title: An improved susceptibility test based on Amberlite reveals the potential antilisterial activity of fosfomycin in vitro.
abstract: Listeria monocytogenes is resistant to fosfomycin in vitro but is susceptible in vivo due to increased expression of positive regulator factor A (PrfA) and its dependent factor, hexose phosphate transporter (Hpt), upon infection of host cells. Amberlite, a polymeric adsorbent resin, could induce PrfA-dependent gene expression and thus, in theory, improve the sensitivity of L. monocytogenes to fosfomycin in vitro. In the current study, an improved susceptibility test based on Amberlite was developed using reference strains. Thirty-five clinical isolates were further examined to verify those preliminary results. Briefly, Amberlite increased in vitro fosfomycin sensitivity of all strains. Optimal Amberlite concentrations, as evaluated through the expression of phospholipase B (PlcB) and Hpt, were 10% and 15% (w/v) in agar media and 3% (w/v) in broth media. Mueller-Hinton (MH) medium, tryptone soya (TS) medium, and brain heart infusion (BHI) medium were used to verify the results in the control strains using agar dilution and broth micro- and macro-dilution methods. Better listerial growth was shown in TS and BHI than in MH. Both broth dilution methods yielded lower minimal inhibitory concentration (MIC) of fosfomycin than the agar dilution method. The MIC of fosfomycin for 35 clinical isolates was 2-32 μg/mL, suggesting improved susceptibility. In conclusion, in vitro sensitivity of L. monocytogenes to fosfomycin was substantially improved in the presence of 3% Amberlite-supplemented TSB or BHIB and the broth microdilution method. This improved method revealed the potential antilisterial activity of fosfomycin in vitro and could facilitate the therapy of listeriosis using fosfomycin.
authors.affiliation: Department of Immunology and Pathogenic Biology, College of Medicine, Xi'an Jiaotong University, 76 West Yanta Road, Xi'an 710061, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Jin'e
authors.initials: J
authors.lastname: Lei
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Ma
authors.forename: Pengbo
authors.initials: P
authors.lastname: Yu
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Wu
authors.forename: Jiru
authors.initials: J
authors.lastname: Xu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003470:Culture Media; D024881:Drug Resistance, Bacterial; D005578:Fosfomycin / Q000494:pharmacology*; D006801:Humans; D008089:Listeria monocytogenes / Q000187:drug effects*; D008088:Listeriosis / Q000188:drug therapy; D008826:Microbial Sensitivity Tests / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction; D012117:Resins, Synthetic / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D012117:Resins, Synthetic; D005578:Fosfomycin; C046797:amberlite