Inactivation of lincosaminide antibiotics in Staphylococcus. Identification of lincosaminide O-nucleotidyltransferases and comparison of the corresponding resistance genes.
Resistance to lincomycin by inactivation has been detected in numerous clinical isolates of Staphylococcus; in crude extracts of Staphylococcus haemolyticus BM4610 and Staphylococcus aureus BM4611, inactivation of lincomycin and clindamycin requires the presence of a nucleoside 5'-triphosphate (ATP, GTP, CTP, or UTP) as nucleotidyl donor and Mg2+ as cofactor. The biochemical mechanism of lincosaminide inactivation was elucidated by determination of the structure of inactivated lincomycin and clindamycin by physicochemical techniques, including UV absorption spectrophotometry, 31P and 1H nuclear magnetic resonance, and periodate oxidation. In the two strains, inactivation of lincomycin gave rise to lincomycin 3-(5'-adenylate), whereas clindamycin was inactivated through its conversion to clindamycin 4-(5'-adenylate). The gene linA' encoding the 3-lincomycin, 4-clindamycin O-nucleotidyltransferase in S. aureus BM4611 has been sequenced and displays 93% homology with the gene linA encoding the 3-lincomycin, 4-clindamycin O-nucleotidyltransferase found in S. haemolyticus BM4610. The two enzymes are 161 amino acids long and differ by 14 amino acid substitutions.
Brisson-Noël
A
A
Unité des Agents Antibactériens, Centre National de la Recherche Scientifique UA 271, Institut Pasteur, Paris, France.
Delrieu
P
P
Samain
D
D
Courvalin
P
P
D000595:Amino Acid Sequence; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001483:Base Sequence; D004352:Drug Resistance, Microbial / Q000235:genetics; D005796:Genes; D005798:Genes, Bacterial; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009713:Nucleotidyltransferases / Q000378:metabolism*; D011815:R Factors; D015183:Restriction Mapping; D012265:Ribonucleotides / Q000378:metabolism; D013210:Staphylococcus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D013379:Substrate Specificity
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012265:Ribonucleotides; D009713:Nucleotidyltransferases; C057535:lincosaminide O-nucleotidyltransferase