title: Natural antimicrobial peptide complexes in the fighting of antibiotic resistant biofilms: Calliphora vicina medicinal maggots.
abstract: Biofilms, sedimented microbial communities embedded in a biopolymer matrix cause vast majority of human bacterial infections and many severe complications such as chronic inflammatory diseases and cancer. Biofilms' resistance to the host immunity and antibiotics makes this kind of infection particularly intractable. Antimicrobial peptides (AMPs) are a ubiquitous facet of innate immunity in animals. However, AMPs activity was studied mainly on planktonic bacteria and little is known about their effects on biofilms. We studied structure and anti-biofilm activity of AMP complex produced by the maggots of blowfly Calliphora vicina living in environments extremely contaminated by biofilm-forming germs. The complex exhibits strong cell killing and matrix destroying activity against human pathogenic antibiotic resistant Escherichia coli, Staphylococcus aureus and Acinetobacter baumannii biofilms as well as non-toxicity to human immune cells. The complex was found to contain AMPs from defensin, cecropin, diptericin and proline-rich peptide families simultaneously expressed in response to bacterial infection and encoded by hundreds mRNA isoforms. All the families combine cell killing and matrix destruction mechanisms, but the ratio of these effects and antibacterial activity spectrum are specific to each family. These molecules dramatically extend the list of known anti-biofilm AMPs. However, pharmacological development of the complex as a whole can provide significant advantages compared with a conventional one-component approach. In particular, a similar level of activity against biofilm and planktonic bacteria (MBEC/MIC ratio) provides the complex advantage over conventional antibiotics. Available methods of the complex in situ and in vitro biosynthesis make this idea practicable.
authors.affiliation: Laboratory of Insect Biopharmacology and Immunology, Faculty of Biology, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gordya
authors.affiliation: Laboratory of Insect Biopharmacology and Immunology, Faculty of Biology, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Yakovlev
authors.affiliation: Laboratory of Insect Biopharmacology and Immunology, Faculty of Biology, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kruglikova
authors.affiliation: Laboratory of Insect Biopharmacology and Immunology, Faculty of Biology, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Tulin
authors.affiliation: Laboratory of Insect Biopharmacology and Immunology, Faculty of Biology, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Evdokia
authors.initials: E
authors.lastname: Potolitsina
authors.affiliation: Research Center of Kirov Military Medical Academy, St. Petersburg, Russia.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Suborova
authors.affiliation: IRCCS AOU San Martino IST - National Institute for Cancer Research, Genova, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Bordo
authors.affiliation: IRCCS AOU San Martino IST - National Institute for Cancer Research, Genova, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Rosano
authors.affiliation: Laboratory of Insect Biopharmacology and Immunology, Faculty of Biology, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Chernysh
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D001688:Biological Products; D004175:Diptera / Q000502:physiology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D007814:Larva / Q000502:physiology*; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001688:Biological Products