Phosphorylation of Kanamycin, Lividomycin A, and Butirosin B by Providencia stuartii

Abstract

The isolation of Providencia stuartii resistant to multiple aminoglycoside antibiotics prompted an investigation into the mechanism of their resistance. Crude enzyme extracts of a strain of P. stuartii inactivated kanamycin, lividomycin A, and butirosin B in the presence of adenosine 5′-triphosphate (ATP), as measured by a microbiological assay. The occurrence of inhibitory concentrations of 500 μg or greater per ml against kanamycin, lividomycin A, and butirosin B, coupled with the inactivation of these antibiotics in the presence of ATP, suggested enzymatic phosphorylation. This was documented by the transfer of the γ-phosphate of [γ- 32 P]ATP. In contrast, the inability to inactivate gentamicin or tobramycin by the crude enzyme extracts in the presence of ATP suggests another enzymatic mechanism of resistance for these antibiotics, such as adenylation or acetylation. Of importance is the fact that amikacin, a semisynthetic analogue of kanamycin A which is resistant to inactivation by most resistance transfer factor enzymes, was found to inhibit the growth of P. stuartii at low concentrations.

Drug Resistance in Bacteria, Fungi, Malaria, and Cancer

“…Amikacin, gentamicin, kanamycin, streptomycin and tobramycin are some examples and most effective in treatment of gram-negative and gram-positive (Marengo et al 1974;Araoz et al 2000;Chesneau et al 2007). Chemically these contain an amino sugar attached to the aminocyclitol.…”