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Targeting Bacterial Quorum Sensing with Mineral-Based Calibrin®-Z

Calibrin®-Z Text with bacteria in the background.

The reduction in antibiotic growth promoter use — due to changing consumer preferences and concern over antimicrobial-resistant pathogens — has required a new approach to managing enteric disease in poultry and livestock. Unlike conventional antibiotics which kill bacteria, the antivirulence approach targets bacterial virulence factors (e.g., quorum sensing) and aims at modifying pathogen behaviors to make them less harmful to the host. The likelihood for multi-drug-resistant bacteria is much less when using this method.

Bacteria Use Quorum Sensing to Communicate

Quorum sensing is one of the antivirulence targets that can be used to help manage bacterial disease. Quorum sensing is a communication system between bacterial cells that involves bacteria releasing biochemicals into the environment which accumulate until reaching a critical threshold concentration.1 When that concentration is reached, changes are triggered inside the bacteria that modify how the bacteria behave.

Quorum sensing controls many bacterial functions including bioluminescence and the release of toxins that damage host cells. Bioluminescence production was one of the first examples of quorum sensing described in bacteria. To learn more about the fascinating bioluminescent species Vibrio fischeri and quorum sensing, watch this TED-Ed video.

Quorum Quenching Disrupts Bacterial Toxin Production

Toxins produced by pathogenic bacteria (e.g., alpha-toxin and NetB toxin from Clostridium perfringens) cost animal protein producers billions of dollars each year. However, quorum-quenching products may be a practical method of reducing the negative production and health effects caused by these toxins. Quorum quenching is an approach that disrupts the quorum-sensing system of pathogenic bacteria, preventing cell-to-cell communication and the expression of quorum-sensing-controlled genes that produce toxins and other virulence factors.

Additionally, quorum-quenching products should reduce the chance of antibiotic resistance, since they are modifying bacteria behavior rather than killing them.

Calibrin®-Z has Quorum-Quenching Properties

The mineral-based biotoxin binder Calibrin-Z (available in select international markets) has demonstrated antivirulence attributes that neutralize quorum-sensing signal molecules to reduce the harmful effects of pathogenic bacteria.

A study in the Journal of Agricultural and Food Chemistry demonstrated that in vitro, Calibrin-Z separated out quorum-sensing molecules by adsorption or catalytically broke them down into small fragments. By reducing the concentration of quorum-sensing biochemicals, Calibrin-Z potentially disrupts the ability of pathogenic bacteria to produce toxins, since this function is controlled through quorum sensing.

When incubated with Vibrio harveyi, a bacterium that exhibits bioluminescence controlled via quorum signaling, Calibrin-Z reduced bacterial luminescence by 55% (from the area under the curve; Figure 1). The bacterial numbers were not affected (Figure 2), indicating the bioluminescence reduction was achieved through quorum quenching — interfering with quorum sensing — and not by killing bacteria.

 

Graph showing Luminescence Over Time of Various Doses.
Figure 1: Bacterial luminescence from a Vibrio harveyi culture treated with different concentrations of Calibrin-Z. Vibrio parahaemolyticus (Vp) was used as a non-luminescent negative control. At 10 mg/mL, Calibrin-Z reduced bacterial luminescence by 55% (area under the curve).

 

Graph showing Bacteria Count Over Time of Various Doses.
Figure 2: Treatment with different concentrations of Calibrin-Z did not affect the growth of Vibrio harveyi.

 

Quenching quorum-sensing molecules is just one of the techniques that can be employed to control pathogens using the antivirulence approach. This is an exciting field that offers animal protein producers effective alternatives to antibiotics for controlling pathogens and their toxins. Visit the Calibrin-Z page to learn more about its biotoxin-binding properties.

 

Reference

  1. Naik SP, Scholin J, Ching S, Chi F, Herpfer M. Quorum Sensing Disruption in Vibrio harveyi Bacteria by Clay Materials. J. Agric. Food Chem. 2018; 66:40-44.
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