Year: 2021
Type: article
Abstract: Endolysin-based therapeutics are promising antibacterial agents and can successfully supplement the existing antibacterial drugs array. It is specifically important in the case of Gram-negative pathogens, e.g., ESKAPE group bacteria, which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, and are highly inclined to gain multiple antibiotic resistance. Despite numerous works devoted to the screening of new lytic enzymes and investigations of their biochemical properties, there are significant breaches in some aspects of their operating characteristics, including safety issues of endolysin use. Here, we provide a comprehensive study of the antimicrobial efficacy aspects of four Gram-negative bacteria-targeting endolysins LysAm24, LysAp22, LysECD7, and LysSi3, their in vitro and in vivo activity, and their biological safety. These endolysins possess a wide spectrum of action, are active against planktonic bacteria and bacterial biofilms, and are effective in wound and burn skin infection animal models. In terms of safety, these enzymes do not contribute to the development of short-term resistance, are not cytotoxic, and do not significantly affect the normal intestinal microflora in vivo. Our results provide a confident base for the development of effective and safe candidate dosage forms for the treatment of local and systemic infections caused by Gram-negative bacterial species.
Source: Frontiers in Microbiology
Authors: Daria V. Vasina, Nataliia P. Antonova, Igor V. Grigoriev, Victoria S. Yakimakha, Anastasiya M. Lendel, Maria A. Nikiforova, Andrei A. Pochtovyi, Timofey A. Remizov, Evgeny V. Usachev, Natalia V. Shevlyagina, Vladimir G. Zhukhovitsky, Mikhail V. Fursov, Vasiliy D. Potapov, Aleksei M. Vorobev, Andrey V. Aleshkin, Aleksei I. Laishevtsev, Valentine V. Makarov, Sergey M. Yudin, Artem P. Tkachuk, Vladimir A. Gushchin
Institutions: Gamalei Institute of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Lomonosov Moscow State University, State Research Center for Applied Microbiology and Biotechnology, Gabrichevsky Institute of Epidemiology and Microbiology, All-Russian Scientific Research Institute of Experimental Veterinary Sciences. Ya.R. Kovalenko
Language: English
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: G1560510644, G471799057
OpenAlex ID: W3206404992