Novel leukotoxins from Staphylococcus aureus with significant potential for development of vaccines and therapeutics for MRSA infections
Victor J. Torres, PhD
Assistant Professor, Department of Microbiology
Background and Description of Technology:
Staphylococcus aureus poses a significant public health threat and is responsible for over 400,000 hospitalizations/year with 20 percent mortality. S. aureus is a leading cause of bacterial infections in hospitals and communities and highly difficult to control due to antibiotic resistance and lack of an effective vaccine. Thus, there is a significant unmet need in developing effective therapeutics and vaccines against S. aureus. A hallmark of infection includes targeting and suppression of the innate immune system by bacterial toxins. Therefore, reversing bacterial-mediated immune suppression is key to prevention and treatment of infection.
Dr. Torres has discovered a novel, bi-component leukotoxin, LukAB, produced by S. aureus. These secreted toxins specifically kill phagocytes (e.g., neutrophils, monocytes, macrophages and dendritic cells), by forming pores in their cell membranes. The production of these toxins allows S. aureus (including clinically relevant strains such as MRSA) to maintain an infectious state by down-regulating the immune response. Indeed, LukAB has potent cytotoxic activity specific for inflammatory phagocytic cells with little to no effect on other cell types. Dr. Torres has observed in that LukAB is the main S. aureus toxin responsible for (a) the bacteriaʼs ability to kill phagocytes and (b) protecting the bacteria from killing by phagocytes. Additionally, in a murine renal abscess model, lukAB was expressed in abscesses and a lukAB mutant was highly attenuated. Given its critical role in both ex vivo and in vivo models of S. aureus pathogenesis, LukAB is a very attractive candidate as an immunogen for a prophylactic or therapeutic vaccine, either alone or in combination with other immunogens. Moreover, inhibitors against LukAB can be used as a monotherapy against S. aureus or in combination with antibiotics.
A patent application has been filed on the composition and therapeutic use of LukAB. NYU is seeking commercial partners to develop LukAB-related vaccines and therapeutics for S. aureus infection.