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

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.

SUBMITTER: Pipiya SO

PROVIDER: S-EPMC7559405 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Pipiya Sofiya O SO Mokrushina Yuliana A YA Gabibov Alexander G AG Smirnov Ivan V IV Terekhov Stanislav S SS

Antibiotics (Basel, Switzerland) 20200819 9

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 pr ...[more]

PMID: 32824911

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Project description:Staphylococcus aureus is one of the major pathogens responsible for intramammary infections in small ruminants, causing severe economic losses in dairy farms. In addition, S. aureus can contaminate milk and dairy products and produce staphylococcal enterotoxins, being responsible for staphylococcal food poisoning. Currently, data on the population structure and the virulence gene patterns of S. aureus strains isolated from goat milk is limited. Therefore, this study aimed at defining Ribosomal Spacer PCR (RS-PCR) genotypes, clonal complexes (CC), spa types, and virulence gene profiles of S. aureus isolated from goat milk samples from Lombardy region of Italy. A total of 295 S. aureus isolates from 65 goat bulk tank milk samples were genotyped by RS-PCR. spa typing and virulence gene patterns of a subgroup of 88 isolates were determined, and MLST was performed on a further subgroup of 39 isolates, representing all the spa types identified during the analysis. This study revealed 7 major genotypic clusters (CLR, CLAA, CLZ, CLAW, CLBW, CLS, and CLI), of which S. aureus CLR (19.8%) was the most common. A total of 26 different spa types were detected, the most prevalent types were t1773 (24%), t5428 (22.7%), and t2678 (12.5%). Overall, 44.3% of all isolates harbored at least one enterotoxin gene. The most prevalent was the combination of sec-sel genes (35.2%). Based on their MLST, isolates were assigned to 14 different CC, with majority grouped as CC133 (24%), CC130 (19.6%), and CC522 (19.6%). The caprine S. aureus population was depicted with a minimum spanning tree and an evolutionary analysis based on spa typing and MLST, respectively. Then, the variability of such strains was compared to that of bovine strains isolated in the same space-time span. Our results confirmed that S. aureus isolates from goats have wide genetic variability and differ from the bovine strains, supporting the idea that S. aureus from small ruminants may constitute a distinct population.

Dataset Information

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

Publications

Selective Eradication of <i>Staphylococcus aureus</i> by the Designer Genetically Programmed Yeast Biocontrol Agent.

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