Lead investigators: George C. Prendergast, PhD, and Melvin Reichman, PhD
Drug-resistant bacterial infections continue to pose a great challenge to healthcare. Antibiotics and other antimicrobial agents used since the 1940s to treat infectious diseases have greatly reduced their morbidity and mortality, but they have been used so widely and for so long that microbial strategies have evolved to bypass their effects, rendering them less effective.
Topical infections involving MRSA and other drug-resistant bacterial species are one area of risk. Building on concepts developed at LIMR to treat cancer by relieving immunosuppression in the local tumor microenvironment, our researchers have designed an antimicrobial formulation to treat infections by relieving immune barriers imposed by the local microbial ecology in which the infectious agent is embedded. Our formulation incorporates an FDA-approved substance that LIMR scientists discovered can effectively inhibit IDO, an immunosuppressive molecule that is elevated in certain infections associated with immune resistance (e.g., HPV).
Accordingly, the LIMR formulation seeks to treat drug-resistant infections as a problem of the microbiome, rather than solely of a specific pathogenic agent. By seeking to reverse the pathogenic effects of a supportive microbiome, this formulation may help enable clearance, either by boosting natural host immunity or by pharmacological synergy in combination with antimicrobial agents.
LIMR’s technology is a formulation that offers a new approach to eradicate drug-resistant topical infections by disrupting pathogenic microbiomes that suppress local immunity and wound healing responses that normally help clear infections. Moreover, the technology may be especially useful for immunosuppressed patient populations, including elders or patients undergoing chemotherapy.
As a potential over-the-counter formulation, the technology may also be used to leverage or expand the scope or effectiveness of other topical antibiotics or other drugs, the therapeutic action of which may be limited by an immunosuppressive “mal-microbiome” in which the infection is embedded.
This technology offers a leading edge in challenging the prevailing view that chronic, untreatable infections are caused wholly by drug-resistant genes acquired by a single pathogenic species. Microbiome research findings indicate a huge diversity in the microbial ecology in which any pathogenic infection must arise. Thus, it is conceivable that drug resistance reflects as much the local ecology of the microbiome as the embedded pathogenic species, for example, as in pathogenic biofilms. Clearing the “mal-microbiome” with LIMR’s approach might be sufficient to clear some infections—analogous to the ability of immune checkpoint inhibitors to restore latent tumor immunity—or possibly used in combination with antibiotics to re-empower their ability to clear drug-resistant infections.
Each year in the United States, at least two million people become infected with bacteria that are resistant to antibiotics, and at least 23,000 people die each year as a direct result of these infections, according to the U.S. Centers for Disease Control and Prevention. Drug-resistant skin infections, such as staph, MRSA and others, are a growing challenge. This drug formulation holds the potential to restore the immune system’s ability to eradicate dangerous topical infections, as well as promote wound healing.
Intellectual property position
Anti-microbial formulations to treat drug-resistant infections: Patent pending.
Muller AJ, DuHadaway JB, Jaller D, Curtis P, Metz R and Prendergast GC. (2010). Immunotherapeutic suppression of indoleamine 2,3-dioxygenase and tumor growth with ethyl pyruvate. Cancer Res 70: 1845-53.