Aminoglycoside resistance mediated by the bifunctional enzyme 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase.
The expression of the bifunctional aminoglycoside inactivating enzyme 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase is the most important mechanism of high-level aminoglycoside resistance in Staphylococcus and Enterococcus. The enzyme is unique because it presents two different aminoglycoside-modifying activities located in different regions of the molecule. The gene aac(6')-aph(2") which encodes the synthesis of the enzyme is present in Tn4100-like transposons which are inserted both in R plasmids and the chromosomes of aminoglycoside-resistant isolates. The genetic structure of aac(6')-aph(2")-containing isolates indicates that their origin is not clonal, but plasmid conjugation together with multiple insertion events are in the basis of the rapid spread of aminoglycoside resistance among Gram-positive bacteria. There is not any prevalent genetic linkage of aac(6')-aph(2") with other antibiotic-resistance determinant. However, most methicillin resistant Staphylococcus strains present also high-level aminoglycoside resistance as the consequence of constant antibiotic pressure. This situation could change in the next future with the reported reemergence of gentamicin-susceptible MRSA isolates. Recent data show that inhibitors of eukaryotic protein kinases inhibit as well the aminoglycoside phosphotransferase activity. This effect indicates a common structure for these two families of proteins and opens the possibility for a meaningful survey of inhibitors of 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase useful in clinical practice.
Culebras
E
E
Servicio de Microbiología, Hospital Clínico San Carlos, Plaza de Cristo Rey s/n, 28048-Madrid, Spain.
Martínez
J L
JL
D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004251:DNA Transposable Elements / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D016983:Enterococcus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D008826:Microbial Sensitivity Tests; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013210:Staphylococcus / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; C108453:6'-aminoglycoside acetyltransferase-2''-aminoglycoside phosphotransferase; D000123:Acetyltransferases; D017853:Phosphotransferases (Alcohol Group Acceptor)