Bacteria are permanently in contact with reactive oxygen species (ROS), both over the course of their life cycle as well that present in their environment. These species cause damage to proteins, lipids, and nucleotides, negatively impacting the organism. To detect these ROS molecules and to stimulate the expression of proteins involved in antioxidative stress response, bacteria use a number of different protein-based regulatory and sensory systems. ROS-based stress detection mechanisms induce posttranslational modifications, resulting in overall conformational and structural changes within sensory proteins. The subsequent structural rearrangements result in changes of protein activity, which lead to regulated and appropriate response on the transcriptional level. Many bacterial enzymes and regulatory proteins possess a conserved signature, the zinc-containing redox centre Cys-X-X-Cys in which a disulfide bridge is formed upon oxidative stress. Other metal-dependent oxidative modifications of amino acid side-chains (dityrosines, 2-oxo-histidines, or carbonylation) also modulate the activity of redox-sensitive proteins. Using molecular biology, biochemistry, biophysical, and structure biology tools, molecular mechanisms involved in sensing and response to oxidative stress have been elucidated in detail. In this review, we analyze some examples of bacterial redox-sensing proteins involved in antioxidative stress response and focus further on the currently known molecular mechanism of function. 1. Introduction Interference in the balance between the environmental production of reactive oxygen species (ROS), including hydroxyl radicals (?OH) and hydrogen peroxide (H2O2), and the ability of biological systems to readily detect and detoxify them, or repair the resulting damage, are defined as oxidative stress. Highly reactive radicals cause the oxidative damage of different macromolecules—proteins, DNA, and lipids—leading to loss of function, an increased rate of mutagenesis, and ultimately cell death. In humans, for example, oxidative stress is involved in many diseases, such as rheumatoid arthritis, autoinflammatory diseases, neurodegenerative diseases, and cancer [1, 2]. However, the production of some ROS (e.g., ?OH) can also be beneficial, as they are used by the human immune system to attack and kill pathogens, such as the production of ROS by macrophages. Additionally, H2O2 is an important signalling molecule that participates in redox signalling [3]. Sensing of ROS-mediated signals also plays a crucial role in the biology of microorganisms. Bacteria,
References
[1]
L. Montagnier, R. Olivier, and C. Pasquier, Eds., Oxidative Stress in Cancer, AIDS and Neurodegenerative Diseases, Marcel Dekker, New York, NY, USA, 1998.
[2]
P. G. Winyard, D. R. Blake, and C. H. Evans, Eds., Free Radicals and Inflammation, Birkh?user, Basel, Switzerland, 2000.
[3]
H. J. Forman, M. Maiorino, and F. Ursini, “Signaling functions of reactive oxygen species,” Biochemistry, vol. 49, no. 5, pp. 835–842, 2010.
[4]
S. C. Andrews, A. K. Robinson, and F. Rodríguez-Qui?ones, “Bacterial iron homeostasis,” FEMS Microbiology Reviews, vol. 27, no. 2-3, pp. 215–237, 2003.
[5]
G. Rudolph, H. Hennecke, and H. M. Fischer, “Beyond the fur paradigmml: iron-controlled gene expression in rhizobia,” FEMS Microbiology Reviews, vol. 30, no. 4, pp. 631–648, 2006.
[6]
M. A. Kohanski, D. J. Dwyer, B. Hayete, C. A. Lawrence, and J. J. Collins, “A common mechanism of cellular death induced by bactericidal antibiotics,” Cell, vol. 130, no. 5, pp. 797–810, 2007.
[7]
J. Duan and D. L. Kasper, “Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species,” Glycobiology, vol. 21, pp. 401–409, 2011.
[8]
K. Li, S. Hein, W. Zou, and G. Klug, “The glutathione-glutaredoxin system in Rhodobacter capsulatus: part of a complex regulatory network controlling defense against oxidative stress,” Journal of Bacteriology, vol. 186, no. 20, pp. 6800–6808, 2004.
