Hyicin 4244, the first sactibiotic described in staphylococci, exhibits an anti-staphylococcal biofilm activity

• Published in: International journal of antimicrobial agents 2018-03, Vol.51 (3), p.349-356
• Main Authors: Duarte, Andreza Freitas de Souza, Ceotto-Vigoder, Hilana, Barrias, Emile Santos, Souto-Padrón, Thaïs Cristina Baeta Soares, Nes, Ingolf Figved, Bastos, Maria do Carmo de Freire
• Format: Article
• Language: English
• Subjects: Bacteriocin; Biofilm; Hyicin 4244; Sactibiotic; Staphylococcal infections; Staphylococcus
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2017.06.025

Anti-biofilm formation activity of hyicin 4244 (256 AU/mL) towards Staphylococcus saprophyticus 46s (B), a strong biofilm-former involved in human infection, compared with the control not treated with the bacteriocin (A) and observed by scanning electron microscopy. •Hyicin 4244 is the first sactibiotic to be described in staphylococci.•Hyicin 4244 has 35 amino acids and a gene cluster similar to that of subtilosin A.•Hyicin 4244 exhibits an anti-staphylococcal biofilm activity.•Hyicin 4244 significantly reduced biofilm formation by strong biofilm-formers.•Hyicin 4244 reduced cell proliferation and viability in established biofilms. Hyicin 4244 is a small antimicrobial peptide with a broad spectrum of activity that was found in the culture supernatant of Staphylococcus hyicus 4244, the genome of which was then sequenced. The bacteriocin gene cluster (hyiSABCDEFG) was mined from its single chromosome and exhibited a genetic organization similar to that of subtilosin A. All genes involved in hyicin 4244 biosynthesis proved to be transcribed and encode proteins that share at least 42% similarity to proteins encoded by the subtilosin A gene cluster. Due to its resemblance to subtilosin A and the presence of three thioether bonds in its structure, hyicin 4244 is assumed to be a 35–amino acid circular sactibiotic, the first to be described in staphylococci. Hyicin 4244 inhibited 14 staphylococcal isolates from either human infections or bovine mastitis, all biofilm formers. Hyicin 4244 significantly reduced the number of colony–forming units (CFU) and the biofilm formation by two strong biofilm-forming strains randomly chosen as representatives of the strains involved in human infections and bovine mastitis. It also reduced the proliferation and viability of sessile cells in established biofilms. Therefore, hyicin 4244 proved not only to prevent biofilm formation by planktonic cells, but also to penetrate the biofilm matrix in vitro, exerting bactericidal activity against staphylococcal sessile cells. This bacteriocin has the potential to become an alternative antimicrobial for either prevention or treatment of biofilm-related infections caused by different staphylococcal species.