title: Biochemical mechanisms of antibiotic resistance in a clinical isolate of Mycobacterium fortuitum. Presence of beta-lactamase and aminoglycoside-acetyltransferase and possible participation of altered drug transport on the resistance mechanism.
abstract: Mycobacterium fortuitum was isolated from specimens of bone marrow from a patient with chronic osteomyelitis. This isolate was resistant to most antimycobacterial drugs, aminoglycosides, and beta-lactam antibiotics. Cell-free extracts from the clinical isolate contained an aminoglycoside acetyltransferase and beta-lactamase. On the basis of substrate specificity, the former enzyme was identified as the acetyltransferase (3), subtype III or IV. However, no positive correlation could be observed between resistance levels (minimal inhibitory concentrations) and the degree of inactivation of aminoglycosides. In vitro, the enzyme reaction required 40 to 60 min to completely inactivate kanamycin. Protein synthesis by ribosomes prepared from this clinical isolate was inhibited by one tenth the concentration of aminoglycosides required to inhibit growth of whole cells. These results suggest that some crypticity factor(s), such as the decreased permeability of drugs, may participate in the intrinsic resistance of the organism.
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D001696:Biomechanical Phenomena; D004352:Drug Resistance, Microbial; D005796:Genes; D006801:Humans; D007700:Kinetics; D009161:Mycobacterium / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D009994:Osmolar Concentration; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase; D001618:beta-Lactamases