Combined action of cationic peptide protegrins and antiseptics on biofilms formed by gram-positive and gram-negative bacteria
Vladimirova E.V., Sukhareva M.S., Tapilskaya N.I., Komlev A.S., Klimov N.A., Orlov D.S., Shamova O.V., Yakovlev A.A.
Background: The problems preventing successful treatment of recurrent infections are related to bacteria forming biofilms, which repeatedly increase microbe resistance to antibiotics. Therefore, the search for new anti-biofilm agents is an important issue. One of the most promising areas is the use of antimicrobial peptides.
Objective: To analyze the combined action of cationic antimicrobial peptide Protegrin-1 (PG-1) or Protegrin-2 (PG-2) with various antiseptics (Miramistin, Chlorhexidine, Povidone iodine, Dequalinium chloride, Prontosan wound irrigation solution (Prontosan solution)) used in the treatment of infections where the recurrent course is associated with biofilm formation.
Materials and methods: The antimicrobial activity against planktonic bacteria was determined using serial dilution method in liquid nutrient medium by chessboard titration to evaluate the co-activity. The antibiofilm activity was studied using crystal violet dye and viability marker, 2,3,5-triphenyltetrazolium chloride.
Results: Synergistic effects against planktonic forms of bacteria were observed when PG-1 or PG-2 were combined with Miramistin or Povidone iodine against Escherichia coli, and with Povidone iodine or Prontosan solution against Staphylococcus aureus. Synergism in inhibiting the viability of bacteria within the biofilm formed by Staphylococcus aureus was observed when PG-1 or PG-2 were used in combination with Dequalinium chloride, Povidone iodine and Prontosan solution. In most cases, the combination of protegrins and antiseptics had an additive or synergistic effect on both planktonic forms of bacteria and their biofilms.
Conclusion: The use of combined application of antimicrobial peptides PG-1 or PG-2 with antiseptics can be considered as a practical recommendation to improve the efficacy of medicines, cosmetics or medical devices containing protegrins. Their combined use with antiseptics will show a synergistic or additive effect on the development and destruction of biofilms formed by gram-positive, gram-negative bacteria.
Authors’ contributions: Shamova O.V. – developing the concept and design of the study; Vladimirova E.V., Sukhareva M.S. – conducting experiments, collecting and processing the material, statistical processing of the data; Komlev A.S. – peptide synthesis; Orlov D.S., Klimov N.A. – writing the text; Shamova O.V., Tapilskaya N.I., Orlov D.S., Yakovlev A.A. – editing the article.
Conflicts of interest: Authors declare lack of the possible conflicts of interest.
Funding: The study was performed under the contract No. 424-06-45/23 dated 15.12.2023 with Biotechpharm LLC, as well as under the state assignment of Institute of Experimental Medicine (FGWG-2025-0005).
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Vladimirova E.V., Sukhareva M.S., Tapilskaya N.I., Komlev A.S., Klimov N.A., Orlov D.S.,
Shamova O.V., Yakovlev A.A. Combined action of cationic peptide protegrins and antiseptics on biofilms
formed by gram-positive and gram-negative bacteria.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (5): 158-168 (in Russian)
https://dx.doi.org/10.18565/aig.2025.120
Keywords
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Received 06.05.2025
Accepted 19.05.2025
About the Authors
Elizaveta V. Vladimirova, Researcher at the Laboratory of Design and Synthesis of Biologically Active Peptides, Institute of Experimental Medicine,197022, Russia, St. Petersburg, Ac. Pavlov str., 12, https://orcid.org/0000-0002-6576-9844
Maria S. Sukhareva, Researcher at the Laboratory of Design and Synthesis of Biologically Active Peptides, Institute of Experimental Medicine,
197022, Russia, St. Petersburg, Ac. Pavlov str., 12, https://orcid.org/0000-0002-5351-7199
Aleksey S. Komlev, Researcher at the Laboratory of Design and Synthesis of Biologically Active Peptides, Institute of Experimental Medicine,
197022, Russia, St. Petersburg, Ac. Pavlov str., 12, https://orcid.org/0000-0001-9111-0755
Natalia I. Tapilskaya, Dr. Med. Sci., Professor, Leading Researcher, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology,
199034, Russia, St. Petersburg, Mendeleevskaya Line, 3, https://orcid.org/0000-0001-5309-0087
Nikolay A. Klimov, PhD, Leading Researcher at the Laboratory of Design and Synthesis of Biologically Active Peptides, Institute of Experimental Medicine,
197022, Russia, St. Petersburg, Ac. Pavlov str., 12, https://orcid.org/0000-0002-5243-8085
Dmitriy S. Orlov, PhD, Associate Professor, Head of the Laboratory of Design and Synthesis of Biologically Active Peptides, Institute of Experimental Medicine,
197022, Russia, St. Petersburg, Ac. Pavlov str., 12, https://orcid.org/0000-0003-2925-885X
Olga V. Shamova, Dr. Bio. Sci., Corresponding Member of RAS, Head of the Laboratory of Immunopathophysiology, Institute of Experimental Medicine,
197022, Russia, St. Petersburg, Ac. Pavlov str., 12, oshamova@yandex.ru, https://orcid.org/0000-0002-5168-2801
Alexandr A. Yakovlev, Director for Medical Research, Biotechpharm LLC, Moscow, https://orcid.org/0009-0000-3062-2159
Corresponding author: Olga V. Shamova, oshamova@yandex.ru