Abstract
Bacteroides are gram-negative anaerobes and one of the most abundant members the lower GI tract microflora where they play an important role in normal intestinal physiology. Disruption of this commensal relationship has a great impact on human health and disease. Bacteroides spp. are significant opportunistic pathogens causing infections when the mucosal barrier integrity is disrupted following predisposing conditions such as GI surgery, perforated or gangrenous appendicitis, perforated ulcer, diverticulitis, trauma and inflammatory bowel diseases. B. fragilis accounts for 60–90 % of all anaerobic infections despite being a minor component of the genus (<1 % of the flora). Clinical strains of B. fragilis are among the most aerotolerant anaerobes. When shifted from anaerobic to aerobic conditions B. fragilis responds to oxidative stress by inducing the expression of an extensive set of genes involved in protection against oxygen derived radicals and iron homeostasis. In Bacteroides, little is known about the metal/oxidative stress interactions and the mobilization of intra-cellular non-heme iron during the oxidative stress response has been largely overlooked. Here we present an overview of the work carried out to demonstrate that both oxygen-detoxifying enzymes and iron-storage proteins are essential for B. fragilis to survive an adverse oxygen-rich environment. Some species of Bacteroides have acquired multiple homologues of the iron storage and detoxifying ferritin-like proteins but some species contain none. The proteins found in Bacteroides are classical mammalian H-type non-heme ferritin (FtnA), non-specific DNA binding and starvation protein (Dps) and the newly characterized bacterial Dps-Like miniferritin protein. The full contribution of ferritin-like proteins to pathophysiology of commensal and opportunistic pathogen Bacteroides spp. still remains to be elucidated.
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References
Andrews SC (1998) Iron storage in bacteria. Adv Microbiol Physiol 40:281–351
Andrews SC (2010) The ferritin-like superfamily: evolution of the biological iron storeman from a rubrerythrin-like ancestor. Biochim Biophys Acta 1800:691–705
Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101:15718–15723
Bernalier A, Dore J, Durand M (1999) Biochemistry of fermentation. In: Gibson GR, Roberfroid MB (eds) Colonic microbiota, nutrition and health. Kluwer Academic, Dordrecht, pp 37–53
Bou-Abdallah F (2010) The iron redox and hydrolysis chemistry of the ferritins. Biochim Biophys Acta 1800:719–731
Brook I (1989) Pathogenicity of Bacteroides fragilis group. Ann Clin Lab Sci 19:360–376
Brook I, Frazier EH (2000) Aerobic and anaerobic microbiology in intra-abdominal infections associated with diverticulitis. J Med Microbiol 49:827–830
Calhoun LN, Kwon YM (2010) Structure, function and regulation of the DNA-binding protein Dps and its role in acid and oxidative stress resistance in Escherichia coli: a review. J Appl Microbiol 110:375–386
Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA (2005) Diversity of the human intestinal microbial flora. Science 308:1635–1638
Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791
Finegold SM, George WL (1989) Anaerobic infections in humans. Academic Press, San Diego
Gao JL, Lu Y, Browne G, Yap BC, Trewhella J, Hunter N, Nguyen KA (2012) The role of heme binding by DNA-protective protein from starved cells (Dps) in the tolerance of Porphyromonas gingivalis to heme toxicity. J Biol Chem 287:42243–42258
Gauss GH, Benas P, Wiedenheft B, Young M, Douglas T, Lawrence CM (2006) Structure of the DPS-like protein from Sulfolobus solfataricus reveals a bacterioferritin-like dimetal binding site within a DPS-like dodecameric assembly. Biochemistry 45:10815–10827
Gauss GH, Reott MA, Rocha ER, Young MJ, Douglas T, Smith CJ, Lawrence CM (2012) Characterization of the Bacteroides fragilis bfr gene product identifies a bacterial DPS-like protein and suggests evolutionary links in the ferritin superfamily. J Bacteriol 194:15–27
Gibson GR, Roberfroid MB (1999) Colonic microbiota, nutrition and health. Kluwer Academic, Dordrecht
Hooper LV, Midtvedt T, Gordon JI (2002) How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 22:283–307
Imlay JA (2002) How oxygen damages microbes: oxygen tolerance and obligate anaerobiosis. Adv Microb Physiol 46:111–153
Jones DT, Taylor WR, Thornton JM (1992) The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci 8:275–282
Lund EK, Wharf SG, Fairweather-Tait SJ, Johnson IT (1999) Oral ferrous sulfate supplements increase the free radical-generating capacity of feces from healthy volunteers. Am J Clin Nutr 69:250–255
Mazuski JE, Solomkin JS (2009) Intra-abdominal infections. Surg Clin N Am 89:421–437
