October 29, 2018Microbiome
Staphylococcus infections cause tens of thousands of deaths worldwide each year. Methicillin-resistant Staphylococcus aureus, or MRSA, is familiar to many people as a cause of serious disease. Less well known is that S. aureus often can live in the nose or gut without causing any harm. However, if the skin barrier is broken, or the immune system compromised, these colonizing bacteria can cause serious infections. One strategy to prevent Staph infections is to eliminate S. aureus colonization. However, some decolonization strategies are controversial because they require considerable amounts of topical antibiotics and have limited success, partly because they target only the nose and bacteria quickly recolonized from the gut.
A new study published in Nature (10 October 2018), has demonstrated that a good bacterium commonly found in probiotic digestive supplements helps eliminate Staphylococcus aureus. The study unexpectedly found that Bacillus bacteria prevented S. aureus bacteria from growing in the gut and nose of healthy individuals. Then, using a mouse study model, the authors identified exactly how that happens.
The study recruited 200 volunteers in rural Thailand. The choice of this population was based on the assumption that they would not be as affected by food sterilization or antibiotics as people in highly developed urban areas. Based on the study design the authors first analyzed fecal samples from each of the study participants for bacteria correlated with the absence of S. aureus. Results showed 101 samples positive for Bacillus, primarily B. subtilis -- the type found mixed with other bacteria in many probiotic products. Bacillus bacteria form spores that can survive harsh environments and commonly are ingested naturally with vegetables, allowing them to temporarily grow in the intestine. The authors then sampled the same 200 people for S. aureus in the gut (25 positive) and nose (26 positive). Strikingly, no S. aureus were found in any of the samples where Bacillus were present.
Using a confirmatory mouse study, the authors discovered an S. aureus sensing system that must function for the bacteria to grow in the gut. Intriguingly, all of the more than 100 Bacillus isolates recovered from the human feces, efficiently inhibited that system. Then using chromatography and mass spectrometry techniques, the authors identified fengycins, a specific class of lipopeptides, molecules that are part peptide and part lipid, as the specific Bacillus substance that inhibited the S. aureus sensing system. Additional tests showed that fengycins had the same effect on several different strains of S. aureus -- including high-risk USA300 MRSA which causes most community-associated MRSA infections in the United States and is an increasingly common cause of healthcare-associated MRSA infections. To further validate their findings, the authors colonized the gut of mice with S. aureus and fed them B. subtilis spores to mimic probiotic intake. Results showed that probiotic Bacillus given every two days eliminated S. aureus in the guts of the mice. The same test using Bacillus where fengycin production had been removed, had no effect, and S. aureus grew as expected.
The authors next plan is to test whether a probiotic product that contains only B. subtilis can eliminate S. aureus in people. The plan is to enroll more Thai volunteers for the project with the ultimate goal to determine if a simple probiotic regimen can be used to reduce MRSA infection rates in hospitals.