期刊论文详细信息
BMC Microbiology
The ColRS signal transduction system responds to the excess of external zinc, iron, manganese, and cadmium
Rita Hõrak1  Heili Ilves1  Karl Mumm1  Kadi Ainsaar1 
[1] Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia
关键词: Pseudomonas putida;    Signal perception;    Histidine kinase;    Metal tolerance;    ColRS two-component system;   
Others  :  821401
DOI  :  10.1186/1471-2180-14-162
 received in 2014-02-14, accepted in 2014-06-17,  发布年份 2014
PDF
【 摘 要 】

Background

The ColRS two-component system has been shown to contribute to the membrane functionality and stress tolerance of Pseudomonas putida as well as to the virulence of Pseudomonas aeruginosa and plant pathogenic Xanthomonas species. However, the conditions activating the ColRS pathway and the signal(s) sensed by ColS have remained unknown. Here we aimed to analyze the role of the ColRS system in metal tolerance of P. putida and to test whether ColS can respond to metal excess.

Results

We show that the ColRS system is necessary for P. putida to tolerate the excess of iron and zinc, and that it also contributes to manganese and cadmium tolerance. Excess of iron, zinc, manganese or cadmium activates ColRS signaling and as a result modifies the expression of ColR-regulated genes. Our data suggest that the genes in the ColR regulon are functionally redundant, as several loci have to be deleted to observe a significant decrease in metal tolerance. Site-directed mutagenesis of ColS revealed that excess of iron and, surprisingly, also zinc are sensed by a conserved ExxE motif in ColS’s periplasmic domain. While ColS is able to sense different metals, it still discriminates between the two oxidation states of iron, specifically responding to ferric and not ferrous iron. We propose a signal perception model involving a dimeric ColS, where each monomer donates one ExxE motif for metal binding.

Conclusions

Several transition metals are essential for living organisms in certain amounts, but toxic in excess. We show that ColRS is a sensor system which detects and responds to the excess of physiologically important metals such as zinc, iron and manganese. Thus, the ColRS system is an important factor for metal homeostasis and tolerance in P. putida.

【 授权许可】

   
2014 Ainsaar et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140712073838171.pdf 1634KB PDF download
Figure 8. 76KB Image download
Figure 7. 62KB Image download
Figure 6. 63KB Image download
Figure 5. 49KB Image download
Figure 4. 76KB Image download
Figure 3. 61KB Image download
Figure 2. 47KB Image download
Figure 1. 64KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

