Novel Quorum-Quenching Agents Promote Methicillin-Resistant Staphylococcus aureus (MRSA) Wound Healing and Sensitize MRSA to β-Lactam Antibiotics | Zendy

David Kuo | Zendy; Guan-Ping Yu | Zendy; Wyatt B. Hoch | Zendy; Dean Gabay | Zendy; Lisa Long | Zendy; Mahmoud A. Ghannoum | Zendy; Nancy Nagy | Zendy; Clifford V. Harding | Zendy; Rajesh Viswanathan | Zendy; Menachem Shoham | Zendy

Open Access

Novel Quorum-Quenching Agents Promote Methicillin-Resistant Staphylococcus aureus (MRSA) Wound Healing and Sensitize MRSA to β-Lactam Antibiotics

Author(s) -

David Kuo,

Guan-Ping Yu,

Wyatt B. Hoch,

Dean Gabay,

Lisa Long,

Mahmoud A. Ghannoum,

Nancy Nagy,

Clifford V. Harding,

Rajesh Viswanathan,

Menachem Shoham

Publication year - 2014

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.04767-14

Subject(s) - nafcillin , quorum quenching , staphylococcus aureus , antibiotics , microbiology and biotechnology , methicillin resistant staphylococcus aureus , vancomycin , quorum sensing , staphylococcal infections , medicine , mupirocin , biology , biofilm , bacteria , penicillin , genetics

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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