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BACTERIAL RESPONSE TO OXIDATIVE STRESS INTRODUCTION Oxidative stress (OS) is the term applied when oxidants outnumber antioxidants. The reaction between ferrous (iron), and oxygen results in the formation of harmful superoxide and hydroxyl radicals, which affect all macromolecules. Reactive oxygen species (ROS) represent the collection of number of molecules and free radicals derived from molecular oxygen in addition, there is another class of free radicals that is RNS. Excessive generation of ROS, which damages cells, tissues and organs. Highly reactive radicals cause the oxidative damage of different macromolecules proteins, DNA, and lipids. The sources of ROS are as follows: smoking, herbicides, pesticides, fried foods as well as industrial contaminants that are widespread in soils and on the surfaces of plants. STRESS RESPONSE A global response induces an adaptive metabolism including • ROS elimination, • The bypass of injured pathways, • Reparation of oxidative damages. • Maintenance of reducing power. Living organisms have to build up mechanisms to protect themselves against oxidative stress, with enzymes such as catalase and superoxide dismutase. The toxic forms of oxygen include Hydroxyl radical, Superoxide radical & Hydrogen peroxide. There does not exist any mechanism to detoxify hydroxyl radicals formed by H2O2. The enzyme SOD converts superoxide to H2O2 and O2 catalase converts and H2O2 to water and oxygen. The redox cycling reagents like methyl viologen accepts an electron from NADPH or NADH which lead to synthesis of proteins used in protection. Examples of enzymes induced in E.coli are Mn2 superoxide dismutase , endonuclease IV. GENETIC FACTORS Bacterial genetic responses to oxidative stress are controlled by two major transcriptional factors viz.,OxyR and SoxRS. Peroxide and superoxide are the two major active oxygen species. PEROXIDE RESPONSE Oxy R is a homotetramer , its activated form has an disulfide bond between two cysteine residues OxyR is a transcriptional activator for genes like katG. helps in reorganization of metabolism under stress conditions. SUPEROXIDE RESPONSE Sox R is an iron sulfide protein. Activated SoxR then activates SoxS protein which activates transcription of target genes. Examples of activated genes are sodA (codes for Mn2 superoxide dismutase),nfo(codes for endonuclease IV). THIOREDOXINS AND GLUTAREDOXINS PLAY AN ROLE IN REDUCING DISULFIDE BONDS IN OxyR AND OTHER PROTEINS IN CYTOPLASM They reduce the disulfide bonds in proteins to sulfhydryl groups. They have pairs of cysteine residues separated by two amino acids. Reduced thioredoxin is regenerated by NADPH and reduced glutaredoxin by reduced glutathione DEFENCE MECHANISMS Defence mechanism either keep the concentration of the O2-derived radicals at acceptable levels or repaired oxidative damages. Iron plays a significant role in biology. Some examples of bacterial defences are: 1)Metal chelators- e.g.,metallothionine,ferretin. 2)Low molecular weight compounds and antioxidant enzymes e.g., SOD, catalase. 3) DNA repair systems protein repair system lipid repair system e.g., methionine , sulfoxide reductase. CYTOCHROME OXIDASE BD Cytochrome bd oxygen reductase from Escherichia coli has three hemes, b558,b595 and d. The enzyme is found only in prokaryotes and may serve other important physiological functions. The protective role of cytochrome bd against H2O2 stress is corroborated by the information that the E.coli mutants unable to synthesize the bd oxidase are sensitive to H2O2 and that expression of cytochrome bd increases in the presence of external H2O2. Some other defences of bacteria against oxidative stress 1) In E.coli BtuE peroxidase protects the bacterium against oxidative stress that is generated by tellurite and by other reactive oxygen species. Cells overexpressing BtuE exhibited increased resistance to compounds whose toxicity involves ROS generation. 2)Simultaneous expression of NOD2 and DUOX-2 was found to result in co-operative protection against bacterial cyto-invasion. ROS production and protein & lipid modification induced by ROS have been seen in Crohn's disease. 3)NADPH homeostasis plays an important role in proper execution of soxRS response . NADPH oxidation by ferrodoxin or by the NADPH diaphorase led to significant soxS accumulation in anaerobiosis, and no superoxide forms. 4) The tRNA upregulation increases the survival of E.coli under harsh oxidative stress. At a sub -MIC concentration of ciprofloxacin , tRNA augmented bacteria grew significantly faster than control cells, thereby providing the bacteria with elevated tRNA concentrations a survival advantage in presence of antibiotic. CONCLUSION Oxidative stress (OS) is the term applied when oxidants outnumber antioxidants. Reactive oxygen species (ROS), are hydroxyl radicals (OH) , hydrogen peroxide (H2O2), superoxide radicals. Regulation of oxidation response in bacteria involving OxyR and SoxRS regulons. Heavy metal pollution is a serious problem worldwide there is a growing need to elucidate its toxic effects in a sensitive microorganism. Excessive ROS formation leads to tissue destruction ultimately resulting in inflammatory disorders. Thus the study can be helpful in treatment of diseases in medical field. Recent work has demonstrated that ROS have a role in cell signalling, including; apoptosis; gene expression; and the activation of cell signalling cascades. It should be noted that ROS can serve as both intra- and intercellular messengers. REFERENCES Adriana R. Krapp , Maria Victoria Humbert , and Nestor carrillo;The soxRS response of Escherichia coli can be induced in the absence of oxidative stress and oxygen modulation of NAdph content;2010; SGM journals. Felipe A. Arenas, Paulo C. Covarrubias, Juan M. SAndoval, Jose M. Perez-donoso , James A. Imlay, Claudio C . Vasquez;The Escherichia coli BtuE protein functions as a resistance determinant against reactive oxygen species;volume 6 ,2011;PLOS ONE. Jiayong Zhong, Chuanle Xiao ,Wei Gu, Gaofei Du , Xuesong Sun , Qing-Yu he , Gong Zhang;Transfer Rnas mediate the rapid adaptation of Escherichia coli to oxidative stress ;2015; PLOS genetics. Simone lipinski, Andreas Till, Christian Sina , Alexander Arit, Helmut Grasberger, Stefan Schreiber and Philip Rosenstiel; DUOX2-derived reactive oxygen species are effectors of NOD2-mediated antibacterial responses;2009; Journal of cell science. Vitaliy B. borisov , Elena forte, Albert Davletshin , Daniela Mastronicola, Paolo Sarti, Alessandro Giuffre;Cytochrome bd oxidase r from Escherichia Coli displays Hgh Catalase activity:An additional defense against oxidative stress;2013;Elsevier B.V.