The Need

Pseudomonas aeruginosa, a biofilm-producing pathogenic bacterium, exhibits resistance to many antibiotics. This leads to acute and chronic joint infections that are difficult to treat. Accordingly, a critical need exists for accurate biofilm diagnosis, prevention, and treatment. While culture-free immunological markers are used for diagnostics, they do not identify specific bacterial pathogens and can be produced from various conditions.

P. aeruginosa can lead to periprosthetic joint infection (PJI). PJI is a devastating complication of joint replacement surgery requiring multiple surgeries and often resulting in amputation. PJI is difficult to diagnose due to a high rate of false negatives by time-consuming clinical culturing methods. PJI symptoms are also like symptoms from other non-infectious causes. Without simple diagnostics, early treatments and pathogen-specific interventions are unfeasible. Antibiotics are often prescribed anecdotally and furthermore tend to be ineffective.

The Technology

Researchers at The Ohio State University, led by Dr. Paul Stoodley and Dr. Rafael Bruschweiler, have identified specific metabolites and unique metabolite signatures produced by bacteria grown as biofilms using nuclear magnetic resonance (NMR)-based metabolomics.

Specifically, they have found metabolite differences among two common pathogens, P. aeruginosa and Staphylococcus aureus, in bovine synovial fluid as well as human joint fluid. These findings show the potential of NMR-based metabolomics as a tool for diagnosis and identification of new targets for prevention and control of biofilm-related joint infections.

The identification of metabolic differences between P. aeruginosa planktonic and biofilm phenotypes led to the discovery that the cadaverine branch of the lysine degradation pathway is linked to the establishment of the growth mode in P. aeruginosa. Moreover, cadaverine is a potential target for prevention and mitigation of P. aeruginosa biofilm infections. These findings also support interventional strategies to control such biofilm formation.

Commercial Applications

• Identification of bacterial biofilms to develop treatments for acute and chronic joint infections
• Detection of species-specific diagnostic metabolites of PJI using synovial fluid during an office visit
• Monitor treatment efficacy over time

Competitive Advantages/Key Benefits

• Some metabolites are specific to bacteria and not produced by humans
• Metabolites can distinguish between different strains of bacteria
• Metabolite signatures can identify bacterial biofilms
• Culture-free diagnostic approach
• Broad application - many chronic infections have biofilm involvement

Patent

Metabolite based diagnostics for periprosthetic joint infection, patent pending.

Publications

• Leggett, A. et al. Cadaverine Is a Switch in the Lysine Degradation Pathway in Pseudomonas aeruginosa Biofilm Identified by Untargeted Metabolomics. (2022). Frontiers in Cellular and Infection Microbiology, 12:833269.
• Leggett, A. et al. Differential metabolism between biofilm and suspended Pseudomonas aeruginosa cultures in bovine synovial fluid by 2D NMR-based metabolomics. (2022). Scientific Reports, 12:17317.