Failure of aminoglycoside antibiotics to kill anaerobic, low-pH, and resistant cultures.
The critical inhibition of ribosome function by aminoglycosides has long been established. But the binding of drug to ribosomes is reversible: why then are aminoglycosides bactericidal? Several groups have shown that irreversible action (lethality) results from irreversible uptake into susceptible cells; conversely, resistance in cases such as anaerobiosis is associated with the failure of uptake. Oddly, the pattern of results excludes all traditional transport mechanisms; most unusual is the apparent dependence of uptake on the interaction of drug with ribosomes. A traditional view that ribosomes may function during uptake as a "sink" for aminoglycosides cannot explain all the data. Instead, the alternative is considered that cycling ribosomes at the cell membrane help to induce "one-way endocytic pores." Although no detailed mechanism is formulated, the results do suggest a way that the permeation of antibiotics might be systematically controllable to render them more cidal.
Schlessinger
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Department of Microbiology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110.
D000693:Anaerobiosis; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D001693:Biological Transport, Active; D004352:Drug Resistance, Microbial; D006863:Hydrogen-Ion Concentration; D013307:Streptomycin / Q000493:pharmacokinetics / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D013307:Streptomycin