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2015 ; 59
(3
): 1512-8
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Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus
(MRSA) wound healing and sensitize MRSA to ?-lactam antibiotics
#MMPMID25534736
Kuo D
; Yu G
; Hoch W
; Gabay D
; Long L
; Ghannoum M
; Nagy N
; Harding CV
; Viswanathan R
; Shoham M
Antimicrob Agents Chemother
2015[Mar]; 59
(3
): 1512-8
PMID25534736
show ga
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 ?g/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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