Medical Student University of Central Florida College of Medicine, Florida, United States
Matthew Caldwell (University of Central Florida)| Melanie Coathup (University of Central Florida)
Background: The CDC reported that over 719,000 total knee and 332,000 total hip replacements were performed in the United States in 2010, and this number continues to rise. Implant infection is reported in up to 5% of these cases, leading to weeks of antibiotics, surgical revisions, and pain or death. Various bacteria contribute to these infections, most commonly including Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa, with a majority of these bacteria possessing the innate ability to form a biofilm. Biofilm is formed of bacteria, proteins, extracellular polymeric substances, eDNA, and various other compounds, with the goals of protection and adhesion to surfaces. These biofilms can be polymicrobial, confer antibiotic resistance, protect against host immune responses, and are inherently difficult to treat once established. Because of this, new options are needed to detect, disperse, and inhibit bacterial adhesion and biofilm formation on orthopaedic implant surfaces. D-amino acids (DAAs) are a promising solution. DAAs are isomers of L-amino acids used to build proteins, with prokaryotes utilizing DAAs to form peptidoglycan, confer morphology, protect against proteases, and act as antimicrobials during interspecies competition. Additionally, DAAs have been shown to inhibit or disperse biofilms in many of the most common implant pathogens in vitro through disruption of cell-to-cell adhesion and cell wall polymerization. Because DAAs are much less common in eukaryotes, these essential components of bacteria are a prime target for exploitation. This study focused on exploring the hypothesis that through inhibiting cell-to-cell adhesion and cell wall polymerization, these molecules are able to inhibit biofilm formation on an implant surface. We have also hypothesized that DAAs may offer a novel method of detecting bacterial growth through both radio-labeled DAAs (RDAAs) and fluorescent DAAs (FDAAs).
Methods: Using Pubmed, Google Scholar, and web of science, a search of the published literature was carried out. Over 30 articles from the last decade pertaining directly to the uses and roles of D-amino acids were examined based on (i) their antimicrobial activity, (ii) their ability to inhibit or disperse biofilm and, (iii) their success in detecting infection.
Results: (i) D-tyrosine, D-tryptophan, and D-phenylalanine showed an inhibitory effect on the progression and maturation of biofilms across widest array of species, and when combined with antibiotics, these effects become more potent. (ii) The concentrations of DAAs required to affect biofilms negatively are much lower than the concentrations shown to be toxic to osteoblasts and fibroblasts in vitro. (iii) FDAAs have come to market that detect peptidoglycan formation in real-time, alongside RDAAs that have been utilized to detect active infection in mice. FDAAs coated onto an implant would allow visualization of bacterial growth before surgery is performed, and RDAAs would allow visualization of infection once inside the body.
Conclusion: The anti-microbial and anti-biofilm nature of DAAs, low toxicity to osteoblasts and fibroblasts, and newly developed detection strategies highlight the potential use of these molecules in orthopaedics, and necessitate exploration moving forward.