Effects of steroidal diamines on DNA duplication and mutagenesis.

Mahler, Henry R.; Baylor, Martha B.

doi:10.1073/pnas.58.1.256

Cited by 25 publications

(4 citation statements)

References 7 publications

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“…The apparent inconsistency in the relationship between the extent of killing by colicins and their physiological effects, and the results obtained with the steroid, have prompted a closer examination of three aspects of colicin K action: (i) the relationship between the fraction of cells killed and the fraction which retain potassium, (ii) the relationship between multiplicity and the initial rate of potassium loss, and (iii) the effect of temperature on the initial rate of potassium loss. The results are consistent with the conclu- 10 sions drawn from single-hit killing, and have revealed a delay in the initiation of potassium 9loss following colicin adsorption at low temperature. The fraction of cells killed and the fraction of total radiopotassium lost by 10 minutes are shown.…”

supporting

confidence: 88%

Mechanism of Colicin Action: Early Events

Wendt

1970

J Bacteriol

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The kinetics and the temperature dependence of potassium loss from Escherichia coli cells treated with colicin K have been examined. At 37 C, after a single lethal hit, essentially all of the intracellular potassium is lost within the first few minutes of treatment. The initial rate of loss is linearly related to colicin concentration up to a multiplicity of 30. As the temperature is decreased over the range from 37 to 1 C, an increasing delay is seen in the initiation of potassium loss after colicin adsorption. This delay can be overcome by increasing colicin multiplicity and probably reflects an alteration of the cell membrane at these temperatures. A comparison of this effect with an apparently related effect of temperature on the action of irehdiamine A indicates that the delay may represent the inhibition of a transmission process occurring in the membrane.Colicin K is one of three colicins known to inhibit many energy-dependent processes in Escherichia coil (2,4,12,16) and has been previously shown to inhibit active transport of potassium and to cause the loss of intracellular potassium (17). These effects apparently occur by a direct action on the cell membrane (2) and have been assumed to result from changes which are transmitted over or through the membrane from a local site of action (9,15,16). A physical model which could acc'ount for the possible spreading of the local action of a single colicin molecule has been proposed (3,4). This model supposes that conformational changes may be propagated between membrane subunits in much the same manner as linked subunits of allosteric enzymes respond to the binding of a ligand molecule to one of the units (cooperativity within the membrane).The major evidence for a transmission of the local action of a single colicin molecule seems to be the single-hit killing shown by colicins. The conclusion has been drawn from single-hit killing that a cell attacked by a single colicin molecule has a definite probability of being killed (9,15,16), and this in turn implies that the effect of the single molecule can be transmitted to the whole cell. On this basis it might be expected that the effect of a single lethal unit on a cell should be demonstrable at the level of the affected process as well as at the level of cell killing. That is, at low multiplicities the fraction of the cell population which received single lethal hits should be correlated with the fraction of which the metabolism was blocked. In experimental systems for which data on this point are available, the relationship is not clear. The effects of colicins E2 and E3 are very slow to appear and require high multiplicities before deoxyribonucleic acid or protein synthesis are markedly affected (7,15,17). At low multiplicities (which are still sufficient to kill 95% of the cells), the effects are only slight. The effects of colicins K or El are quite rapid, but the fraction of cells killed is generally greater than the extent of inhibition (5, 6).Another conclusion from the single-hit killing has been that of ...

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supporting

confidence: 88%

Mechanism of Colicin Action: Early Events

Wendt

1970

J Bacteriol

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“…GA3 is known to regulate de novo amylase production during seed germination (Chrispeels and Varner, 1976). Here it is relevant to note that nucleic acid metabolism and protein synthesis studied in bacteria and animals are known to be variously affected by different alkaloids (Grollman, 1967;Mahler and Baylor, 1967;Perlman and Penman, 1970;Robinson, 1974;Jimnez et al, 1975). Alternatively, the alkaloid could affect either the catalytic properties of the enzyme or its biosynthesis, or both.…”

Section: Possible Mode Of Action Of 137-tmentioning

confidence: 99%

Allelopathy

1992

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“…In addition to the evidence for IDA binding ith 10-4 M to polynucleotides in vitro, the principle basis the recov-for Mahler and Baylor's (15) conclusion that in at 25 C, there is a direct effect of IDA on DNA is the ability to observation that, in phage-infected cells, phagefe of about directed DNA synthesis is more sensitive to ,s were ap-inhibition by IDA than is phage-directed RNA I the initial or protein synthesis. However, in uninfected roximately cells, the syntheses of DNA, RNA, and proteins a-and ex-are about equally sensitive to IDA (15), and the to 25-min growth of the RNA-containing virus MS2 is ecovery of only slightly less sensitive to IDA inhibition minutes at 29C FIG.…”

Section: Discussionmentioning

confidence: 99%

“…Mahler and Baylor (15) recently described the inhibitory actions of the steroidal diamines irehdiamine A (IDA) and malouetine (MAL) on the growth of bacteriophage T2 in infected cells of Escherichia coli. Bacteriophage-directed deoxyribonucleic acid (DNA) synthesis is more sensitive to steroidal diamine inhibition than ribonucleic acid (RNA) or protein synthesis, and Mahler and Baylor (15) proposed that DNA is the primary target of steroidal diamine action. Because of the well-known interactions of polyamines and steroids with biological membranes (1,18,20,26,28) and because of our own interest in virus and chemically induced changes in the bacterial cell membrane (23-25), we have looked at the effects of steroidal diamines on cell permeability and active transport.…”

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confidence: 99%

Action of Steroidal Diamines on Active Transport and Permeability Properties of Escherichia coli

Silver

Levine

1968

J Bacteriol

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The steroidal diamine irehdiamine A (IDA) is a potent inhibitor of bacteriophage growth and macromolecular synthesis in Escherichia coli. By using radioactive 42K and "4C-thiomethylgalactoside (TMG), rapid effects of IDA and related steroids, both on the influx of potassium and TMG via their respective transport systems and on the efflux (leakage) of radioactivity from the treated cells, have been measured. IDA affects both the influx and efflux of 42K at concentrations of steroid as low as 2 x 10-I M. Because of the increased leakage, it is not possible to tell whether there is a direct effect reducing the rate of active transport of potassium. The primary diamine, IDA, and its bis-secondary, bis-tertiary, and bis-quaternary diamine analogues are decreasingly effective in altering cell permeability properties in the order 10 > 20 > 30 > 4°. The effects of IDA on potassium transport are mirrored by similar effects on the transport of TMG. Therefore, the action of IDA is on the cell membrane and not directly on one or another transport system. The effects of IDA on cell permeability can reasonably explain the inhibitory actions of the drugs on bacteriophage growth and cellular metabolism.

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Effects of steroidal diamines on DNA duplication and mutagenesis.

Cited by 25 publications

References 7 publications

Mechanism of Colicin Action: Early Events

Mechanism of Colicin Action: Early Events

Allelopathy

Action of Steroidal Diamines on Active Transport and Permeability Properties of Escherichia coli

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