Selective Eradication of Staphylococcus aureus by the Designer Genetically Programmed Yeast Biocontrol Agent

• Published in: Antibiotics (Basel) 2020-09, Vol.9 (9), p.527
• Main Authors: Pipiya, Sofiya O., Mokrushina, Yuliana A., Gabibov, Alexander G., Smirnov, Ivan V., Terekhov, Stanislav S.
• Format: Article
• Language: English
• Subjects: Antibacterial activity; Antibiotic resistance; Antibiotics; Biocompatibility; Biofilms; Biological control; Biological pest control; Biomedical materials; constitutive heterologous production in Pichia pastoris; Control; Decontamination; Ecological niches; Genetically modified organisms; genetically programmed probiotics; Health aspects; Lysis; Lysostaphin; Methods; Mutation; Penicillin; Probiotics; Pseudomonas aeruginosa; recombinant lysostaphin; Staphylococcus aureus; Staphylococcus aureus eradication; Staphylococcus infections; targeted lysis; Yeast; yeast biocontrol agent; Yeasts; Yeasts (Fungi)
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics9090527

Staphylococcus aureus is a common human pathogen that is particularly often associated with antibiotic resistance. The eradication of this ubiquitous infectious agent from its ecological niches and contaminated surfaces is especially complicated by excessive biofilm formation and persisting cells, which evade the antibacterial activity of conventional antibiotics. Here, we present an alternative view of the problem of specific S. aureus eradication. The constitutive heterologous production of highly specific bacteriolytic protease lysostaphin in yeast Pichia pastoris provides an efficient biocontrol agent, specifically killing S. aureus in coculture. A yeast-based anti-S. aureus probiotic was efficient in a high range of temperatures and target-to-effector ratios, indicating its robustness and versatility in eliminating S. aureus cells. The efficient eradication of S. aureus by live lysostaphin-producing P. pastoris was achieved at high scales, providing a simple, biocompatible and cost-effective strategy for S. aureus lysis in bioproduction and surface decontamination. Future biomedical applications based on designer yeast biocontrol agents require evaluation in in vivo models. However, we believe that this strategy is very promising since it provides highly safe, efficient and selective genetically programmed probiotics and targeted biocontrol agents.