“Nothing to see here, move along.” Like a police officer dispersing a crowd before it can run riot, a small peptide can interfere with the formation and maintenance of biofilms, structured communities of identical bacteria. The peptide, known as 1018, consists of just 12 amino acids, but it has been shown to have outsized effects. In a study conducted by researchers at the University of British Columbia (UBC), 1018 prevented biofilm formation and eradicated mature biofilms in both gram-negative and gram-positive bacteria, including the major resistant pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and methicillin-resistant Staphylococcus aureus (or MRSA).
At doses that did not affect the planktonic growth of free-swimming bacteria, the peptide dispersed biofilms; at higher doses, the peptide triggered biofilm cell death.
These results were published May 22 in PLOS Pathogens, in an article entitled “Broad-Spectrum Antibiofilm Peptide That Targets a Cellular Stress Response.” The article outlines how the BSU researchers explored 1018’s mechanism of action.
The researchers, led by Bob Hancock, Ph.D., reasoned that 1018 had to interfere with a process that is common to different bacterial species. One such process is the widespread “stringent stress response” that uses specific mediators called (p)ppGpp to orchestrate the expression of a plethora of genes that help bacteria to cope with changing environments. The scientists hypothesized that 1018 (and possibly other antibiofilm factors) acted by blocking the stringent response.
They went on to test this idea by overproducing the mediator (p)ppGpp in biofilm-forming bacteria, and the fact that this made the bacteria more resistant to 1018 suggested that they were on the right track. They then went on to demonstrate that 1018 directly and specifically interacts with (p)ppGpp, triggers the destruction of the mediator, and thereby prevents its role in biofilm formation and maintenance.
The researchers conclude that “the strategy presented here represents a significant advance in the search for new agents that specifically target bacterial biofilms.” On this basis, they are working to “take advantage of the opportunity to now develop more active peptides that have even more potent antibiofilm activity.”
The findings uncovered by the BSU researchers are encouraging because at present there are no approved treatments for biofilm infections. In addition, bacteria in biofilms are considerably more resistant to standard antibiotics. Yet, if biofilm-dispersing strategies prove to be effective, they may lessen the threat of antibiotic resistance. Many bacteria that grow on skin, lung, heart, and other human tissue surfaces form biofilms, which cause two thirds of all infections and demonstrate a 10 to 1000 fold increase in adaptive resistance to conventional antibiotics.