scholarly journals On the mode of action of pseudomonic acid: Inhibition of protein synthesis in Staphylococcus aureus.

1978 ◽  
Vol 31 (4) ◽  
pp. 330-335 ◽  
Author(s):  
JULIA HUGHES ◽  
GRAHAM MELLOWS
Keyword(s):  
Staphylococcus Aureus ◽  
Protein Synthesis ◽  
Mode Of Action ◽  
Acid Inhibition ◽  
Inhibition Of Protein Synthesis ◽  
Pseudomonic Acid

scholarly journals Investigations of the Mode of Action and Resistance Development of Cadazolid, a New Antibiotic for Treatment of Clostridium difficile Infections

2013 ◽  
Vol 58 (2) ◽  
pp. 901-908 ◽  
Author(s):  
Hans H. Locher ◽  
Patrick Caspers ◽  
Thierry Bruyère ◽  
Susanne Schroeder ◽  
Philippe Pfaff ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Clostridium Difficile ◽  
Dna Synthesis ◽  
Mode Of Action ◽  
Cross Resistance ◽  
Resistance Development ◽  
Content Type ◽  
Inhibition Of Protein Synthesis ◽  
Inhibitor Of Protein Synthesis ◽  
Inhibition Of Dna Synthesis

ABSTRACTCadazolid is a new oxazolidinone-type antibiotic currently in clinical development for the treatment ofClostridium difficile-associated diarrhea. Here, we report investigations on the mode of action and the propensity for spontaneous resistance development inC. difficilestrains. Macromolecular labeling experiments indicated that cadazolid acts as a potent inhibitor of protein synthesis, while inhibition of DNA synthesis was also observed, albeit only at substantially higher concentrations of the drug. Strong inhibition of protein synthesis was also obtained in strains resistant to linezolid, in agreement with low MICs against such strains. Inhibition of protein synthesis was confirmed in coupled transcription/translation assays using extracts from differentC. difficilestrains, including strains resistant to linezolid, while inhibitory effects in DNA topoisomerase assays were weak or not detectable under the assay conditions. Spontaneous resistance frequencies of cadazolid were low in all strains tested (generally <10−10at 2× to 4× the MIC), and in multiple-passage experiments (up to 13 passages) MICs did not significantly increase. Furthermore, no cross-resistance was observed, as cadazolid retained potent activity against strains resistant or nonsusceptible to linezolid, fluoroquinolones, and the new antibiotic fidaxomicin. In conclusion, the data presented here indicate that cadazolid acts primarily by inhibition of protein synthesis, with weak inhibition of DNA synthesis as a potential second mode of action, and suggest a low potential for spontaneous resistance development.

scholarly journals STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN

1964 ◽  
Vol 120 (6) ◽  
pp. 1007-1018 ◽  
Author(s):  
R. J. Collier ◽  
A. M. Pappenheimer
Keyword(s):  
Protein Synthesis ◽  
Energy Metabolism ◽  
Hela Cells ◽  
Mode Of Action ◽  
Diphtheria Toxin ◽  
Inhibition Of Protein Synthesis ◽  
Significant Change ◽  
Hexose Phosphates

Intracellular levels of ATP, GTP, and hexose phosphates have been determined in HeLa cells at intervals after exposure to saturating doses of diphtheria toxin. Toxin causes no significant change in the level of any of these phosphorylated intermediates either in the presence or absence of glucose over a period of at least 5 to 6 hours. It is concluded that the inhibition of protein synthesis which occurs in HeLa cells at about 2 hours after the addition of saturating doses of toxin, does not result from an effect of toxin on energy metabolism.

scholarly journals STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN

1966 ◽  
Vol 124 (6) ◽  
pp. 1107-1122 ◽  
Author(s):  
Peter F. Bonventre ◽  
John G. Imhoff
Keyword(s):  
Protein Synthesis ◽  
Mode Of Action ◽  
Protein Turnover ◽  
Diphtheria Toxin ◽  
Clinical Evidence ◽  
Metabolic Effect ◽  
Mammalian Host ◽  
Heart Lesion ◽  
Inhibition Of Protein Synthesis

The effect of crystalline diphtheria toxin on protein synthesis in vivo was evaluated in guinea pigs and mice. By two independent methods of analysis (microdensitometry of tissue radioautograms and radioactivity of tissue proteins), it was established that inhibition of protein synthesis was not a widespread metabolic effect of diphtheria toxin. In the sensitive guinea pig, only the heart and the pancreas showed any demonstrable reduction in the quantity of tritiated leucine incorporated into proteins following challenge of the animals with the crystalline toxin. No such inhibition was noted in mice which are resistant to the action of diphtheria toxin. The effect on the pancreas involved a decrease in the synthesis of pancreatic enzymes and their subsequent secretion. For reasons discussed, it was concluded that this lesion was not as significant as the inhibition of protein synthesis in the heart tissues. Although the rate of protein turnover in heart muscle is relatively low, an inhibition of 73% was noted when the exchange period with the tritiated leucine was 6 hr. It was suggested that the inhibition of protein synthesis in heart tissues could provide a biochemical rationale for the site and mode of action of diphtheria toxin in the sensitive mammalian host. An attempt was also made to correlate the biochemical heart lesion described here with past clinical evidence of cardiac failure and tissue pathology noted in many cases of fatal diphtheria infections of humans.

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