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The alarming rate of antibiotic resistance is one of the major concerns of contemporary healthcare. The number of bacterial strains with multiple or extensive resistance keeps growing. Some of them do not respond to treatment with otherwise highly effective medications, including drugs of last resort; some become totally resistant “superbugs” causing persistent infections to any used antibiotic. Phage lysins have a few indisputable advantages over other antimicrobial agents. First, they are selective and attack only certain bacterial species while sparing the normal microbiota. Second, phage lysins ensure rapid lysis as they do not rely on slow metabolic reactions. Therefore, phage lysin-based therapies may not take as much time as standard antibacterial treatments. Third, the risk of developing resistance to phage lysins is low. Phage lysins target specific molecules crucial for the normal life cycle of the host, rendering emergence of a resistant isolate highly improbable as it would have to be accompanied by the massive rearrangement of the bacterial cell wall. Fourth, phage lysins can kill antibiotic-resistant bacterial strains providing a solution to one of the most pressing problems of contemporary healthcare. Fifth, due to their capacity to destabilize the peptidoglycan layer of the cell wall, phage lysins can both kill metabolically active or latently rested cells and access bacterial cells hidden by biofilms. In frame of the present work we describe a set of synthetic recombinant endolysins belongings to bacteriophages KPP10, Am24, Ap22, ECD7, Si3, St11. We describe its bactericidal activity against panel of laboratory and clinical strains of Gram-negative bacteria. In most of cases we observe 3-4 orders of magnitude decrease of bacteria load. Our findings confirm that lytic properties of phage lysins targeting gram-negative bacteria from both inside and outside the cell can be modified and enhanced by the use of permeabilizing agents. The results of our work are consistent with previously published data on endolysin KZ144 isolated from antipseudomonal bacteriophage phiKZ and endolysin OBPgpLYS that exhibited antimicrobial activity in the presence of permeabilizers. This gives hope for the discovery of therapeutic agents based on recombinant phage lysins that could become a real alternative to antibiotics.