The biological cost of antibiotic resistance.

The frequency and rates of ascent and dissemination of antibiotic resistance in bacterial populations are anticipated to be directly related to the volume of antibiotic use and inversely related to the cost that resistance imposes on the fitness of bacteria. The data available from recent laboratory studies suggest that most, but not all, resistance-determining mutations and accessory elements engender some fitness cost, but those costs are likely to be ameliorated by subsequent evolution.     

Structural origins of gentamicin antibiotic action.

Aminoglycoside antibiotics that bind to the ribosomal A site cause misreading of the genetic code and inhibit translocation. The clinically important aminoglycoside, gentamicin C, is a mixture of three components. Binding of each gentamicin component to the ribosome and to a model RNA oligonucleotide was studied biochemically and the structure of the RNA complexed to gentamicin C1a was solved using magnetic resonance nuclear spectroscopy. Gentamicin C1a binds in the major groove of the RNA. Rings I and II of gentamicin direct specific RNA-drug interactions. Ring III of gentamicin, which distinguishes this subclass of aminoglycosides, also directs specific RNA interactions with conserved base pairs. The structure leads to a general model for specific ribosome recognition by aminoglycoside antibiotics and a possible mechanism for translational inhibition and miscoding. This study provides a structural rationale for chemical synthesis of novel aminoglycosides.     

Mechanism of the antibiotic action pyocyanine.

Exposure of Escherichia coli growing in a rich medium to pyocyanine resulted in increased intracellular levels of superoxide dismutase and of catalase. When these adaptive enzyme syntheses were prevented by nutritional paucity, the toxic action of pyocyanine was augmented. The antibiotic action of pyocyanine was dependent upon oxygen and was diminished by superoxide dismutase and by catalase, added to the suspending medium. Pyocyanine slightly augmented the respiration of E. coli suspended in a rich medium, but greatly increased the cyanide-resistant respiration. Pyocyanine was able to cause the oxidation of reduced nicotinamide adenine dinucleotide, with O2- production, in the absence of enzymatic catalysis. It is concluded that pyocyanine diverts electron flow and thus increases the production of O2- and H2O2 and that the antibiotic action of this pigment is largely a reflection of the toxicity of these products of oxygen reduction.     

Kinetic theory of antibiotic ion carrier. 3

Ion selectivity of ionophorous antibiotics has been measured in many equilibrium experiments such as solvent extraction, electric potential and conductance across an artificial bilayer membrane. However in general these measurements cannot be interpreted as the ion selectivity in a non-equilibrium transporting state which is typically the state of a biological system. This point is explained in this paper based on the simple kinetic theories presented in the preceding papers (Huang, 1971a, Huang, 1971b). The exceptional case of the Eyring model and the Eisenman-Ciani-Szabo model is discussed.It is also found that if the no one-ion-exchange assumption in the theory for the valinomycin-type antibiotics (Huang, 1971b) is relaxed such that the antibiotic S reacts with cation I⁺ and anion X^? in the following way I⁺ + S ? IS⁺, X^? + IS⁺ ? ISX, then the previous equation of cation transport remains unchanged while no simple equation can be written for the anion transport.