Abstract
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.
Highlights
Antibiotic resistance (AR) is a persistent threat to global healthcare, resulting in up to 11 million deaths annually [1,2]
The efficient eradication of S. aureus by live Recombinant lysostaphin-producing (rLys) P. pastoris was achieved at high scales, resulting in a simple and cost-effective strategy for S. aureus lysis in bioproduction and surface decontamination
Pichia pastoris GS115 was used as a heterologous host for secreted lysostaphin production. rLys P. pastoris and the control mCherry-producing strain were obtained from Pichia pastoris GS115, transformed with pGAP-rLys or pGAP-mCherry, respectively
Summary
Antibiotic resistance (AR) is a persistent threat to global healthcare, resulting in up to 11 million deaths annually [1,2]. The exceptionally flexible S. aureus adaptation to antibiotics arises from the horizontal transfer of mobile genetic elements. It is enhanced by increased mutation rates of S. aureus strains. The estimated mutation rate for the S. aureus isolate collection is 3.3 × 10−6 per site per year [6]. This rate is about 1000 times faster than the canonical substitution rate estimate for E. coli [7]. A high mutation rate of S. aureus isolates relates to their low doubling time in the Antibiotics 2020, 9, 527; doi:10.3390/antibiotics9090527 www.mdpi.com/journal/antibiotics
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.