Engineered Endolysin LysECD7-SMAP Reveals Antimicrobial Synergy with Antibiotics and Restores Sensitivity in Gram-negative Pathogens

The demand for new treatment and prevention strategies of bacterial infections is increasing with the worldwide spread of acquired antimicrobial resistance among the microorganisms. This is especially important for healthcare-associated infections, exposed to a significant selective pressure of a closed system of in-patients organizations and pathogens’ propensity to the resistance factors transmission. In this work, we assessed the in vitro potential of a new therapy approach against Gram-negative species based on combination of conventional antibiotics and a modified bacteriophage-derived endolysin LysECD7-SMAP, belonging to the class of enzybiotics. We have shown that such combinations can not only manifest a synergistic effect, but also restore the sensitivity of the microorganism to the antibiotic. The mechanism of the endolysins antimicrobial action suggests absence or low risks of development of bacterial resistance, which means that such a therapeutic regimen could be safe for course application. This study can serve as a basis for the development of new treatment regimens for patients with severe, recurrent or relapse infections caused by drug-resistant pathogens.