[9]
P. Zou and H. Schrempf, “The heme-independent manganese-peroxidase activity depends on the presence of the C-terminal domain within the Streptomyces reticuli catalase- peroxidase CpeB,” European Journal of Biochemistry, vol. 267, no. 10, pp. 2840–2849, 2000.
[10]
S. J. Stohs and D. Bagchi, “Oxidative mechanisms in the toxicity of metal ions,” Free Radical Biology and Medicine, vol. 18, no. 2, pp. 321–336, 1995.
[11]
K. Hantke, “Bacterial zinc transporters and regulators,” BioMetals, vol. 14, no. 3-4, pp. 239–249, 2001.
[12]
T. M. Bray and W. J. Bettger, “The physiological role of zinc as an antioxidant,” Free Radical Biology and Medicine, vol. 8, no. 3, pp. 281–291, 1990.
[13]
K. F. Smith, L. A. Bibb, M. P. Schmitt, and D. M. Oram, “Regulation and activity of a zinc uptake regulator, zur, in Corynebacterium diphtheriae,” Journal of Bacteriology, vol. 191, no. 5, pp. 1595–1603, 2009.
[14]
D. Ortiz de Orué Lucana, M. Tr?ller, and H. Schrempf, “Amino acid residues involved in reversible thiol formation and zinc ion binding in the Streptomyces reticuli redox regulator FurS,” Molecular Genetics and Genomics, vol. 268, no. 5, pp. 618–627, 2003.
[15]
S. K. Small, S. Puri, and M. R. O'Brian, “Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other Alpha-proteobacteria,” BioMetals, vol. 22, no. 1, pp. 89–97, 2009.
[16]
G. Bogel, H. Schrempf, and D. Ortiz de Orué Lucana, “The heme-binding protein HbpS regulates the activity of the Streptomyces reticuli iron-sensing histidine kinase sens in a redox-dependent manner,” Amino Acids, vol. 37, no. 4, pp. 681–691, 2009.
[17]
D. Ortiz de Orué Lucana and M. R. Groves, “The three-component signalling system HbpS-SenS-SenR as an example of a redox sensing pathway in bacteria,” Amino Acids, vol. 37, no. 3, pp. 479–486, 2009.
[18]
M. P. Schmitt, “Identification of a two-component signal transduction system from Corynebacterium diphtheriae that activates gene expression in response to the presence of heme and hemoglobin,” Journal of Bacteriology, vol. 181, no. 17, pp. 5330–5340, 1999.
[19]
C. Jacob, I. Knight, and P. G. Winyard, “Aspects of the biological redox chemistry of cysteine: from simple redox responses to sophisticated signalling pathways,” Biological Chemistry, vol. 387, no. 10-11, pp. 1385–1397, 2006.
[20]
D. Barford, “The role of cysteine residues as redox-sensitive regulatory switches,” Current Opinion in Structural Biology, vol. 14, no. 6, pp. 679–686, 2004.
[21]
S. Sivaramakrishnan, A. H. Cummings, and K. S. Gates, “Protection of a single-cysteine redox switch from oxidative destruction: on the functional role of sulfenyl amide formation in the redox-regulated enzyme PTP1B,” Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 2, pp. 444–447, 2010.
[22]
U. Jakob, M. Eser, and J. C. A. Bardwell, “Redox switch of Hsp33 has a novel zinc-binding motif,” Journal of Biological Chemistry, vol. 275, no. 49, pp. 38302–38310, 2000.
[23]
J. Vijayalakshmi, M. K. Mukhergee, J. Graumann, U. Jakob, and M. A. Saper, “The 2.2 ? crystal structure of Hsp33: a heat shock protein with redox-regulated chaperone activity,” Structure, vol. 9, no. 5, pp. 367–375, 2001.