【 参考文献 】
  • [1]Andreini C, Bertini I, Cavallaro G, Holliday GL, Thornton JM: Metal ions in biological catalysis: from enzyme databases to general principles. J Biol Inorg Chem 2008, 13(8):1205-1218.
  • [2]Touati D: Iron and oxidative stress in bacteria. Arch Biochem Biophys 2000, 373(1):1-6.
  • [3]Imlay JA: Iron-sulphur clusters and the problem with oxygen. Mol Microbiol 2006, 59(4):1073-1082.
  • [4]McDevitt CA, Ogunniyi AD, Valkov E, Lawrence MC, Kobe B, McEwan AG, Paton JC: A molecular mechanism for bacterial susceptibility to zinc. PLoS Pathog 2011, 7(11):e1002357.
  • [5]Outten CE, O’Halloran TV: Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis. Science 2001, 292(5526):2488-2492.
  • [6]Changela A, Chen K, Xue Y, Holschen J, Outten CE, O’Halloran TV, Mondragon A: Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR. Science 2003, 301(5638):1383-1387.
  • [7]Nies DH: Efflux-mediated heavy metal resistance in prokaryotes. FEMS Microbiol Rev 2003, 27(2–3):313-339.
  • [8]Brocklehurst KR, Hobman JL, Lawley B, Blank L, Marshall SJ, Brown NL, Morby AP: ZntR is a Zn(II)-responsive MerR-like transcriptional regulator of zntA in Escherichia coli. Mol Microbiol 1999, 31(3):893-902.
  • [9]Outten FW, Outten CE, Hale J, O’Halloran TV: Transcriptional activation of an Escherichia coli copper efflux regulon by the chromosomal MerR homologue, cueR. J Biol Chem 2000, 275(40):31024-31029.
  • [10]Blindauer CA, Harrison MD, Parkinson JA, Robinson AK, Cavet JS, Robinson NJ, Sadler PJ: A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity. Proc Natl Acad Sci U S A 2001, 98(17):9593-9598.
  • [11]Pulliainen AT, Kauko A, Haataja S, Papageorgiou AC, Finne J: Dps/Dpr ferritin-like protein: insights into the mechanism of iron incorporation and evidence for a central role in cellular iron homeostasis in Streptococcus suis. Mol Microbiol 2005, 57(4):1086-1100.
  • [12]Hantke K: Bacterial zinc uptake and regulators. Curr Opin Microbiol 2005, 8(2):196-202.
  • [13]Moore CM, Helmann JD: Metal ion homeostasis in Bacillus subtilis. Curr Opin Microbiol 2005, 8(2):188-195.
  • [14]Carpenter BM, Whitmire JM, Merrell DS: This is not your mother’s repressor: the complex role of fur in pathogenesis. Infect Immun 2009, 77(7):2590-2601.
  • [15]Horsburgh MJ, Ingham E, Foster SJ: In Staphylococcus aureus, Fur is an interactive regulator with PerR, contributes to virulence, and Is necessary for oxidative stress resistance through positive regulation of catalase and iron homeostasis. J Bacteriol 2001, 183(2):468-475.
  • [16]Wösten MM, Kox LF, Chamnongpol S, Soncini FC, Groisman EA: A signal transduction system that responds to extracellular iron. Cell 2000, 103(1):113-125.
  • [17]Gunn JS: The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more. Trends Microbiol 2008, 16(6):284-290.
  • [18]Nishino K, Hsu FF, Turk J, Cromie MJ, Wosten MM, Groisman EA: Identification of the lipopolysaccharide modifications controlled by the Salmonella PmrA/PmrB system mediating resistance to Fe(III) and Al(III). Mol Microbiol 2006, 61(3):645-654.
  • [19]Kato A, Chen HD, Latifi T, Groisman EA: Reciprocal control between a bacterium’s regulatory system and the modification status of its lipopolysaccharide. Mol Cell 2012, 47(6):897-908.
  • [20]Ogasawara H, Shinohara S, Yamamoto K, Ishihama A: Novel regulation targets of the metal-response BasS-BasR two-component system of Escherichia coli. Microbiology 2012, 158(Pt 6):1482-1492.
  • [21]Leonhartsberger S, Huber A, Lottspeich F, Bock A: The hydH/G Genes from Escherichia coli code for a zinc and lead responsive two-component regulatory system. J Mol Biol 2001, 307(1):93-105.
  • [22]Appia-Ayme C, Hall A, Patrick E, Rajadurai S, Clarke TA, Rowley G: ZraP is a periplasmic molecular chaperone and a repressor of the zinc-responsive two-component regulator ZraSR. Biochem J 2012, 442(1):85-93.
  • [23]Timmis KN: Pseudomonas putida: a cosmopolitan opportunist par excellence. Environ Microbiol 2002, 4(12):779-781.
  • [24]Strateva T, Yordanov D: Pseudomonas aeruginosa - a phenomenon of bacterial resistance. J Med Microbiol 2009, 58(Pt 9):1133-1148.
  • [25]Dos Santos VA, Heim S, Moore ER, Stratz M, Timmis KN: Insights into the genomic basis of niche specificity of Pseudomonas putida KT2440. Environ Microbiol 2004, 6(12):1264-1286.
