Pilar Gutiérrez Navarro⁽¹⁾, Iluminada Hernández⁽²⁾, Pedro Martínez de las Parras⁽³⁾, Abdelkrim El Bekkouri⁽⁴⁾, Raquel García^(5)
(1)Facultad de Farmacia. Universidad de Granada. - Granada. Spain
⁽²⁾Departamento de Química Física.. Universidad de Granada - Granada. Spain
⁽³⁾Dpto. Química Física. Universidad de Granada - Granada. Spain
⁽⁴⁾⁽⁵⁾Dpto. Quimica Fisica. Universidad de Granada - Granada. Spain

		[Biophysics]
	[Biochemistry]

INTRODUCTION

Bacterial resistence to the ß - lactam antibiotics is atributted to the presence of a family of enzymes, the ß -lactamases, that render the antibiotic inactive by hydrolyzing the C-N bond. The enzimes have been grouped into four classes^(1,2) Classes A, C and D use an active site serine as a nucleophile. Class B ß - lactamases employ metal ions ( Zn [II], Cd [II], Co[II] or Mn[II] ) ^(3,4) ; Zn [II] or Cd [II] ⁽⁵⁾ ; one or two zinc ions ⁽⁶⁾ to effect ß - lactam cleavage. There are no clinically useful inhibitors of these metallo-enzymes , although the metal chelators EDTA and 1,10-o-phenantroline, and some mercurial chelators have shown inhibitory activity in vitro⁽⁷⁾. Recently, a series of mercaptoacetic acid thiol esters and the saicyloyl cyclic phosphate have been shown to inhibit some of the metalloenzymes ^(8,9) . Therefore, at the moment, there is not specific inhibitors useful in therapeutical treatment because of the mechanism of action of the enzymes remains still unclear. The estudies currently devoted to the metalloenzymes are focused on the interaction between the enzyme and the metal ion in order to establish the role of the different metal ions in the catalytic activity ^(10,11).

The class B ß - lactamases have initilly received little attention because this class of enzymes was produced by only relatively innocuous Bacillus cereus strains. More recently, identification of some zinc ß -lactamase producing pathogenic strains of Bacteroides fragilis, Aeromonas, Serratia, Stenotrophomonas has increased the interest for this class of enzymes ⁽¹⁰⁾. The fact that metalloenzymes hydrolyse almost all ß - lactam antibiotics , including carbapenems and that they are not sensitive to dthe classical ß - lactamase inhibitors has increased enormously the interest for this class of enzymes ⁽¹⁰⁾.

Taking into account the interest of the interaction of the metal ion with the antibiotic, we have carried out a kinetic study of the degradation of a ß - lactam antibiotic , ampicillin, in the presence of those metal ions which are related to the metalloenzymes. Absorption and fluorescence data have been used to monitor the antibiotic decomposition reaction allowing us to obtain the kinetic equation.

Discussion Board

Any Comment to this presentation?

[ABSTRACT] [INTRODUCTION] [EXPERIMENTAL] [RESULTS AND DISCUSSION] [FIGURES] [FIGURES-2] [REFERENCES] [Discussion Board]

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		[Biophysics]
	[Biochemistry]

Pilar Gutiérrez Navarro, Iluminada Hernández, Pedro Martínez de las Parras, Abdelkrim El Bekkouri, Raquel García
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Last update: 11/02/00