BACKGROUND
Bacterial resistance to antibiotics is a serious worldwide health problem, presenting the risks of increased infection and uncontrolled transmission. Unfortunately, established antibiotic treatments can be ineffective against resistant bacterial strains, consequentially increasing mortality rates, healthcare expenditures, and hospital resources. Caused by Pseudomonas species, multi-drug resistant P. aeruginosa infection has increased prevalence in immunocompromised, diabetic, and ventilated patients. The Centers for Disease Control (CDC) reports that (pre-pandemic) over 6,000 annual antibiotic resistant P. aeruginosa infections occur in healthcare settings in the United States, representing 13% of total U.S. P. aeruginosa infections. P. aeruginosa results in high hospitalization rates and causes over 400 annual deaths in the United States alone, and is thus classified as a serious threat level by the CDC. The increased use of ventilators due to the SARS-Cov2 pandemic corresponds to a spike in ventilator-related pneumonia, which is commonly caused by Pseudomonas infection. There is a critical need for developing novel treatments of resistant Pseudomonas and other resistant microbes.
SUMMARY OF TECHNOLOGY
OSU researchers have developed a novel therapeutic approach for the treatment of multi-drug resistant Pseudomonas infections. This approach exploits the properties of P. aeruginosa strains that are deficient for a recombinase enzyme called XerC. These strains display increased production of pyocins (P. aeruginosa-killing protein complexes) and simultaneously show hypersensitivity to fluoroquinolone antibiotics such as ciprofloxacin. Current experimental data show that antibiotic-mediated cell killing can be synergistically enhanced by combining XerC deficiency in P. aeruginosa with fluoroquinolone antibiotics. The invention further discloses the method for inducing pyocin production, rendering P. aeruginosa strains more vulnerable to standard antibiotic treatment, thereby reducing the concentration of antibiotic necessary to prohibit P. aeruginosa growth. The ultimate goal is to develop chemical inhibitors of XerC that induce the same antibiotic sensitivity and pyocin production as seen in genetically deficient ΔxerC strains. A screening method for such chemical inhibitors is disclosed.
POTENTIAL AREAS OF APPLICATION
- A novel treatment for multi-drug resistant P. aeruginosa infections
- Reduce side effects by lowering antibiotic effective doses in the treatment of P. aeruginosa infections
- Extend the effect of antibiotic treatment through pyocin-mediated killing of P. aeruginosa
- A screening assay for discovery of small molecule inhibitors of XerC for P. aeruginosa infections
COMMERCIAL OPPORTUNITY
There is a large market opportunity due to the increased prevalence of multi-drug resistant bacterial infections, ventilator pneumonia associated with the SARS-Cov2 pandemic, immunocompromised populations, and growing awareness about antibiotic resistant bacterial infections. Globally in 2020, the P. aeruginosa treatment market was 933.8 million USD; this is (conservatively) projected to grow to 1.217 billion USD by 2027. We are seeking industry collaborators to help develop and commercialize our patent-pending technology in this growing market of critical, life-saving treatments.
STATE OF DEVELOPMENT
- Proof-of-concept has been established using in-vitro assays and mutant P. aeruginosa strains. Screening of small molecule inhibitors of XerC in P. aeruginosa cultures will soon commence.