  • [26]Perron K, Caille O, Rossier C, Van Delden C, Dumas JL, Kohler T: CzcR-CzcS, a two-component system involved in heavy metal and carbapenem resistance in Pseudomonas aeruginosa. J Biol Chem 2004, 279(10):8761-8768.
  • [27]Teitzel GM, Geddie A, De Long SK, Kirisits MJ, Whiteley M, Parsek MR: Survival and growth in the presence of elevated copper: transcriptional profiling of copper-stressed Pseudomonas aeruginosa. J Bacteriol 2006, 188(20):7242-7256.
  • [28]Caille O, Rossier C, Perron K: A copper-activated two-component system interacts with zinc and imipenem resistance in Pseudomonas aeruginosa. J Bacteriol 2007, 189(13):4561-4568.
  • [29]Zhang XX, Rainey PB: Regulation of copper homeostasis in Pseudomonas fluorescens SBW25. Environ Microbiol 2008, 10(12):3284-3294.
  • [30]Moskowitz SM, Ernst RK, Miller SI: PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A. J Bacteriol 2004, 186(2):575-579.
  • [31]Winsor GL, Van Rossum T, Lo R, Khaira B, Whiteside MD, Hancock RE, Brinkman FS: Pseudomonas Genome Database: facilitating user-friendly, comprehensive comparisons of microbial genomes. Nucleic Acids Res 2009, 37:D483-D488.
  • [32]Dekkers LC, Bloemendaal CJ, de Weger LA, Wijffelman CA, Spaink HP, Lugtenberg BJ: A two-component system plays an important role in the root-colonizing ability of Pseudomonas fluorescens strain WCS365. Mol Plant Microbe Interact 1998, 11(1):45-56.
  • [33]Garvis S, Munder A, Ball G, de Bentzmann S, Wiehlmann L, Ewbank JJ, Tümmler B, Filloux A: Caenorhabditis elegans semi-automated liquid screen reveals a specialized role for the chemotaxis gene cheB2 in Pseudomonas aeruginosa virulence. PLoS Pathog 2009, 5(8):e1000540.
  • [34]Yan Q, Wang N: The ColR/ColS two-component system plays multiple roles in the pathogenicity of the citrus canker pathogen Xanthomonas citri subsp. citri. J Bacteriol 2011, 193(7):1590-1599.
  • [35]Subramoni S, Pandey A, Vishnupriya MR, Patel HK, Sonti RV: The ColRS system of Xanthomonas oryzae pv. oryzae is required for virulence and growth in iron-limiting conditions. Mol Plant Pathol 2012, 13(7):690-703.
  • [36]Kivistik PA, Putrinš M, Püvi K, Ilves H, Kivisaar M, Hõrak R: The ColRS two-component system regulates membrane functions and protects Pseudomonas putida against phenol. J Bacteriol 2006, 188(23):8109-8117.
  • [37]Putrinš M, Ilves H, Lilje L, Kivisaar M, Hõrak R: The impact of ColRS two-component system and TtgABC efflux pump on phenol tolerance of Pseudomonas putida becomes evident only in growing bacteria. BMC Microbiol 2010, 10:110.
  • [38]Putrinš M, Ainelo A, Ilves H, Hõrak R: The ColRS system is essential for the hunger response of glucose-growing Pseudomonas putida. BMC Microbiol 2011, 11:170.
  • [39]Putrinš M, Ilves H, Kivisaar M, Hõrak R: ColRS two-component system prevents lysis of subpopulation of glucose-grown Pseudomonas putida. Environ Microbiol 2008, 10(10):2886-2893.
  • [40]Kivistik PA, Kivi R, Kivisaar M, Hõrak R: Identification of ColR binding consensus and prediction of regulon of ColRS two-component system. BMC Mol Biol 2009, 10:46.
  • [41]de Weert S, Dekkers LC, Bitter W, Tuinman S, Wijfjes AH, van Boxtel R, Lugtenberg BJ: The two-component colR/S system of Pseudomonas fluorescens WCS365 plays a role in rhizosphere competence through maintaining the structure and function of the outer membrane. FEMS Microbiol Ecol 2006, 58(2):205-213.
  • [42]Zhang SS, He YQ, Xu LM, Chen BW, Jiang BL, Liao J, Cao JR, Liu D, Huang YQ, Liang XX, Tang TJ, Lu GT, Tang JL: A putative colR(XC1049)-colS(XC1050) two-component signal transduction system in Xanthomonas campestris positively regulates hrpC and hrpE operons and is involved in virulence, the hypersensitive response and tolerance to various stresses. Res Microbiol 2008, 159(7-8):569-578.
  • [43]Hu N, Zhao B: Key genes involved in heavy-metal resistance in Pseudomonas putida CD2. FEMS Microbiol Lett 2007, 267(1):17-22.
  • [44]Hõrak R, Ilves H, Pruunsild P, Kuljus M, Kivisaar M: The ColR-ColS two-component signal transduction system is involved in regulation of Tn4652 transposition in Pseudomonas putida under starvation conditions. Mol Microbiol 2004, 54(3):795-807.
  • [45]Lee LJ, Barrett JA, Poole RK: Genome-wide transcriptional response of chemostat-cultured Escherichia coli to zinc. J Bacteriol 2005, 187(3):1124-1134.
