Due to the extensive spread of antibiotic-resistant Klebsiella pneumoniae, the non-toxic immunomodulator, ammonium trichloro (dioxoethylene-o, o') tellurate (AS101), was introduced for the first time in this study. Eleven strains of K. pneumoniae were tested: five were extended spectrum beta lactamase (ESBL)-producing strains and six were non-ESBL-producing strains. The MIC and MBC of ten strains were 9 microg/ml AS101 and 18 microg/ml for one strain. AS101 treatment inhibited bacterial growth in a dose-dependent manner on protein-rich media. No inhibition by AS101 was observed on poorer media. In combination with beta-mercaptoethanol (2-ME) or cysteamine, AS101 inhibited bacterial growth in both types of media. Growth inhibition was also shown following AS101 treatment at both lag and log phases. Our data indicate that AS101 enters the bacterium through its porins, causing bacterial destruction. The mechanism of cell death was characterized using several techniques: (a) scanning electron microscopy showed that bacteria treated with AS101 or in combination with cysteamine exhibited evidence of cell-wall damage; (b) X-ray microanalysis demonstrated damage to Na/K pumps; and (c) transmission electron microscopy demonstrated cell lysis. These phenomena suggest that AS101 has antibacterial potential against K. pneumoniae infections.
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Acknowledgments The authors wish to thank Mrs. Rachel Dror for her excellent technical assistance and helpful comments, Dr. Izabella Pechatnikov for helping with liposome swelling assay, and Mr. OWr Avidan for help in preparing samples for TEM and for being a great colleague to consult with. This work was conducted as part of the ful-Wllments for a Ph.D. by Miriam Daniel-HoVmann. This work was partly supported by The Dr. Tovi Comet-Walerstein Cancer Research Chair, The Dave and Florence Muskovitz Chair in Cancer Research and The Frieda Stollman Cancer Memorial Fund. This research was also supported in part by the Rappaport Foundation for Microbiology, Bar-Ilan University, Israel (to YN).