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Pharmacological Inhibition of the ClpXP Protease Increases Bacterial Susceptibility to Host Cathelicidin Antimicrobial Peptides and Cell Envelope-Active Antibiotics
McGillivray, Shauna M. Tran, Dan N. Ramadoss, Nitya S. Alumasa, John N. Okumura, Cheryl Y. Sakoulas, George Vaughn, Micah M. Zhang, Dawn X. Keiler, Kenneth C. Nizet, Victor
McGillivray, Shauna M.
Tran, Dan N.
Ramadoss, Nitya S.
Alumasa, John N.
Okumura, Cheryl Y.
Sakoulas, George
Vaughn, Micah M.
Zhang, Dawn X.
Keiler, Kenneth C.
Nizet, Victor
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American Society for Microbiology
Date
2012-01-04
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Abstract
The ClpXP protease is a critical bacterial intracellular protease that regulates protein turnover in many bacterial species. Here we identified a pharmacological inhibitor of the ClpXP protease, F2, and evaluated its action in Bacillus anthracis and Staphylococcus aureus. We found that F2 exhibited synergistic antimicrobial activity with cathelicidin antimicrobial peptides and antibiotics that target the cell well and/or cell membrane, such as penicillin and daptomycin, in B. anthracis and drug-resistant strains of S. aureus. ClpXP inhibition represents a novel therapeutic strategy to simultaneously sensitize pathogenic bacteria to host defenses and pharmaceutical antibiotics.
Contents
Subject
wall stress stimulon
Staphylococcus Aureus
Bacillus Anthracis
Daptomycin
Virulence
Resistance
Proteolysis
Degradation
Infection
Proteins
Staphylococcus Aureus
Bacillus Anthracis
Daptomycin
Virulence
Resistance
Proteolysis
Degradation
Infection
Proteins
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Research Projects
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Department
Biology