TY - JOUR
T1 - Thioridazine potentiates the effect of a beta-lactam antibiotic against Staphylococcus aureus independently of mecA expression
AU - Poulsen, Marianne Østergaard
AU - Jacobsen, Kirstine
AU - Thorsing, Mette
AU - Kristensen, Nadia R. D.
AU - Clasen, Julie
AU - Lillebæk, Eva Maria Sternkopf
AU - Skov, Marianne N.
AU - Kallipolitis, Birgitte H.
AU - Kolmos, Hans Jørn
AU - Klitgaard, Janne K.
PY - 2013
Y1 - 2013
N2 - The neuroleptic antipsychotic derivate thioridazine has been shown to increase the susceptibility of a methicillin-resistant Staphylococcus aureus (MRSA) isolate towards dicloxacillin. The aim of this study was to investigate the combinatorial effect of the two drugs on a broad selection of staphylococcal strains by analyzing a large collection of MRSA strains carrying different types of SCCmec, as well as MSSA strains. Transcription and translation of the resistance marker PBP2a encoded by mecA within the SCCmec cassette were analyzed by primer extension and western blotting.We observed increased susceptibility to dicloxacillin in the presence of thioridazine in all tested MRSA isolates. In contrast to previously published results, the synergistic effect was also applicable to methicillin-susceptible S. aureus (MSSA). We conclude that the combination of dicloxacillin and thioridazine potentiates the killing effect against S. aureus in a broad selection of clinical isolates. Additionally, the study indicates that the killing effect by the combinatorial treatment is independent of PBP2a-mediated resistance mechanisms.
AB - The neuroleptic antipsychotic derivate thioridazine has been shown to increase the susceptibility of a methicillin-resistant Staphylococcus aureus (MRSA) isolate towards dicloxacillin. The aim of this study was to investigate the combinatorial effect of the two drugs on a broad selection of staphylococcal strains by analyzing a large collection of MRSA strains carrying different types of SCCmec, as well as MSSA strains. Transcription and translation of the resistance marker PBP2a encoded by mecA within the SCCmec cassette were analyzed by primer extension and western blotting.We observed increased susceptibility to dicloxacillin in the presence of thioridazine in all tested MRSA isolates. In contrast to previously published results, the synergistic effect was also applicable to methicillin-susceptible S. aureus (MSSA). We conclude that the combination of dicloxacillin and thioridazine potentiates the killing effect against S. aureus in a broad selection of clinical isolates. Additionally, the study indicates that the killing effect by the combinatorial treatment is independent of PBP2a-mediated resistance mechanisms.
KW - MRSA
KW - Thioridazine
KW - Beta-lactam antibiotic
KW - Susceptibility
U2 - 10.1016/j.resmic.2012.10.007
DO - 10.1016/j.resmic.2012.10.007
M3 - Journal article
C2 - 23089256
SN - 0923-2508
VL - 164
SP - 181
EP - 188
JO - Research in Microbiology
JF - Research in Microbiology
IS - 2
ER -