[24]
J. Mascarenhas, H. Sanchez, S. Tadesse et al., “Bacillus subtilis SbcC protein plays an important role in DNA inter-strand cross-link repair,” BMC Molecular Biology, vol. 7, article 20, 2006.
[25]
C. L. Colbert, Q. Wu, P. J. A. Erbel, K. H. Gardner, and J. Deisenhofer, “Mechanism of substrate specificity in Bacillus subtilis ResA, a thioredoxin-like protein involved in cytochrome c maturation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 12, pp. 4410–4415, 2006.
[26]
A. Singh, D. K. Crossman, D. Mai et al., “Mycobacterium tuberculosis WhiB3 Maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage response,” PLoS Pathogens, vol. 5, no. 8, Article ID e1000545, 2009.
[27]
A. Singh, L. Guidry, K. V. Narasimhulu et al., “Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its [4Fe-4S] cluster and is essential for nutrient starvation survival,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 28, pp. 11562–11567, 2007.
[28]
M. S. B. Paget, J. G. Kang, J. H. Roe, and M. J. Buttner, “ , an RNA polymerase sigma factor that modulates expression of the thioredoxin system in response to oxidative stress in Streptomyces coelicolor A3(2),” EMBO Journal, vol. 17, no. 19, pp. 5776–5782, 1998.
[29]
J. G. Kang, M. S. B. Paget, Y. J. Seok et al., “RsrA, an anti-sigma factor regulated by redox change,” EMBO Journal, vol. 18, no. 15, pp. 4292–4298, 1999.
[30]
W. Li, A. R. Bottrill, M. J. Bibb, M. J. Buttner, M. S. B. Paget, and C. Kleanthous, “The role of zinc in the disulphide stress-regulated anti-sigma factor RsrA from Streptomyces coelicolor,” Journal of Molecular Biology, vol. 333, no. 2, pp. 461–472, 2003.
[31]
K. G. Thakur, T. Praveena, and B. Gopal, “Structural and biochemical bases for the redox sensitivity of Mycobacterium tuberculosis RslA,” Journal of Molecular Biology, vol. 397, no. 5, pp. 1199–1208, 2010.
[32]
J. F. Collet, J. C. D'Souza, U. Jakob, and J. C. A. Bardwell, “Thioredoxin 2, an oxidative stress-induced protein, contains a high affinity zinc binding site,” Journal of Biological Chemistry, vol. 278, no. 46, pp. 45325–45332, 2003.
[33]
A. Lewin, A. Crow, C. T. C. Hodson, L. Hederstedt, and N. E. Le Brun, “Effects of substitutions in the CXXC active-site motif of the extracytoplasmic thioredoxin ResA,” Biochemical Journal, vol. 414, no. 1, pp. 81–91, 2008.
[34]
K. Uchida, “Histidine and lysine as targets of oxidative modification,” Amino Acids, vol. 25, no. 3-4, pp. 249–257, 2003.
[35]
I. Brune, H. Werner, A. T. Hüser, J. Kalinowski, A. Pühler, and A. Tauch, “The DtxR protein acting as dual transcriptional regulator directs a global regulatory network involved in iron metabolism of Corynebacterium glutamicum,” BMC Genomics, vol. 7, article 21, 2006.
[36]
V. Duarte and J. M. Latour, “PerR vs OhrR: selective peroxide sensing in Bacillus subtilis,” Molecular BioSystems, vol. 6, no. 2, pp. 316–323, 2010.
[37]
A. F. Herbig and J. D. Helmann, “Roles of metal ions and hydrogen peroxide in modulating the interaction of the Bacillus subtilis PerR peroxide regulon repressor with operator DNA,” Molecular Microbiology, vol. 41, no. 4, pp. 849–859, 2001.
[38]
J. W. Lee and J. D. Helmann, “The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation,” Nature, vol. 440, no. 7082, pp. 363–367, 2006.
