Collaborating with the Innate Immune System to Treat Multidrug-Resistant Superbugs
IKEEP. Marc Mendelson & Connie Walyaro
V. 11/23/20; 312914
Abstract
Collaborating with the Innate Immune System to Treat Multidrug-Resistant Superbugs
Victor Nizet, MD
University of California San Diego
Before the patient has even seen a doctor, their infection is already being treated by multiple antimicrobials - namely the cellular and molecular components of the innate immune system. Conventional screening paradigms in antibiotic discovery are based on MIC/MBC testing in conventional bacteriologic media, and similar tests on patient isolates are used to guide physician management. Antibiotics can synergize with endogenous antimicrobial peptides to effect bacterial killing. These studies will reveal how standard MIC testing can be misleading, overlooking potent antibiotic activities that are recognized only the context of the normal innate immune system. In this new discovery and treatment framework, drugs used in medicine for other indications (e.g. cholesterol-lowering or antiplatelet drugs), or antibiotics otherwise deemed ineffective, can be "repositioned" for treatment of multi-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) or carbapenemase-resistant strains of Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Victor Nizet, MD
University of California San Diego
Before the patient has even seen a doctor, their infection is already being treated by multiple antimicrobials - namely the cellular and molecular components of the innate immune system. Conventional screening paradigms in antibiotic discovery are based on MIC/MBC testing in conventional bacteriologic media, and similar tests on patient isolates are used to guide physician management. Antibiotics can synergize with endogenous antimicrobial peptides to effect bacterial killing. These studies will reveal how standard MIC testing can be misleading, overlooking potent antibiotic activities that are recognized only the context of the normal innate immune system. In this new discovery and treatment framework, drugs used in medicine for other indications (e.g. cholesterol-lowering or antiplatelet drugs), or antibiotics otherwise deemed ineffective, can be "repositioned" for treatment of multi-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) or carbapenemase-resistant strains of Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Collaborating with the Innate Immune System to Treat Multidrug-Resistant Superbugs
Victor Nizet, MD
University of California San Diego
Before the patient has even seen a doctor, their infection is already being treated by multiple antimicrobials - namely the cellular and molecular components of the innate immune system. Conventional screening paradigms in antibiotic discovery are based on MIC/MBC testing in conventional bacteriologic media, and similar tests on patient isolates are used to guide physician management. Antibiotics can synergize with endogenous antimicrobial peptides to effect bacterial killing. These studies will reveal how standard MIC testing can be misleading, overlooking potent antibiotic activities that are recognized only the context of the normal innate immune system. In this new discovery and treatment framework, drugs used in medicine for other indications (e.g. cholesterol-lowering or antiplatelet drugs), or antibiotics otherwise deemed ineffective, can be "repositioned" for treatment of multi-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) or carbapenemase-resistant strains of Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Victor Nizet, MD
University of California San Diego
Before the patient has even seen a doctor, their infection is already being treated by multiple antimicrobials - namely the cellular and molecular components of the innate immune system. Conventional screening paradigms in antibiotic discovery are based on MIC/MBC testing in conventional bacteriologic media, and similar tests on patient isolates are used to guide physician management. Antibiotics can synergize with endogenous antimicrobial peptides to effect bacterial killing. These studies will reveal how standard MIC testing can be misleading, overlooking potent antibiotic activities that are recognized only the context of the normal innate immune system. In this new discovery and treatment framework, drugs used in medicine for other indications (e.g. cholesterol-lowering or antiplatelet drugs), or antibiotics otherwise deemed ineffective, can be "repositioned" for treatment of multi-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) or carbapenemase-resistant strains of Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Funders
ISID Partner Organizations
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