  • [46]Kreamer NN, Wilks JC, Marlow JJ, Coleman ML, Newman DK: BqsR/BqsS constitute a two-component system that senses extracellular Fe(II) in Pseudomonas aeruginosa. J Bacteriol 2012, 194(5):1195-1204.
  • [47]Ma Z, Jacobsen FE, Giedroc DP: Coordination chemistry of bacterial metal transport and sensing. Chem Rev 2009, 109(10):4644-4681.
  • [48]Stearman R, Yuan DS, Yamaguchi-Iwai Y, Klausner RD, Dancis A: A permease-oxidase complex involved in high-affinity iron uptake in yeast. Science 1996, 271(5255):1552-1557.
  • [49]Wedderhoff I, Kursula I, Groves MR, Ortiz de Orue Lucana D: Iron binding at specific sites within the octameric HbpS protects Streptomycetes from iron-mediated oxidative stress. PLoS One 2013, 8(8):e71579.
  • [50]Baker KR, Postle K: Mutations in Escherichia coli ExbB transmembrane domains identify scaffolding and signal transduction functions and exclude participation in a proton pathway. J Bacteriol 2013, 195(12):2898-2911.
  • [51]Wen J, Chen X, Bowie JU: Exploring the allowed sequence space of a membrane protein. Nat Struct Biol 1996, 3(2):141-148.
  • [52]Steele KH, O’Connor LH, Burpo N, Kohler K, Johnston JW: Characterization of a ferrous iron-responsive two-component system in nontypeable Haemophilus influenzae. J Bacteriol 2012, 194(22):6162-6173.
  • [53]Aguirre JD, Culotta VC: Battles with iron: manganese in oxidative stress protection. J Biol Chem 2012, 287(17):13541-13548.
  • [54]Leedjärv A, Ivask A, Virta M: Interplay of different transporters in the mediation of divalent heavy metal resistance in Pseudomonas putida KT2440. J Bacteriol 2008, 190(8):2680-2689.
  • [55]Trent MS, Ribeiro AA, Lin S, Cotter RJ, Raetz CR: An inner membrane enzyme in Salmonella and Escherichia coli that transfers 4-amino-4-deoxy-L-arabinose to lipid A: induction on polymyxin-resistant mutants and role of a novel lipid-linked donor. J Biol Chem 2001, 276(46):43122-43131.
  • [56]Breazeale SD, Ribeiro AA, McClerren AL, Raetz CR: A formyltransferase required for polymyxin resistance in Escherichia coli and the modification of lipid A with 4-Amino-4-deoxy-L-arabinose. Identification and function oF UDP-4-deoxy-4-formamido-L-arabinose. J Biol Chem 2005, 280(14):14154-14167.
  • [57]Tamayo R, Choudhury B, Septer A, Merighi M, Carlson R, Gunn JS: Identification of cptA, a PmrA-regulated locus required for phosphoethanolamine modification of the Salmonella enterica serovar typhimurium lipopolysaccharide core. J Bacteriol 2005, 187(10):3391-3399.
  • [58]Gunn JS, Lim KB, Krueger J, Kim K, Guo L, Hackett M, Miller SI: PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance. Mol Microbiol 1998, 27(6):1171-1182.
  • [59]Wösten MM, Groisman EA: Molecular characterization of the PmrA regulon. J Biol Chem 1999, 274(38):27185-27190.
  • [60]Chamnongpol S, Dodson W, Cromie MJ, Harris ZL, Groisman EA: Fe(III)-mediated cellular toxicity. Mol Microbiol 2002, 45(3):711-719.
  • [61]Chen HD, Groisman EA: The biology of the PmrA/PmrB two-component system: the major regulator of lipopolysaccharide modifications. Annu Rev Microbiol 2013, 67:83-112.
  • [62]Laitaoja M, Valjakka J, Janis J: Zinc coordination spheres in protein structures. Inorg Chem 2013, 52(19):10983-10991.
  • [63]Gutu AD, Sgambati N, Strasbourger P, Brannon MK, Jacobs MA, Haugen E, Kaul RK, Johansen HK, Hoiby N, Moskowitz SM: Polymyxin resistance of Pseudomonas phoQ mutants is dependent on additional two-component regulatory systems. Antimicrob Agents Chemother 2013, 57(5):2204-2215.
  • [64]Bayley SA, Duggleby CJ, Worsey MJ, Williams PA, Hardy KG, Broda P: Two modes of loss of the Tol function from Pseudomonas putida mt-2. Mol Gen Genet 1977, 154(2):203-204.
  • [65]Regenhardt D, Heuer H, Heim S, Fernandez DU, Strömpl C, Moore ER, Timmis KN: Pedigree and taxonomic credentials of Pseudomonas putida strain KT2440. Environ Microbiol 2002, 4(12):912-915.
  • [66]Sharma RC, Schimke RT: Preparation of electrocompetent E. coli using salt-free growth medium. Biotechniques 1996, 20(1):42-44.
  • [67]Martinez-Garcia E, de Lorenzo V: Engineering multiple genomic deletions in Gram-negative bacteria: analysis of the multi-resistant antibiotic profile of Pseudomonas putida KT2440. Environ Microbiol 2011, 13(10):2702-2716.
  • [68]Miller JH: A short course in bacterial genetics: a laboratory manual and handbook for Echerichia coli and related bacteria. Cold Spring Harbour, NY: Cold Spring Harbour Laboratory Press; 1992.
  文献评价指标  
  下载次数:67次 浏览次数:41次