Next-Generation Antibiotics, Bacteriophage Endolysins, and Nanomaterials for Combating Pathogens

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NextGeneration Antibiotics, Bacteriophage Endolysins, and Nanomaterials for Combating Pathogens I. G. Shemyakin1, V. V. Firstova1,a*, N. K. Fursova1, I. V. Abaev1, S. Yu. Filippovich2, S. G. Ignatov1, and I. A. Dyatlov1

2

1 State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Moscow Region, Russia Bach Institute of Biochemistry, Research Center of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia a email: [email protected]

Received July 12, 2020 Revised September 14, 2020 Accepted September 14, 2020 Abstract—This review presents various strategies to fight causative agents of infectious diseases. Speciesspecific program mable RNAcontaining antibiotics open up new possibilities for creating nextgeneration of personalized drugs based on microbiome editing and can serve as a new tool for selective elimination of pathogenic bacterial species while keeping intact the rest of microbiota. Another promising approach in combating bacterial infections is genome editing using the CRISPR Cas systems. Expanding knowledge on the molecular mechanisms of innate immunity has been actively used for develop ing new antimicrobials. However, obvious risks of using antibiotic adjuvants aimed at activation of the host immune system include development of the autoimmune response with subsequent organ damage. To avoid these risks, it is essential to elu cidate action mechanisms of the specific ligands and signal molecules used as components of the hybrid antibiotics. Bacteriophage endolysins are also considered as effective antimicrobials against antibioticresistant bacteria, metabolically inactive persisters, and microbial biofilms. Despite significant advances in the design of implants with antibacterial proper ties, the problem of postoperative infections still remains. Different nanomodifications of the implant surface have been designed to reduce bacterial contamination. Here, we review bactericidal, fungicidal, and immunomodulating properties of compounds used for the implant surface nanomodifications, such as silver, boron nitride nanomaterials, nanofibers, and nanogalvanic materials. DOI: 10.1134/S0006297920110085 Keywords: RNAcontaining antibiotics, bacterial CRISPRCas systems, hybrid antibiotics, endolysins, nanosurfaces

INTRODUCTION

pathogens (RNAbased antibacterial preparations, hybrid antibiotics, bacteriophage endolysins, and nanomaterials).

The discovery of penicillin in 1929 has been immedi ately followed by identification of numerous bactericide agents. By the mid1960s, over 20 types of antibiotics had been described. The emergence of antibioticresistant pathogens, including panresistant isolates (i.e., microor ganisms resistant to all functional classes of antibiotics) stimulated further studies of the infectious agents and development of new approaches and drugs to fight Abbreviations: ACP, acetyl carrier protein; acpP, acyl carrier protein gene (gene encoding the protein involved in fatty acid biosynthesis); ASO, antisense oligonucleotide;