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Antimicrobial agents and chemotherapy
Mar, 2015;59 (3): 1512-8.

Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to β-lactam antibiotics.

David Kuo, Guanping Yu, Wyatt Hoch, Dean Gabay, Lisa Long, Mahmoud Ghannoum, Nancy Nagy, Clifford V Harding, Rajesh Viswanathan, Menachem Shoham
Author Information
  1. David Kuo: Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
  2. Guanping Yu: Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
  3. Wyatt Hoch: Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
  4. Dean Gabay: Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
  5. Lisa Long: Center for Medical Mycology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
  6. Mahmoud Ghannoum: Center for Medical Mycology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
  7. Nancy Nagy: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  8. Clifford V Harding: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  9. Rajesh Viswanathan: Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, USA.
  10. Menachem Shoham: Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA mxs10@case.edu.
PMID: 25534736 DOI: 10.1128/AAC.04767-14

Abstract

The dwindling repertoire of antibiotics to treat methicillin-resistant Staphylococcus aureus (MRSA) calls for novel treatment options. Quorum-quenching agents offer an alternative or an adjuvant to antibiotic therapy. Three biaryl hydroxyketone compounds discovered previously (F1, F12, and F19; G. Yu, D. Kuo, M. Shoham, and R. Viswanathan, ACS Comb Sci 16:85-91, 2014) were tested for efficacy in MRSA-infected animal models. Topical therapy of compounds F1 and F12 in a MRSA murine wound infection model promotes wound healing compared to the untreated control. Compounds F1, F12, and F19 afford significant survival benefits in a MRSA insect larva model. Combination therapy of these quorum-quenching agents with cephalothin or nafcillin, antibiotics to which MRSA is resistant in monotherapy, revealed additional survival benefits. The quorum-quenching agents sensitize MRSA to the antibiotic by a synergistic mode of action that also is observed in vitro. An adjuvant of 1 μg/ml F1, F12, or F19 reduces the MIC of nafcillin and cephalothin about 50-fold to values comparable to those for vancomycin, the antibiotic often prescribed for MRSA infections. These findings suggest that it is possible to resurrect obsolete antibiotic therapies in combination with these novel quorum-quenching agents.

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MeSH Term

Animals
Anti-Bacterial Agents
Cell Line
Cephalothin
Macrophages
Methicillin-Resistant Staphylococcus aureus
Mice
Microbial Sensitivity Tests
Nafcillin
Quorum Sensing
Wound Healing
beta-Lactams

Chemicals

Anti-Bacterial Agents
beta-Lactams
Nafcillin
Cephalothin
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 4

Word Cloud

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