A potential antimicrobial treatment against ESBL-producing Klebsiella pneumoniae using the tellurium compound AS101

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 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.

Bactericidal activity of the organo-tellurium compound AS101 against Enterobacter cloacae

“…48 The XRMA results with E. cloacae are similar to results demonstrated for K. pneumoniae with the same drug. 8 The TEM and SEM images support the findings obtained by XRMA and ICPMS. The empty cells seen by TEM are probably a result of leakage of the cell contents.…”

“…The same phenomenon was found with K. pneumoniae. 8 It seems that the reason is not only because BHI contains a higher protein concentration than NB medium (15-fold), 41 but also because it contains a high level of thiols. This is an outcome of the fact that Te (IV) compounds readily interact with thiols to form Te(thiol)4 compounds.…”

“…8 In the current study, presentation of the spectrum of the antibacterial effect of AS101 was expanded to another species of the Enterobacteriaceae family. This time the drug was examined against E. cloacae.…”

“…The method has been described for bacterial cultures previously by Daniel-Hoffmann et al, 8 Malik et al 32 and Nitzan et al 33 All X-ray spectra were taken with the same count rate. 34 …”

“…This laboratory has recently shown a direct antimicrobial effect of AS101 on extended-spectrum b-lactamase (ESBL) and non-ESBL-producing strains of Klebsiella pneumoniae. 8 Enterobacter cloacae comprises part of the normal flora of the gastrointestinal tract of 40% -80% of the population and is widely distributed in the environment. 9,10 Like most members of the Enterobacteriaceae family, these microorganisms are important nosocomial pathogens capable of causing opportunistic infections among hospitalized or debilitated 9,11 -14 and immunosuppressed patients.…”