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ÏÂÎç°ÑscienceÉÏ×î½üµÄ3ƪ¹ØÓÚ¿¹ÉúËØÓëros¹ØÏµµÄÎÄÕÂÏÂÔØÁË¡£ÕªÒªÈçÏ£º 1.Killing by bactericidal antibiotics does not depend on reactive oxygen species. Abstract Bactericidal antibiotics kill by modulating their respective targets. This traditional view has been challenged by studies that propose an alternative, unified mechanism of killing, whereby toxic reactive oxygen species (ROS) are produced in the presence of antibiotics. We found no correlation between an individual cell's probability of survival in the presence of antibiotic and its level of ROS. An ROS quencher, thiourea, protected cells from antibiotics present at low concentrations, but the effect was observed under anaerobic conditions as well. There was essentially no difference in survival of bacteria treated with various antibiotics under aerobic or anaerobic conditions. This suggests that ROS do not play a role in killing of bacterial pathogens by antibiotics. 2 Cell death from antibiotics without the involvement of reactive oxygen species. Abstract Recent observations have suggested that classic antibiotics kill bacteria by stimulating the formation of reactive oxygen species (ROS). If true, this notion might guide new strategies to improve antibiotic efficacy. In this study, the model was directly tested. Contrary to the hypothesis, antibiotic treatment did not accelerate the formation of hydrogen peroxide in Escherichia coli and did not elevate intracellular free iron, an essential reactant for the production of lethal damage. Lethality persisted in the absence of oxygen, and DNA repair mutants were not hypersensitive, undermining the idea that toxicity arose from oxidative DNA lesions. We conclude that these antibiotic exposures did not produce ROS and that lethality more likely resulted from the direct inhibition of cell-wall assembly, protein synthesis, and DNA replication. 3. Fe-S cluster biosynthesis controls uptake of aminoglycosides in a ROS-less death pathway. Abstract All bactericidal antibiotics were recently proposed to kill by inducing reactive oxygen species (ROS) production, causing destabilization of iron-sulfur (Fe-S) clusters and generating Fenton chemistry. We find that the ROS response is dispensable upon treatment with bactericidal antibiotics. Furthermore, we demonstrate that Fe-S clusters are required for killing only by aminoglycosides. In contrast to cells, using the major Fe-S cluster biosynthesis machinery, ISC, cells using the alternative machinery, SUF, cannot efficiently mature respiratory complexes I and II, resulting in impendence of the proton motive force (PMF), which is required for bactericidal aminoglycoside uptake. Similarly, during iron limitation, cells become intrinsically resistant to aminoglycosides by switching from ISC to SUF and down-regulating both respiratory complexes. We conclude that Fe-S proteins promote aminoglycoside killing by enabling their uptake µ«Õ⼸ƪÎÄÕ¶¼ÊÇ˵¿¹ÉúËØ¿¹¾ú»úÖÆ¸úϸ¾úÄÚros²úÉúûÓйØÏµ¡£¶øÎÒµÄÏë·¨ÊÇrosÊÇ·ñÄÜÐÖú¿¹ÉúËØ¿¹¾ú£¬ÕâÑùÓ¦¸Ã»¹ÄÜ×ö°É¡£ÇóÖ¸µ¼¡£¡£¡£¡£¡£@Á貨Àö @ixido @Haibara_Ai ˳±ã°Ñ¸½¼þÌùÉϹ©´ó¼Ò½»Á÷ÌÖÂÛ¡£ http://pan.baidu.com/share/link? ... p;amp;uk=4095909806 http://pan.baidu.com/share/link? ... p;amp;uk=4095909806 http://pan.baidu.com/share/link? ... p;amp;uk=4095909806 |
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kx444555: ½ð±Ò+2, ¹ÄÀø½»Á÷ 2013-07-12 13:26:27
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