TY - JOUR
T1 - The activity of 16 new hydantoin compounds on the intrinsic and overexpressed efflux pump system of staphylococcus aureus
AU - Dymek,, A.
AU - Armada, Ana Maria
AU - Handzlik,, J.
AU - Bettencourt, Miguel Viveiros
AU - Spengler , G,
AU - Molnar, , J.
AU - Kieć-Kononowicz,, K.
AU - Amaral, Leonard
PY - 2012/3
Y1 - 2012/3
N2 - Aim: To evaluate a new series of 16 hydantoin derivatives for activity against the intrinsic and overexpressed efflux pumps of the ATTC 25923 Staphylococcus aureus and the clinical Staphylococcus aureus HPV-107 strain, respectively. Materials and Methods: The hydantoin compounds were evaluated for activity against the efflux pumps of the ATTC 25923 S. aureus and the clinical S. aureus HPV-107 strains by the aid of the automated ethidium bromide method. Compounds that inhibited the efflux pumps of either strain were evaluated for ability to reduce or reverse resistance of these strains to oxacillin. Results: Although most of the hydantoins inhibited the efflux pumps of the ATTC strain, none reduced the resistance of this strain to oxacillin. In contrast, the inhibition of the Qac efflux pump present in HPV-107 was inhibited to some degree, by much higher concentrations of the hydantoin compounds than that needed for similar activity against the ATTC strain; only hydantoin PI8a significantly reduced the minimum inhibitory concentration of oxacillin against the HPV-107 strain. Conclusion: Hydantoin compound PI8a may have potential for therapy of a methicillin-resistant S. aureus infection whose multidrug-resistant phenotype is due to overexpression of an efflux pump.
AB - Aim: To evaluate a new series of 16 hydantoin derivatives for activity against the intrinsic and overexpressed efflux pumps of the ATTC 25923 Staphylococcus aureus and the clinical Staphylococcus aureus HPV-107 strain, respectively. Materials and Methods: The hydantoin compounds were evaluated for activity against the efflux pumps of the ATTC 25923 S. aureus and the clinical S. aureus HPV-107 strains by the aid of the automated ethidium bromide method. Compounds that inhibited the efflux pumps of either strain were evaluated for ability to reduce or reverse resistance of these strains to oxacillin. Results: Although most of the hydantoins inhibited the efflux pumps of the ATTC strain, none reduced the resistance of this strain to oxacillin. In contrast, the inhibition of the Qac efflux pump present in HPV-107 was inhibited to some degree, by much higher concentrations of the hydantoin compounds than that needed for similar activity against the ATTC strain; only hydantoin PI8a significantly reduced the minimum inhibitory concentration of oxacillin against the HPV-107 strain. Conclusion: Hydantoin compound PI8a may have potential for therapy of a methicillin-resistant S. aureus infection whose multidrug-resistant phenotype is due to overexpression of an efflux pump.
KW - intrinsic efflux pump
KW - hydantoin derivatives
KW - reversal of resistance to oxacillin
KW - inhibition of efflux pumps
KW - Staphylococcus aureus HPV-107
KW - Qac efflux pump
KW - Staphylococcus aureus ATCC 25923 wild-type
KW - oxacillin
KW - Staphylococcus aureus ATCC 25923 wild-type
KW - Staphylococcus aureus HPV-107
KW - Intrinsic efflux pump
KW - Qac efflux pump
KW - Hydantoin derivatives
KW - Oxacillin
KW - Inhibition of efflux pumps
KW - Reversal of resistance to oxacillin
M3 - Article
C2 - 22351662
SN - 0258-851X
VL - 26
SP - 223
EP - 229
JO - In Vivo
JF - In Vivo
IS - 2
ER -