Elimination of Pathogens by Signaling Interference

By Allan Mai ‘20

probiotic.jpeg

Figure 1. A new study has unveiled the complex molecular mechanism by which probiotics combat S. aureus colonization and infections alike.

Ever see that probiotic label on the side of a container of yogurt or another dairy product and wonder what it means? Probiotic nutrition helps reduce pathogenic colonization of the intestines; however, until recently, researchers’ knowledge of the mechanism behind this process was ambiguous. Pipat Piewngam of Mahidol University in Thailand and his colleagues have discovered that the probiotic Bacillus works by blocking the pathogen’s signaling system. Their study details a complex molecular mechanism and explains how this mechanism can be used to combat S. aureus colonization and infections alike.

Approximately 12.5 and 13 percent of the sample population in the study carried S. aureus in their intestines and nasal fluid, respectively. Researchers found a correlation between the presence of Bacillius and the absence of S. aureus. When Bacillius was present in fecal samples that normally contain S. aureus, the latter was not detected. The team first hypothesized that the Bacillius bacteria was secreting some sort of growth-inhibitory substance that was preventing the development of colonies in S. aureus. However, this premise was later disproved when there was minor growth inhibition in only six of the 105 isolates studied. The researchers then suspected the inhibition by quorum sensing, which is the ability for bacteria to sense the density of a colony and make appropriate alterations to the cell physiology. Having used a mouse model to test whether quorum sensing is crucial for bacterial colony formation in S. aureus, Piewngam and his team determined that without this phenomenon, colonies would be able to form.

After a series of trial and error experimentation, the researchers found that the mechanism for quorum inhibition actually competitive inhibition of Agr, an autoinducing peptide that is part of the signal-transduction system in S. aureus. Bacillius produces a substance known as fengycin, which is the main competitor of Agr in the binding site of the signal transduction system. By effectively blocking out this crucial peptide, fengycin ensures that colonization is not be achieved.These findings have many translational implications. For starters, they offer alternative ways to combat antibiotic-resistant S. aureus species, which are increasingly more abundant. Second, while current antibiotic approaches only decolonize the nasal cavity, this method offers a way to decolonize bacterial species in both the nose and the intestines.

 

References

  1. P. Piewngam, et. al., Pathogen elimination by probiotic Bacillus via signalling interference. Nature (2018). doi: https://doi.org/10.1038/s41586-018-0616-y  
  2. Image retrieved from: https://www.pexels.com/photo/clear-glass-hermetic-jar-209460/
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