Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens

Viruses

ValentineV. Makarov¹  AnastasiyaM. Lendel²  AlexanderL. Gintsburg³  NataliiaP. Antonova³  ArtemP. Tkachuk³  EvgenyV. Usachev³  DariaV. Vasina³  VladimirA. Gushchin³ 

[1] Center for Strategic Planning of the Ministry of Health of the Russian Federation, 119435 Moscow, Russia;Lomonosov Moscow State University, 119991 Moscow, Russia;N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia;

关键词: bacteriophages;    Myoviridae;    bacteriophage-derived lytic enzyme;    enzybiotics;    endolysin;    in vitro activity;    ESKAPE;   

DOI  :  10.3390/v11030284

来源: DOAJ

【 摘 要 】

The extremely rapid spread of multiple-antibiotic resistance among Gram-negative pathogens threatens to move humankind into the so-called “post-antibiotic era„ in which the most efficient and safe antibiotics will not work. Bacteriophage lysins represent promising alternatives to antibiotics, as they are capable of digesting bacterial cell wall peptidoglycans to promote their osmotic lysis. However, relatively little is known regarding the spectrum of lysin bactericidal activity against Gram-negative bacteria. In this study, we present the results of in vitro activity assays of three putative and newly cloned Myoviridae bacteriophage endolysins (LysAm24, LysECD7, and LysSi3). The chosen proteins represent lysins with diverse domain organization (single-domain vs. two-domain) and different predicted mechanisms of action (lysozyme vs. peptidase). The enzymes were purified, and their properties were characterized. The enzymes were tested against a panel of Gram-negative clinical bacterial isolates comprising all Gram-negative representatives of the ESKAPE group. Despite exhibiting different structural organizations, all of the assayed lysins were shown to be capable of lysing Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Salmonella typhi strains. Less than 50 μg/mL was enough to eradicate growing cells over more than five orders of magnitude. Thus, LysAm24, LysECD7, and LysSi3 represent promising therapeutic agents for drug development.

【 授权许可】

Unknown