McClean KL, Sheehan GJ, Harding GK (1994) Intraabdominal infection: a review. Clin Infect Dis 19:100–116
McDermott PF, McMurry LM, Podglajen I, Dzink-Fox JL, Schneiders T, Draper MP, Levy SB (2008) The marC gene of Escherichia coli is not involved in multiple antibiotic resistance. Antimicrob Agents Chemother 52:382–383
Meehan BM, Malamy MH (2012) Fumarate reductase is a major contributor to the generation of reactive oxygen species in the anaerobe Bacteroides fragilis. Microbiology 158:539–546
Neish AS (2009) Microbes in gastrointestinal health and disease. Gastroenterology 136:65–80
Neu J, Douglas-Escobar M, Lopez M (2007) Microbes and the developing gastrointestinal tract. Nutr Clin Pract 22:174–182
Park Y, Choi JY, Yong D, Lee K, Kim JM (2009) Clinical features and prognostic factors of anaerobic infections: a 7-year retrospective study. Korean J Intern Med 24:13–18
Reading NC, Kasper DL (2011) The starting lineup: key microbial players in intestinal immunity and homeostasis. Frontiers Microbiol 2:1–10
Rocha ER, Smith CJ (1998) Characterization of a peroxide-resistant mutant of the anaerobic bacterium Bacteroides fragilis. J Bacteriol 180:5906–5912
Rocha ER, Smith CJ (2004) Transcriptional regulation of the Bacteroides fragilis ferritin gene (ftnA) by redox stress. Microbiology 150:2125–2134
Rocha ER, Smith CJ (2010) Heme and iron metabolism in Bacteroides. In: Andrews SC, Cornelis Pierre (eds) Iron uptake and homeostasis in microorganisms, chapter 9. Caister Academic, Norwich, pp 155–165
Rocha ER, Selby T, Coleman JP, Smith CJ (1996) Oxidative stress response in an anaerobe, Bacteroides fragilis: a role for catalase in protection against hydrogen peroxide. J Bacteriol 178:6895–6903
Rocha ER, Owens G Jr, Smith CJ (2000) The redox-sensitive transcriptional activator OxyR regulates the peroxide response regulon in the obligate anaerobe Bacteroides fragilis. J Bacteriol 182:5059–5069
Rocha ER, Herren CD, Smalley DJ, Smith CJ (2003) The complex oxidative stress response of Bacteroides fragilis: the role of OxyR in control of gene expression. Anaerobe 9:165–173
Rocha ER, Tzianabos AO, Smith CJ (2007) Thioredoxin reductase is essential for thiol/disulfide redox control and oxidative stress survival of the anaerobe Bacteroides fragilis. J Bacteriol 189:8015–8023
Rolfe RD, Hentges DJ, Barrett JT, Campbell BJ (1977) Oxygen tolerance of human intestinal anaerobes. Am J Clin Nutr 30:1762–1769
Savage DC (1977) Microbial ecology of the gastrointestinal tract. Ann Rev Microbiol 31:107–133
Sekirov I, Russell SL, Antunes CM, Finlay BB (2010) Gut microbiota in health and disease. Physiol Rev 90:859–904
Smith CJ, Rocha ER, Paster BJ (2006) The medically important Bacteroides spp. health and disease. In: Dworkin M, Falkow S, Rosenberg E, Schleifer KH, Stackebrandt E (eds) The prokaryotes, vol. 7. Springer, New York, pp 381–427
Sund CJ, Rocha ER, Tzianabos AO, Wells WG, Gee JM, Reott MA, O’Rourke DP, Smith CJ (2008) The Bacteroides fragilis transcriptome response to oxygen and H2O2: the role of OxyR and its effect on survival and virulence. Mol Microbiol 67:129–142
Tally FP, Stewart PR, Sutter VL, Rosenblatt JE (1975) Oxygen tolerance of fresh clinical anaerobic bacteria. J Clin Microbiol 1:161–164
Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28(10):2731–2739
Tappenden KA, Deutsch AS (2007) The physiological relevance of the intestinal microbiota—contributions to human health. J Am Coll Nutr 26:676S–683S
Touati D (2000) Iron and oxidative stress in bacteria. Arch Biochem Biophys 373:1–6
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031
van Till JW, van Veen SQ, van Ruler O, Lamme B, Gouma DJ, Boermeester MA (2007) The innate immune response to secondary peritonitis. Shock 28:504–517
Welch DK, Reilly CA, Aust SD (2002) The role of cysteine residues in the oxidation of ferritin. Free Rad Biol Med 33:399–408
Wexler HM (2007) Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev 20:593–621
Zhao G, Ceci P, Ilari A, Giangiacomo L, Laue TM, Chiancone E, Chasteen ND (2002) Iron and hydrogen peroxide detoxification properties of DNA-binding protein from starved cells. A ferritin-like DNA-binding protein of Escherichia coli. J Biol Chem 277:27689–27696
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This study was supported in part by NIH/NIAID Grants AI079183 to ERR and AI40588 to CJS.
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Rocha, E.R., Smith, C.J. Ferritin-like family proteins in the anaerobe Bacteroides fragilis: when an oxygen storm is coming, take your iron to the shelter. Biometals 26, 577–591 (2013). https://doi.org/10.1007/s10534-013-9650-2
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DOI: https://doi.org/10.1007/s10534-013-9650-2