A potential antimicrobial treatment against ESBL-producing Klebsiella pneumoniae using the tellurium compound AS101
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ORIGINAL PAPER
A potential antimicrobial treatment against ESBL-producing Klebsiella pneumoniae using the tellurium compound AS101 Miriam Daniel-HoVmann · Michael Albeck · Benjamin Sredni · Yeshayahu Nitzan
Received: 4 January 2009 / Revised: 21 May 2009 / Accepted: 26 May 2009 / Published online: 16 June 2009 © Springer-Verlag 2009
Abstract 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 Wrst time in this study. Eleven strains of K. pneumoniae were tested: Wve were extended spectrum beta lactamase (ESBL)-producing strains and six were non-ESBL-producing strains. The MIC and MBC of ten strains were 9 g/ml AS101 and 18 g/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 -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
B. Sredni and Y. Nitzan were equal collaborators in this research. Communicated by Sebastian Suerbaum. M. Daniel-HoVmann · B. Sredni · Y. Nitzan (&) The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, 52900 Ramat-Gan, Israel e-mail: [email protected] M. Daniel-HoVmann · B. Sredni The Mina and Everard Goodman Faculty of Life Sciences, The Safdié Institute for AIDS and Immunology Research, Bar-Ilan University, 52900 Ramat-Gan, Israel M. Albeck Department of Chemistry, Bar-Ilan University, 52900 Ramat Gan, Israel
microscopy showed that bacteria treated with AS101 or in combination with cysteamine exhibited evidence of cellwall 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. Keywords Klebsiella pneumoniae · ESBL · Tellurium compound · Antimicrobial agents
Introduction Klebsiella pneumoniae, an opportunistic pathogen, is one of the most common Gram-negative pathogens that can cause pneumonia, urinary tract infections, and sepsis in patients in intensive care units, and in immunocompromised individuals (Couto et al. 2007; Kappstein et al. 1991).Due to the extensive spread of antibiotic-resistant strains, especially extended-spectrum -lactamase (ESBL)producing strains, there has been renewed interest in developing alternative treatments for Klebsiella infections. The non-toxic immunomodulator, ammonium trichloro (dioxoethylene-o, o⬘) tellurate (AS101), is a low-molecular-weight (312 Da) synthetic organo-tellurium compound (Albeck et al. 1989). AS101 possesses immunomodulating properties (Rosenblatt-Bin
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