Cell cycle arrest in archaea by the hypusination inhibitor N(1)-guanyl-1,7-diaminoheptane - PubMed (original) (raw)

Cell cycle arrest in archaea by the hypusination inhibitor N(1)-guanyl-1,7-diaminoheptane

B P Jansson et al. J Bacteriol. 2000 Feb.

Abstract

Hypusination is an essential posttranslational modification unique to archaeal and eukaryotic protein synthesis initiation factor 5A (aIF5A and eIF5A, respectively). We have investigated the effect of the efficient hypusination inhibitor N(1)-guanyl-1,7-diaminoheptane (GC(7)) on four archaeal and one bacterial species. We found that (i) archaea are sensitive to GC(7), whereas the bacterium Escherichia coli is not, (ii) GC(7) causes rapid and reversible arrest of growth of the archaeon Sulfolobus acidocaldarius, and (iii) the growth arrest is accompanied by a specific reversible arrest of the cell cycle prior to cell division. Our findings establish a link between hypusination and sustained growth of archaea and thereby provide the framework to study molecular details of archaeal cell cycle in connection with in vivo functions of hypusine and of aIF5A and eIF5A.

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Figures

FIG. 1

FIG. 1

(A) Dose-dependent inhibition of S. acidocaldarius growth by GC7. S. acidocaldarius was subjected to 0 (⧫), 50 (□), 100 (▴), 200 (×), 350 (▵), 500 (●), and 1,000 (+) μM concentrations of GC7. Growth was monitored by OD600 measurements at the indicated time points. The growth curves give approximate doubling times of 3.5 h (0 μM GC7), 4.5 h (50), 8.0 h (100), 20 h (200), 25 h (350), and 50 h (500), whereas no growth could be detected at 1,000 μM GC7. (B) Analysis of GC7 effects on the S. acidocaldarius cell cycle. Samples were taken every 15 min after addition of GC7 (200 μM), fixed in ethanol, stained with mithramycin and ethidium bromide, and analyzed by flow cytometry. The left column represents the light scatter (cell size), and the right column represents the fluorescence (DNA content) of the cell population from the same samples. (C) The effect by GC7 is cytostatic. S. acidocaldarius resumed normal cell growth (i), including cell division and replication (ii), after reduction of the GC7 concentration to noneffective levels. S. acidocaldarius cells were treated with 200 μM GC7 or left untreated, and the drug was removed after 4 h. The release was accomplished either by dilution (○ and ■) or by change of medium after centrifugation (▴ and ×). (i) Growth curves were determined by OD600 measurements. The treated cultures (■ and ×) were compared to untreated cultures (○ and ▴). (ii) Flow cytometric analysis of samples fixed in ethanol every 15 min after release by dilution (samples correspond to treated culture dilution curve [■] in graph i).

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