Antibiotic-resistant infections are an increasing cause for concern. According to the CDC’s 2019 Antibiotic Resistant Threats in the United States report, more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, resulting in over 35,000 deaths.1 Researchers have identified 18 bacteria and fungi species of particular concern to public health and safety due to their development of resistance in clinical settings. 1
Despite U.S. infection and prevention control efforts, the national cost of treating infections is more than $4.6 billion a year.2 The overuse and misuse of antibiotics in treating infections will only accelerate antibiotic resistance. Oragenics is pursuing the commercial-scale production of lantibiotics used to treat antibiotic-resistant infectious diseases. Because of our novel and unique mechanism of action, our work with lantibiotics will address several limitations related to current drugs on the market.
Novel Approach & Opportunity
The need for lantibiotics is skyrocketing due to the increased risk of the development of antimicrobial resistance—particularly in healthcare settings.
Oragenics lantibiotics are characterized by a novel mechanism of action designed to fight bacterial infections. These lantibiotics are engineered to limit the development of antibiotic resistance. We have previously shown that this class of compounds can be extremely effective in several animal models of infection and during preclinical testing.3
How Lantibiotics Work
Lantibiotics originate from several Gram-positive bacterial species. These potent antimicrobial agents are effective against bacteria that cause healthcare-acquired infections, or HAIs, by binding with and sequestering their molecular target, Lipid II (shown to be an attractive target for antibiotics).3
Oragenics has discovered a novel mechanism of action for lantibiotics—a breakthrough that may help reduce antibiotic resistance in bacterial strains that are inherently resistant to front-line therapies.
In the past, pharmaceutical-grade lantibiotics have been difficult to manufacture using traditional fermentation methods, because producing organisms are also sensitive to their own lantibiotics. Oragenics has made significant strides in resolving some of the most important limitations of lantibiotic manufacturing by developing innovative methods for large-scale production and purification of pharmaceutical-grade compounds.
Proof of Concept Research
Mutacin 1140 (MU1140), a lantibiotic, was discovered by the founder of Oragenics.3 Groundbreaking work on MU1140 has demonstrated the clinical and therapeutic potential of this novel antimicrobial.3 More recently, over 700 analogs of the MU1140 molecule were engineered, manufactured, and tested for several critical parameters in order to assess their “drugability” (the ability of a compound to be used commercially as a pharmaceutical drug, taking into account technical and financial considerations). These parameters included their safety, toxicity, stability, manufacturability, and drug activity compared to so-called “drugs of last resort.”3 Several animal studies were performed to confirm the efficacy of our compounds against significant human pathogens.3
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Florida International University
Since 2017, Oragenics has been collaborating with scientists at Florida International University (FIU) and FIU’s Biomolecular Sciences Institute. Using molecular modeling, we have been able to further investigate lantibiotics’ mechanism of action and as a result, develop novel compounds based on the lessons learned from this research. As part of this collaboration, a new and potentially significant mechanism of action was discovered, which may reveal new lead compounds against an expanded list of multidrug resistant human pathogens.3
Oragenics was recently awarded a Small Business Innovation Research (SBIR) grant from the National Institute of General Medical Sciences (NIGMS) to support some of our collaborations with FIU (“Computer-Aided Design for Improved Lantibiotics” R41GM136034).4
Other Antimicrobial Candidates
As part of our research and development program, Oragenics will continue to focus on creating variations of MU1140 that fight against ESKAPE pathogens (a group of six pathogens that are resistant to antibiotics), which have been recognized by the CDC and other authorities as priority pathogens. The emerging spread of antimicrobial resistance remains a major national concern. Lantibiotics may offer an untapped source of viable solutions to this problem.