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Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to β-lactam antibiotics.
Antimicrob Agents Chemother 2015; 59(3):1512-8AA

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.

Authors+Show Affiliations

Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.Center for Medical Mycology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.Center for Medical Mycology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, USA.Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA mxs10@case.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25534736

Citation

Kuo, David, et al. "Novel Quorum-quenching Agents Promote Methicillin-resistant Staphylococcus Aureus (MRSA) Wound Healing and Sensitize MRSA to Β-lactam Antibiotics." Antimicrobial Agents and Chemotherapy, vol. 59, no. 3, 2015, pp. 1512-8.
Kuo D, Yu G, Hoch W, et al. Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to β-lactam antibiotics. Antimicrob Agents Chemother. 2015;59(3):1512-8.
Kuo, D., Yu, G., Hoch, W., Gabay, D., Long, L., Ghannoum, M., ... Shoham, M. (2015). Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to β-lactam antibiotics. Antimicrobial Agents and Chemotherapy, 59(3), pp. 1512-8. doi:10.1128/AAC.04767-14.
Kuo D, et al. Novel Quorum-quenching Agents Promote Methicillin-resistant Staphylococcus Aureus (MRSA) Wound Healing and Sensitize MRSA to Β-lactam Antibiotics. Antimicrob Agents Chemother. 2015;59(3):1512-8. PubMed PMID: 25534736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to β-lactam antibiotics. AU - Kuo,David, AU - Yu,Guanping, AU - Hoch,Wyatt, AU - Gabay,Dean, AU - Long,Lisa, AU - Ghannoum,Mahmoud, AU - Nagy,Nancy, AU - Harding,Clifford V, AU - Viswanathan,Rajesh, AU - Shoham,Menachem, Y1 - 2014/12/22/ PY - 2014/12/24/entrez PY - 2014/12/24/pubmed PY - 2015/12/22/medline SP - 1512 EP - 8 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 59 IS - 3 N2 - 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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/25534736/Novel_quorum_quenching_agents_promote_methicillin_resistant_Staphylococcus_aureus__MRSA__wound_healing_and_sensitize_MRSA_to_β_lactam_antibiotics_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=25534736 DB - PRIME DP - Unbound Medicine ER -