Journal article
NLRP3 Inflammasome Is a Target for Development of Broad-Spectrum Anti-Infective Drugs
Antimicrobial agents and chemotherapy, v 56(4), pp 1921-1930
Apr 2012
PMID: 22290938
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We describe the molecular mode of action and pharmacodynamics of a new molecular entity (NME) that induces the NLRP3 inflammasome-mediated innate immune response. This innate response reduces the pathogen load in an experimentally induced methicillin-resistant
Staphylococcos aureus
infection, enhances survival in an experimentally induced Gram-negative bacteremia, and overrides the escape mechanism of an obligate intracellular pathogen,
viz
.
Chlamydia pneumoniae
. Furthermore, the NME is more effective than standard-of-care antibiotic therapy in a clinically established multifactorial bacterial infection. Analysis of transcriptional regulation of inflammasome signaling genes and innate/adaptive immune genes revealed consistent and significant host changes responsible for the improved outcomes in these infections. These studies pave the way for the development of first-in-class drugs that enhance inflammasome-mediated pathogen clearance and identify the NLRP3 inflammasome as a drug target to address the global problem of emerging new infectious diseases and the reemergence of old diseases in an antibiotic-resistant form.
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Details
- Title
- NLRP3 Inflammasome Is a Target for Development of Broad-Spectrum Anti-Infective Drugs
- Creators
- James D Thacker - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USABrian J Balin - Department of Pathology, Microbiology, and Immunology, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, USADenah M Appelt - Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, USASihem Sassi-Gaha - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAMitali Purohit - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USARichard F Rest - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USACarol M Artlett - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
- Publication Details
- Antimicrobial agents and chemotherapy, v 56(4), pp 1921-1930
- Publisher
- American Society for Microbiology; 1752 N St., N.W., Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; [Retired Faculty]
- Web of Science ID
- WOS:000301898500032
- Scopus ID
- 2-s2.0-84858676971
- Other Identifier
- 991014877977604721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy