1区 · 综合性期刊
Article
作者: Licata, L. ; Barrett, J. F. ; Klaubert, D. H. ; Frosco, M. B. ; Lawrence, L. E. ; Hoch, J. A. ; Chen, R. ; Fernandez, J. ; Foleno, B. ; Ohemeng, K. ; Whiteley, J. M. ; Hlasta, D. J. ; Wang, L. ; Johnson, S. ; Donetz, A. ; Huang, S. ; Macielag, M. J. ; Goldschmidt, R. M. ; Bernstein, J. ; Demers, J. P. ; Frechette, R. ; Kanojia, R.
A class of antibacterials has been discovered that inhibits the growth of Gram-positive pathogenic bacteria. RWJ-49815, a representative of a family of hydrophobic tyramines, in addition to being a potent bactericidal Gram-positive antibacterial, inhibits the autophosphorylation of kinase A of the KinA∷Spo0F two-component signal transduction system
in vitro
. Analogs of RWJ-49815 vary greatly in their ability to inhibit growth of bacteria and this ability correlates directly with their activity as kinase A inhibitors. Compared with the potent quinolone, ciprofloxacin, RWJ-49815 exhibits reduced resistance emergence in a laboratory passage experiment. Inhibition of the histidine protein kinase∷response regulator two-component signal transduction pathways may present an opportunity to depress chromosomal resistance emergence by targeting multiple proteins with a single inhibitor in a single bacterium. Such inhibitors may represent a class of antibacterials that potentially may represent a breakthrough in antibacterial therapy.
