How NOT to Stop Bacterial Biofilms

Most bacteria have at their disposal a smart strategy to escape environmental chemical and physical stresses by forming fortress around themselves known as biofilms. Bacterial biofilm consists of a complex mixture of biopolymers including proteins and DNA. While biofilms are beneficial to bacteria, they are a big problem for public health. For example, bacterial biofilms frequently develop on surgical implants, which may lead to deteriorating performance and further complications. Over 80 percent of all incidences of microbial infections are related to biofilms. Biofilm–associated bacterial cells are inherently more tolerant to antibiotic treatment and can lie dormant to resist the actions of the antibiotics. The development of drugs that can disrupt biofilm formation and disperse existing biofilm is of prime importance.

Recently, this research area was invigorated by the supposed demonstration that unnatural D-amino acids (similar to amino acids that make up our proteins but they point in the opposite direction in space) can stop the formation of biofilms and disperse existing biofilms. This research group reported in the journal Science in 2010 that D-amino acids prevented the formation of biofilm in a number of disease-causing bacteria, including B. subtilis, S. aureus, and P. aeruginosa. The potentially promising anti-biofilm activities for D-amino acids led us to investigate a large series of unnatural D-amino acids in search of more potent D-amino acid agents. We had hypothesized that by exploring a large and diverse set of D-amino acids, we would discover drugs that effectively stopped bacterial biofilm. We purchased a large library of D-amino acids and set out to systematically test them (this work was supported by a Lehigh University Faculty Innovation Grant). Instead, we found that, contrary to published reports, none of the unnatural D-amino acids (including the same ones that were published) we evaluated displayed inhibition of biofilm formation against strains of B. subtilis, S. epidermis, and S. aureus at even high concentrations of D-amino acids.

After discussing with several colleagues in field, we decided to publish our findings that contradict the original report. We published our work in the journal Plos ONE. Since the publication, I have received tens of e-mails from researchers all across the world thanking us for clearing up the literature. They too had found that the original results were unreproducible.

There is a good ending to this story. After we learned that this was not a viable strategy to stop bacterial biofilms, we switched directions to an area that is working out extremely well. We will have a blog entry at a later date detailing our research progress in this area.

This guest post was contributed by Dr. Marcos Pires.  Dr. Pires is an assistant professor in the Department of Chemistry at Lehigh University.  His research interests include protein oligomerization, biomaterials, and multidrug resistance.  He is the recipient of a 2014 Faculty Innovation Grant.

Leave a Reply