MODES OF ACTION OF ANTIBIOTICS 



101 



H. injiucnzac from streptomycin sensitivity 

 to streptomycin resistance when it is added 

 to high concentrations of transformhig DXA 

 from a resistant strain. 



Kersten (1961) recently reported on the 

 inhibition of the growth inhibiting effect 

 of actinomycin upon Ncurospora crassa 

 and Streptococcus faecalis l)y DNA, RNA, 

 and some of their degradation products 

 (purine moieties). The binding of actino- 

 mycin and nucleic acids was demonstrated 

 l)y changes in the ahsorption of spectra of 

 actinomycin. 



The effect of actinomycin upon the ana- 

 erobic carbohydrate metabolism of Candida 

 albicans has been studied l)y l^rave (1959). 



Azasenne and DON 



Azaserine (o-diazoacetyl-L-serine) and 

 DON (6-diazo-5-oxo-L-norleucine) inhibit 

 the growth of E. coli in a synthetic medium. 

 They interfere with the incorporation of gly- 

 cine and formate, y)ut not of adenine, into nu- 

 cleic acids. According to Levenberg et al. 

 (1957), they interfere with the biosynthesis 

 of inosinic acid, behaving as competitive in- 

 hibitors of glutamine. The action of DON 

 upon the growth of E. coli, unlike that of aza- 

 serine, is not antagonized by adenine, gua- 

 nine, hypoxanthine, and the corresponding 

 nucleosides (Aiaxwell and Nickel, 1957). 



Chain (1958) also demonstrated that aza- 

 serine interferes with the synthesis of the 

 purine ring system, thus affecting the forma- 

 tion of nucleotide. In the synthesis of ino- 

 sinic acid by cell-free pigeon liver extracts, 

 azaserine inhibits the formation of formyl- 

 glycinamide-ribotide and glutamine (in the 

 presence of adenosine triphosphate), appar- 

 ently acting as a specific antimetabolite to 

 glutamine, to which it is structurally related. 



The amoebicidal action of azaserine was 

 investigated by Nakamura (1956). 



Polijenes 



Among the antifungal agents, nystatin, a 

 polyene antibiotic, has received the greatest 



attention. This is a tetraene compound with 

 a diene unit, a carbonyl, and a primary 

 amino group. It inhibits the growth of most 

 fungi, in concentration of 1 to 10 /ig per ml, 

 but has no effect upon actinomycetes, bac- 

 teria, and rickettsiae. It is more effective 

 upon the mycelium than upon the spores of 

 the fungi. It is primarily fungicidal and its 

 action is irreversible. According to Lampen 

 et ol. (1957), nystatin inhil)its the endoge- 

 nous respiration and the aerobic and anaero- 

 bic utilization of glucose and certain other 

 carbon sources by yeasts and other fungi. 

 Low levels of the antibiotic show increased 

 oxygen consumption; high levels show an 

 initial stimulation, followed by abrupt cessa- 

 tion of metabolism, when the cells are no 

 longer viable. Other polyenes (amphotericin) 

 inliil)it glycolysis. Nonpolyene antifungal 

 agents (cycloheximide) have no such effect. 

 The conclusion was reached that nystatin 

 blocks a reaction of general metabolic signifi- 

 cance to fungi. I'urther information on the 

 mode of action of nystatin is found in the 

 work of Sutton et al. (19()0), Marini et al. 

 (1960), Tape et al. (1960), and Horvath and 

 Szentirmai (19()0). 



Drouhet el al. (19C)0) studied the effect of 

 amphotericin B on the growing phase of 

 yeasts. It produces an inhibition of the 

 synthesis of proteins, ribonucleic acid, 

 carbohydrate, and polyphosphate reserves. 

 The disturbance of phosphorus metabolism 

 is related to the stimulation of endogenous 

 or exogenous oxidations. The action of other 

 polyenes on respiration is distinct from that 

 of other antifungal antibiotics such as 

 cycloheximide. Amphotericin B produces an 

 increase in Oo uptake by resting or growing 

 cells of C. albicans in the presence or the 

 absence of carbon substrate. This effect is no 

 longer observed on yeasts which have been 

 washed after contact with the antibiotic. It 

 was suggested that the washing eliminates 

 the products responsible for the increase in 

 O2 uptake, products released by alteration 

 of cell permeability. The mode of action of 



