MedicalResearch.com Interview with:
Christopher M. Waters PhD
Departments of Microbiology and Molecular Genetics
BEACON Center for The Study of Evolution in Actio
Michigan State University
East Lansing, MI
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Our research really centers on understanding and targeting bacterial biofilms. These are multicellular communities of bacteria encased in a slimy matrix that protects them from the immune system and antibiotic treatment during infections. One of the most common types of biofilm infections is in the lungs of cystic fibrosis by the bacterium Pseudomonas aeruginosa. CF patients can become chronically colonized by P. aeruginosa, and antibiotics are not able to clear these infections.
Our idea was can we find other molecules that make antibiotics more effective at killing biofilms? To this end, we screened about 6,000 compounds for those that would make tobramycin more effective at killing P. aeruginosa biofilms, and one of the best hits we found was the antimicrobial triclosan that has been widely used for decades in hand sanitizers, soaps, and tooth paste. Although neither triclosan nor tobramycin can kill biofilms alone, the combination is 100X more effective against virtually every P. aeruginosa strain tested. It also worked against other bacteria that commonly infect cystic fibrosis lungs such as Staphylococcus aureus and Burkholderia cenocepacia.
MedicalResearch.com: What should readers take away from your report?
Response: Since triclosan has been widely used and is FDA approved to be used in toothpastes at very high concentrations, we think that there is a viable path forward to combining this with tobramycin to treat bacterial biofilms. This treatment can help cystic fibrosis patients, but also potentially other biofilm-based infections such as diabetic non-healing wounds or contamination of artificial implants such as hips, knees, and catheters. Unfortunately, right now there are not effective approaches to eliminate these infections as antibiotics have such little activity against bacterial biofilms.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We are currently working hard to do the preclinical studies necessary to approach the FDA about clinical trials. This involves getting more animal efficacy results and further testing the safety of the combination. Although there have been hundreds of studies showing triclosan is well tolerated, delivering it to the lungs would be a new indication and we need to ensure that it is safe. To this end, we have already done preliminary studies at MSU that show little toxicity of triclosan in the lungs.
MedicalResearch.com: Is there anything else you would like to add?
Response: Combating antibiotic-resistant infections will take a multi-pronged approach. We think that this approach of identifying small molecules that enhance antibiotic activity, so called “antibiotic-adjuvants”, is one way that we can empower the preexisting antibiotic arsenal. Triclosan is just the tip of the iceberg. We have other combinations in development, and we would like to increase the number of compounds we screen from 6,000 to the hundreds of thousands.
Michael M. Maiden, Alessandra M. Agostinho Hunt, Mitchell P. Zachos, Jacob A. Gibson, Martin E. Hurwitz, Martha H. Mulks, Christopher M. Waters. Triclosan is an aminoglycoside adjuvant for the eradication of Pseudomonas aeruginosa biofilms. Antimicrobial Agents and Chemotherapy, 2018; AAC.00146-18 DOI: 10.1128/AAC.00146-18
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