<i>Limosilactobacillus fermentum</i> 3872 That Produces Class III Bacteriocin Forms Co-Aggregates with the Antibiotic-Resistant <i>Staphylococcus aureus</i> Strains and Induces Their Lethal Damage
Vyacheslav M. Abramov,
Igor V. Kosarev,
Andrey V. Machulin,
Tatiana V. Priputnevich,
Evgenia I. Deryusheva,
Ekaterina L. Nemashkalova,
Irina O. Chikileva,
Tatiana N. Abashina,
Alexander N. Panin,
Vyacheslav G. Melnikov,
Nataliya E. Suzina,
Ilia N. Nikonov,
Marina V. Selina,
Valentin S. Khlebnikov,
Vadim K. Sakulin,
Vladimir A. Samoilenko,
Alexey B. Gordeev,
Gennady T. Sukhikh,
Vladimir N. Uversky,
Andrey V. Karlyshev
Affiliations
Vyacheslav M. Abramov
Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, Russia
Igor V. Kosarev
Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, Russia
Andrey V. Machulin
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Tatiana V. Priputnevich
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health, 117997 Moscow, Russia
Evgenia I. Deryusheva
Institute for Biological Instrumentation, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Ekaterina L. Nemashkalova
Institute for Biological Instrumentation, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Irina O. Chikileva
Laboratory of Cell Immunity, Blokhin National Research Center of Oncology, Ministry of Health RF, 115478 Moscow, Russia
Tatiana N. Abashina
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Alexander N. Panin
Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, Russia
Vyacheslav G. Melnikov
Gabrichevsky Research Institute for Epidemiology and Microbiology, 125212 Moscow, Russia
Nataliya E. Suzina
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Ilia N. Nikonov
Federal State Educational Institution of Higher Professional Education, Moscow State Academy of Veterinary Medicine and Biotechnology named after K.I. Skryabin, 109472 Moscow, Russia
Marina V. Selina
Federal State Educational Institution of Higher Professional Education, Moscow State Academy of Veterinary Medicine and Biotechnology named after K.I. Skryabin, 109472 Moscow, Russia
Valentin S. Khlebnikov
Institute of Immunological Engineering, 142380 Lyubuchany, Russia
Vadim K. Sakulin
Institute of Immunological Engineering, 142380 Lyubuchany, Russia
Vladimir A. Samoilenko
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Alexey B. Gordeev
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health, 117997 Moscow, Russia
Gennady T. Sukhikh
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health, 117997 Moscow, Russia
Vladimir N. Uversky
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
Andrey V. Karlyshev
Department of Biomolecular Sciences, Faculty of Health, Science, Social Care and Education, Kingston University London, Kingston upon Thames KT1 2EE, UK
LF3872 was isolated from the milk of a healthy lactating and breastfeeding woman. Earlier, the genome of LF3872 was sequenced, and a gene encoding unique bacteriocin was discovered. We have shown here that the LF3872 strain produces a novel thermolabile class III bacteriolysin (BLF3872), exhibiting antimicrobial activity against antibiotic-resistant Staphylococcus aureus strains. Sequence analysis revealed the two-domain structural (lysozyme-like domain and peptidase M23 domain) organization of BLF3872. At least 25% residues of this protein are expected to be intrinsically disordered. Furthermore, BLF3872 is predicted to have a very high liquid-liquid phase separation. According to the electron microscopy data, the bacterial cells of LF3872 strain form co-aggregates with the S. aureus 8325-4 bacterial cells. LF3872 produced bacteriolysin BLF3872 that lyses the cells of the S. aureus 8325-4 mastitis-inducing strain. The sensitivity of the antibiotic-resistant S. aureus collection strains and freshly isolated antibiotic-resistant strains was tested using samples from women with lactation mastitis; the human nasopharynx and oral cavity; the oropharynx of pigs; and the cows with a diagnosis of clinical mastitis sensitive to the lytic action of the LF3872 strain producing BLF3872. The co-cultivation of LF3872 strain with various antibiotic-resistant S. aureus strains for 24 h reduced the level of living cells of these pathogens by six log. The LF3872 strain was found to be able to co-aggregate with all studied S. aureus strains. The cell-free culture supernatant of LF3872 (CSLF3872) induced S. aureus cell damage and ATP leakage. The effectiveness of the bacteriolytic action of LF3872 strain did not depend on the origin of the S. aureus strains. The results reported here are important for the creation of new effective drugs against antibiotic-resistant strains of S. aureus circulating in humans and animals.
