Understanding how bacterial communication results in virulence is providing new insights into animal gut health and disease, insights that today’s feed industry can leverage now.
The risk of disease is a fact of life for farmers, ranchers and food animal producers whether they are raising crops, pigs, poultry, fish or shrimp. Disease results from a pathophysiologic process that involves not only the pathogen (e.g. bacterium, virus or fungus) but also the host’s microbiota and immune response. At the root of enteric infections is an imbalance in the intestinal immune-microbiota axis. Consequently, the complex interactions between feed, microbiome and host immune system have emerged as a primary focus for devising new strategies to combat livestock intestinal health issues.
Not merely “passengers”
The gut microbiota is actively involved in host immunity and physiology. Dominated by bacteria, the composition of the intestinal microbiota is dynamic and diverse in both populations and densities along the different parts of the gastrointestinal tract (GIT).
The “normal” microbiota includes both commensal and disease-causing bacteria.
The host animal reaps health benefits from the intestinal microbiota, such as:
- helping with feed digestion
- nutrient synthesis
- intestinal barrier maintenance
- immune system function
- inhibition of harmful bacterial species.
However, intestinal bacteria can cost the host animal through:
- competition for nutrients,
- stimulation of rapid enterocyte turnover,
- toxin secretion
- induction of gastrointestinal inflammation.
The gut microbiota plays a central role in protecting an animal from enteric bacterial infection. But many intestinal pathogens have developed strategies to outcompete the intestinal community, leading to infection and disease. One way pathogenic bacteria thwart the gut microbiota is by using alternative nutrients, such as microbiota-derived sources of carbon and nitrogen. They also exploit regulatory signals from the microbiota and the host to promote their own growth and virulence. This signalling among bacteria is referred to as quorum sensing (QS).
The gut microbiota plays a central role in protecting an animal from enteric bacterial infection. Photo: Dreamstime
What is quorum sensing?
Bacteria “talk” to each other using chemicals as their words, a signalling system now known as quorum sensing. Numerous bacterial species make small-molecule signals, called autoinducers (AI), that they release into their immediate environment to track changes in cell numbers. As the bacterial population grows, increasing in density, AI concentrations also accumulate. When AI levels reach threshold, a series of events are triggered inside bacteria that ultimately result in changing the bacterial population’s behaviour and enable it to act as a large multicellular organism.
2 important behaviours governed by QS are:
- antibiotic resistance
- virulence expression.
Rather than individual bacterial cells expressing virulence factors, QS enables bacterial populations to achieve a population large enough for virulence factor expression, such as the production of extracellular toxins that damage the intestinal wall, reduce productivity and cause clinical disease. Most QS systems promote communication between bacteria of the same species (intraspecies communication), with gram-positive and gram-negative bacteria using different systems to talk among themselves. However, many bacteria have a second QS system that is thought to enable communication between different bacterial genera (interspecies communication). More recently, bacterial communication has been shown to cross kingdom boundaries with the recognition that some bacteria sense host signalling chemicals such as the hormones adrenaline and noradrenaline.
Potential promise of QS
The connection between QS and pathogenic bacterial virulence generated excitement for a potentially new approach to fighting bacterial infections, targeting and disrupting QS. Many bacterial species relevant to livestock production and veterinary medicine, including those mentioned previously, use QS to regulate production of virulence factors that are essential for bacterial infection. Preventing bacteria from producing virulence factors could be an important alternative strategy, known as antivirulence therapy, for combating bacterial diseases. An antivirulence paradigm focuses on disarming bacteria by preventing virulence factor production or by neutralising those factors. Scientists have identified three routes by which to interfere with QS systems as part of an antivirulence strategy: Inhibit the making of QS signal molecules, inhibit the interaction between a QS signal molecule and its related receptor and quench extracellular QS signal molecules through neutralisation or degradation.
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Promoting intestinal health
Interfering with or blocking QS does not kill pathogenic bacteria but instead inhibits virulence factor production, and has been suggested to apply less selection pressure that could result in antimicrobial resistance than conventional antibiotics.
Technology that leverages QS disruption is currently available to today’s livestock and poultry industries. Recent in vitro research conducted by Amlan International demonstrated that their unique activated mineral can function not only as an adsorbent to quench QS signal molecules but also as a catalyst that mediates degradation of these molecules. This mineral technology serves as the technical base for the company’s formulated feed additives that promote intestinal health and animal growth.
In the first phase of the study, researchers evaluated the ability of 5 different clay minerals to remove a QS signal molecule, N-(3-oxooctanoyl)-DL-homoserine lactone, at different concentrations and temperatures. Certain materials, due to their surface properties and porosity, catalytically degraded the QS molecule into smaller fragments. Depending on their concentration, some of the materials functioned as adsorbents and others as catalysts that cause and accelerate the break down of QS signal molecules.
In the second phase of the study, 2 methods were used to monitor luminescence and population density of bacteria, where quenching of bacterial QS activity was observed by means of luminescence reduction. The results found that specifically processed or activated minerals can be used as catalysts to disrupt bacterial activity in various media. In method one, an activated calcium montmorillonite (Calibrin®-Z, Amlan International) reduced bacterial luminescence by 55% at a 10 mg/mL concentration without affecting bacterial numbers. In method two, activated calcium montmorillonite caused a delay in luminescence by selectively interfering with QS.
The future is already here
At a time when producers are looking for antibiotic alternatives to help maintain the health of their herds and flocks, feed additives that work by disrupting QS are a valuable tool for promoting animal health and nutrition. Although more research is needed to better understand different species’ gut health, QS disruption is an antivirulence strategy that holds promise for minimising the effects of enteric bacterial diseases, preserving intestinal integrity and promoting livestock performance in antibiotic-free production systems.
References are available upon request.