbiological and molecular technologies along with both sequencing technologies and computational methods which have broadened our understanding of bacteria composition, structure, and their various roles in health and diseases. It is now widely accepted that gut bacteria play a vital role in various physiological and metabolic activities of all food producing animals, hence, it is very important to maintain their homeostasis and health status. Growing evidence demonstrates gut bacteria can play the following roles:
- Stimulate intestinal development
- Produce substances used as a source of energy by intestinal cells
- Facilitate digestion and nutrient absorption
- Stimulate and/or modulate immune mechanisms, and
- Maintain a healthy status
Therefore, growing knowledge and understanding of gut bacteria homeostasis and biodiversity (normal versus abnormal bacterial profiles), along with interactions between bacterial species in the gut and their hosts, could help enhance health and performance of poultry and other food production animals. The potential benefits are particularly important as the poultry industry continues to develop disease prevention strategies that do not rely on the use of antibiotics, and continues to further efforts to ensure food safety while reducing the risk of antimicrobial resistance.
Quorum Sensing
Multiple studies have revealed that bacteria communicate with each other in response to fluctuations in cell-population density by releasing, sensing and responding to small diffusible signaling molecules (autoinducers). This communication known as quorum sensing (QS) is a mechanism of gene regulation of a variety of physiological activities such as enhancing access to nutrients and favorable environmental niches, and responses against competing bacteria and environmental stresses. In addition, QS can be a mechanism of competitive or cooperative signaling across bacteria species or between bacteria and their host.
Such activities include symbiosis, virulence, motility, antibiotic production, and biofilm formation (see Figure 1). QS occurs in most bacterial species, however, there are differences in how these chemical signals are made, detected and responded from species to species. In many species QS modulates virulence functions and is important for pathogenesis in several enteric diseases. Similarly, social insects like bees and ants use QS to communicate and determine a suitable place to build their nest.
Figure 1. Quorum sensing through production and diffusion of secreted signal molecules (autoinducers)
For bacteria to use QS constitutively, they must possess three characteristics:
- to secrete a signaling molecule, an autoinducer
- to detect the change in concentration of signaling molecules, and
- to regulate gene transcription as a response
QS signaling molecules are usually secreted at a low level by individual bacteria. At low cell density, the molecules may just diffuse away. At high cell density, the local concentration of signaling molecules may exceed its threshold level, and trigger changes in gene expressions. It is well known that probiotic bacteria (such as Lactobacillus spp.) can produce proteic substances (such as bacteriocins) that can inhibit growth or deactivate other bacteria through QS mechanisms. These bacteriocins can be antagonistic to colonization and replication of Salmonella spp.
A biofilm is a combined form of microorganisms (single or several species) associated with a surface and enclosed in a polymeric matrix. Biofilms can grow on many different surfaces such as drinking water pipe lines at farms and hatcheries (see Figure 2). If biofilms are not removed, they can form permanent structures. As soon as the biofilm develops, the bacteria involved start to alter their gene structure by releasing chemicals as a result of changes in population density. This QS mechanism allows biofilms to grow and develop synergistic functions that promote survival. Within a biofilm, bacteria can share nutrients and be sheltered from harmful factors in the environment, such as desiccation, chemicals, and the animals’ immune system. Furthermore, bacteria present in biofilms develop into non-dividing or slow-growing persistent colonies that are insensitive to the action of antimicrobial drugs, can develop resistance, and function as a reservoir of pathogenic bacteria and persistent infections.
Figure 2. Biofilms formed by microorganisms adhered to the surface of water pipe lines
Interkingdom communication: communication between bacteria and hosts
Communication/signaling between bacteria and hosts is known as interkingdom communication. Previously, QS was believed to occur only among bacteria, but later on, several studies reported the existence of cross communication between bacterial and host signaling system. The cross talk between bacteria and hosts involves hormones produced by host and AI produced by bacteria. For example, adrenaline and nor adrenaline secreted by the host cells are sensed by bacterial membrane receptors leading to increase in virulence and pathogenicity of entero pathogens such as Salmonella, Campylogacter and E. coli.. On the other hand, gastrin, which is a hormone secreted by stomach cells that stimulate secretion of gastric acid, has been associated with increase in the growth of H. pylori. Furhtermore, bacteria can sense different components of immune system such as, cytokines, and antimicrobial peptides that modulate the host immune responses.
Animals, plants, fungi, virus and bacteria produce extracellular nanovescicles that contain MicroRNAs (miRNAs) and other molecules that they use to communicate among them. This inter kingdom crosstalk has been demonstrated between humans, farm animals, bacteria, virus, fungi and plants. The importance of the gut microbiota is enormous since an imbalance within the microbial composition may lead an individual to shift from physiological symbiosis to a dysbiosis and, ultimately, from health to disease. In the perinatal period, gut microbiota can be affected by several factors such as the mode of delivery, bacterial infections, antibiotic treatments, and lifestyle. Once established, gut microbiota can be altered through eating habits and diet. In recent years, a new paradigm has evolved as nutrition research has moved from classical epidemiology and physiology to molecular biology and genetics.
Interactions between probiotics and their roles in maintaining microbial homoestasis
Complex microbial interactions through their communication systems which help to communicate between themselves or with hosts help them to maintain their niches and host homoestasis. Microbial interactions can be either mutualistic or antagonistic and thus either they co-operate each other through horizontal gene transfer, biofilm formation, or compete for nutrients and combat with other species or pathogens through expression of bacteriocins, microcins, and colicins.
Recent studies on QS indicate that bacterial communication can be used as alternative to antibiotics.
The discovery of new QS molecules have proved to be useful in the treatment of diseases for which conventional options do not work. The production of safe foods, free of pathogens, has been receiving increasing attention due to market demands for food products of high quality and free of residues. A recent study demostrated that the production of AI from Lactobacillus plantarum obtained during the in vitro inhibition of Salmonella Heidelberg (SH), improve positively the communication with the normal microbiota and inhibiting SH in newborn chicks. In addition, the microRNAs (miRNAs) have been shown to play important roles in the development of the immune system and in regulation of host inflammation responses. Probiotics can effectively alleviate the inflammation caused by Salmonella in chickens.
Next to the potential antimicrobial functionality, quorum sensing derived molecules, especially the peptides, are being investigated for their use in other therapeutic domains as well, including immunology, central nervous system disorders and oncology. Therefore, recent discoveries and understanding of molecular mechanisms of cross and inter-species communication such as QS will help develop new approaches and alternatives to control bacterial infections in food producing animals.