[39]
D. A. K. Traoré, A. E. Ghazouani, L. Jacquamet et al., “Structural and functional characterization of 2-oxo-histidine in oxidized PerR protein,” Nature Chemical Biology, vol. 5, no. 1, pp. 53–59, 2009.
[40]
D. Ortiz de Orué Lucana, T. Schaa, and H. Schrempf, “The novel extracellular Streptomyces reticuli haem-binding protein HbpS influences the production of the catalase-peroxidase CpeB,” Microbiology, vol. 150, no. 8, pp. 2575–2585, 2004.
[41]
D. Ortiz de Orué Lucana, P. Zou, M. Nierhaus, and H. Schrempf, “Identification of a novel two-component system SenS/SenR modulating the production of the catalase-peroxidase CpeB and the haem-binding protein HbpS in Streptomyces reticuli,” Microbiology, vol. 151, no. 11, pp. 3603–3614, 2005.
[42]
P. Zou, M. R. Groves, S. D. Viale-Bouroncle, and D. Ortiz de Orué Lucana, “Cristallization and preliminary characterization of a novel haem-binding protein of Streptomyces reticuli,” Acta Crystallographica F, vol. 64, pp. 386–390, 2008.
[43]
D. Ortiz de Orué Lucana, G. Bogel, P. Zou, and M. R. Groves, “The oligomeric assembly of the novel haem-degrading protein HbpS is essential for interaction with its cognate two-component sensor kinase,” Journal of Molecular Biology, vol. 386, no. 4, pp. 1108–1122, 2009.
[44]
J. E. Nettleship, J. Brown, M. R. Groves, and A. Geerlof, “Methods for protein characterization by mass spectrometry, thermal shift (ThermoFluor) assay, and multiangle or static light scattering,” Methods in Molecular Biology, vol. 426, pp. 299–318, 2008.
[45]
D. Ortiz de Orué Lucana, M. Roscher, A. Honigmann, and J. Schwarz, “Iron-mediated oxidation induces conformational changes within the redox-sensing protein HbpS,” Journal of Biological Chemistry, vol. 285, no. 36, pp. 28086–28096, 2010.
[46]
M. M. S. M. W?sten, L. F. F. Kox, S. Chamnongpol, F. C. Soncini, and E. A. Groisman, “A signal transduction system that responds to extracellular iron,” Cell, vol. 103, no. 1, pp. 113–125, 2000.
[47]
S. Severance, S. Chakraborty, and D. J. Kosman, “The Ftr1p iron permease in the yeast plasma membrane: orientation, topology and structure-function relationships,” Biochemical Journal, vol. 380, no. 2, pp. 487–496, 2004.
[48]
K. Nishino, F. F. Hsu, J. Turk, M. J. Cromie, M. M. S. M. W?sten, and E. A. Groisman, “Identification of the lipopolysaccharide modifications controlled by the Salmonella PmrA/PmrB system mediating resistance to Fe(III) and Al(III),” Molecular Microbiology, vol. 61, no. 3, pp. 645–654, 2006.
[49]
Y. Tang and J. R. Guest, “Direct evidence for mRNA binding and post-transcriptional regulation by Escherichia coli aconitases,” Microbiology, vol. 145, no. 11, pp. 3069–3079, 1999.
[50]
S. Varghese, Y. Tang, and J. A. Imlay, “Contrasting sensitivities of Escherichia coli aconitases A and B to oxidation and iron depletion,” Journal of Bacteriology, vol. 185, no. 1, pp. 221–230, 2003.
[51]
A. Atanassova and D. B. Zamble, “Escherichia coli HypA is a zinc metalloprotein with a weak affinity for nickel,” Journal of Bacteriology, vol. 187, no. 14, pp. 4689–4697, 2005.
[52]
L. Escolar, J. Pérez-Martín, and V. De Lorenzo, “Opening the iron box: transcriptional metalloregulation by the fur protein,” Journal of Bacteriology, vol. 181, no. 20, pp. 6223–6229, 1999.