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Immunomimetic Designer Cells Protect Mice from MRSA Infection.

Cell | 2018

Many community- and hospital-acquired bacterial infections are caused by antibiotic-resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) predisposes humans to invasive infections that are difficult to eradicate. We designed a closed-loop gene network programming mammalian cells to autonomously detect and eliminate bacterial infections. The genetic circuit contains human Toll-like receptors as the bacterial sensor and a synthetic promoter driving reversible and adjustable expression of lysostaphin, a bacteriolytic enzyme highly lethal to S. aureus. Immunomimetic designer cells harboring this genetic circuit exhibited fast and robust sense-and-destroy kinetics against live staphylococci. When tested in a foreign-body infection model in mice, microencapsulated cell implants prevented planktonic MRSA infection and reduced MRSA biofilm formation by 91%. Notably, this system achieved a 100% cure rate of acute MRSA infections, whereas conventional vancomycin treatment failed. These results suggest that immunomimetic designer cells could offer a therapeutic approach for early detection, prevention, and cure of pathogenic infections in the post-antibiotic era.

Pubmed ID: 29937224 RIS Download

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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ClinicalTrials.gov (tool)

RRID:SCR_002309

Registry and results database of federally and privately supported clinical trials conducted in United States and around world. Provides information about purpose of trial, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from health care professionals.Offers information for locating federally and privately supported clinical trials for wide range of diseases and conditions. Research study in human volunteers to answer specific health questions. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings. ClinicalTrials.gov contains trials sponsored by National Institutes of Health, other federal agencies, and private industry. Studies listed in database are conducted in all 50 States and in 178 countries.

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RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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RRID:AB_2337534

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RRID:CVCL_Z015

Cell line hMSC-TERT is a Telomerase immortalized cell line with a species of origin Homo sapiens (Human)

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RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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Cell line BHK-21 clone 13 is a Spontaneously immortalized cell line with a species of origin Mesocricetus auratus

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HEK293T/17 (cell line)

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Cell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)

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Benchling (web application)

RRID:SCR_013955

An online resource which helps researchers manage and organize labs and experimental results by supplying molecular biology software tools for experimental design and data analysis. Benchling provides tools for functions such as primer design and colony counting as well as CRISPR guide design and automated Gibson and Golden Gate cloning. Users can take notes in line with data, link data across entries, keep files and data in one place, and manage and keep track of team progress. An enterprise version of Benchling is available for scientists working within an organization with additional administrative, compliance, and security protocols.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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AffiniPure Goat Anti-Human IgG, Fc_ Fragment Specific (antibody)

RRID:AB_2337534

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hMSC-TERT (cell line)

RRID:CVCL_Z015

Cell line hMSC-TERT is a Telomerase immortalized cell line with a species of origin Homo sapiens (Human)

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HT-1080 (cell line)

RRID:CVCL_0317

Cell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)

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HT-1080 (cell line)

RRID:CVCL_0317

Cell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)

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