Gram negative Lysins
Gram negative Lysins
OVERVIEW
The focus of our research and discovery efforts is on identifying and engineering lysins which selectively kill specific species of Gram-negative bacteria. Emerging strains of multi-drug resistant (MDR) Gram-negative pathogens that are resistant to all or nearly all available antibiotics are considered to be urgent or serious health threats by global health authorities. We believe that lysins which target Gram-negative pathogens have the potential to be important therapeutics to combat antimicrobial resistance due to their novel mechanism of action and therapeutic profile, which is complimentary to conventional antibiotics. We have initially focused on Pseudomonas aeruginosa (P. aeruginosa) and identified candidates with potent in vitro activity against P. aeruginosa and continue to screen and characterize candidates targeted against additional Gram-negative pathogens such as Escherichia coli, Enterobacter cloacae, and Klebsiella pneumoniae. In March 2017, ContraFect was awarded a grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) to support the development of lysins to treat infections caused by P. aeruginosa. In January 2019, CARB-X increased the amount of the grant by $2.3 million.
GRAM-NEGATIVE PATHOGENS
Antibiotic resistance is a growing threat to public health and to the provision of health care worldwide. Infections caused by antibiotic-resistant pathogens substantially increase the burden of both healthcare-associated infections and community-acquired infections. Infections caused by drug-resistant Gram-negative pathogens result in greater all-cause mortality, in-hospital mortality and length of hospitalization. For example, drug-resistant P. aeruginosa infections increase in-hospital mortality by more than 5x and length of hospitalization by more than 2x compared to susceptible isolates.
Several factors have contributed to the emergence and spread of antibiotic resistance worldwide, including inappropriate antibiotic usage, extensive use in agricultural and veterinary sectors, aging populations, increasing numbers of immunocompromised individuals, growing global travel and migration from countries that have higher levels of antibiotic-resistant pathogens, and an inadequate number of new antibiotics in the development pipeline. We aim to address this deficiency with our novel, differentiated lysins targeting Gram-negative pathogens. Similar to exebacase, our Gram-negative targeted lysins should act faster than and synergistically with standard-of-care antibiotics, have a potent, yet specific, spectrum of activity that spares the healthy gastrointestinal microbiome, and rapidly clear biofilms.
