Marie-Louise Capmau

New Plasmid-Mediated Nucleotidylation of Aminoglycoside Antibiotics in Staphylococcus aureus

A wild-type strain of Staphylococcus aureus, which inactivates a wide variety of aminoglycosides (except the gentamicin components), has been found to harbor a plasmid (RAp01) that mediates the biosynthesis of a nucleotidyltransferase. This enzyme modifies the 4′-hydroxy function of these antibiotics. The plasmid has been studied, the enzyme responsible for this resistance pattern has been isolated by affinity chromatography, and its kinetics and physicochemistry have been characterized. The target of this enzyme has also been located by demonstrating the structure of one inactivated compound, 4′-(O)-adenylyltobramycin.

2″-O-Phosphorylation of Gentamicin Components by a Staphylococcus aureus Strain Carrying a Plasmid

A wild-type strain of Staphylococcus aureus that inactivates the 4,6-glycosidically linked deoxystreptamine aminoglycoside antibiotics by a plasmid-mediated process was found to harbor two enzymes: an acetyltransferase of the AAC(6′) type and a new phosphotranferase specific to the gentamicin components. The target of this last enzyme is the 2″-hydroxyl function of these antibiotics, since one inactivated compound is 2″-(O)-phosphorylsisomicin.

Inhibitors of GDP-mannose dehydrogenase of Pseudomonas aeruginosa mucoid strains

Abstract The synthesis of 5′-amino-5′-deoxy guanosine was improved in order to use it for elaboration of liposolubles GDP-mannose analogues. GDP-mannose is the substrate of GDP-mannose dehydrogenase, a key enzyme in the alginates biosynthetic pathway of Pseudomonas aeruginosa mucoid strains. Guanosine, 5′-amino-5′-deoxy-guanosine, 5′-(3-hydroxypropyl)-amino-5′-deoxy-guanosine and 2 GDP mannose analogues were tested on the GDP mannose dehydrogenase activity. The more potent inhibitor was the GDP-mannose analogue where mannose is substituted by a 6-ethynyl derivative, linked to an N 2 -acetyl-2′,3′- O -isopropylidene guanosine by a sulfonyl amino carbonyl arm. As a hypothesis, this compound could be a suicide or irreversible inhibitor for the enzyme