The Clostridium difficile Dlt pathway is controlled by the extracytoplasmic function sigma factor σv in response to lysozyme

Infection and Immunity

Volumn 84, Issue 6, 2016, Pages 1902-1916

  Woods, Emily C ^a   Nawrocki, Kathryn L ^a   Suárez, Jose M ^a   McBride, Shonna M ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALINE PHOSPHATASE; CATIONIC ANTIMICROBIAL PEPTIDE; COMPLEMENTARY DNA; LYSOZYME; POLYPEPTIDE ANTIBIOTIC AGENT; SIGMA FACTOR; UNCLASSIFIED DRUG; ALANINE; BACTERIAL PROTEIN; CARRIER PROTEIN; D-ALANYL CARRIER PROTEIN, BACTERIA; ISOPROTEIN; TEICHOIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BACTERIAL CELL WALL; BACTERIAL GENE; BACTERIAL GROWTH; BACTERIAL STRAIN; BACTERIAL VIRULENCE; BACTERIUM MUTANT; CELL STRUCTURE; CLOSTRIDIUM DIFFICILE INFECTION; CONTROLLED STUDY; DLT GENE; FEMALE; GENE AMPLIFICATION; GENE EXPRESSION; GENOTYPE; HAMSTER MODEL; NONHUMAN; NULL ALLELE; OPERON; PEPTOCLOSTRIDIUM DIFFICILE; PHASE CONTRAST MICROSCOPY; PLASMID; PRIORITY JOURNAL; PROMOTER REGION; RAPID AMPLIFICATION OF COMPLEMENTARY DNA END; SIGD GENE; SIGT GENE; SIGV GENE; SITE DIRECTED MUTAGENESIS; ANIMAL; CELL WALL; CRICETULUS; DISEASE MODEL; GENE EXPRESSION REGULATION; GENETICS; HOST PATHOGEN INTERACTION; IMMUNOLOGY; METABOLISM; MICROBIOLOGY; MUTATION; PATHOGENICITY; PSEUDOMEMBRANOUS COLITIS; SIGNAL TRANSDUCTION; STEREOISOMERISM; VIRULENCE;

ALANINE; ANIMALS; BACTERIAL PROTEINS; CARRIER PROTEINS; CELL WALL; CLOSTRIDIUM DIFFICILE; CRICETULUS; DISEASE MODELS, ANIMAL; ENTEROCOLITIS, PSEUDOMEMBRANOUS; FEMALE; GENE EXPRESSION REGULATION, BACTERIAL; HOST-PATHOGEN INTERACTIONS; MURAMIDASE; MUTATION; OPERON; PROMOTER REGIONS, GENETIC; PROTEIN ISOFORMS; SIGMA FACTOR; SIGNAL TRANSDUCTION; STEREOISOMERISM; TEICHOIC ACIDS; VIRULENCE;

EID: 84971519470     PISSN: 00199567     EISSN: 10985522     Source Type: Journal    
DOI: 10.1128/IAI.00207-16     Document Type: Article

References (75)

1. Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC. 2015. Burden of Clostridium difficile infection in the United States. N Engl J Med 372: 825-834. http://dx.doi.org/10.1056/NEJMoa1408913.
2. Eckmann L. 2005. Defence molecules in intestinal innate immunity against bacterial infections. Curr Opin Gastroenterol 21: 147-151. http://dx.doi.org/10.1097/01.mog.0000153311.97832.8c.
3. Wah J, Wellek A, Frankenberger M, Unterberger P, Welsch U, Bals R. 2006. Antimicrobial peptides are present in immune and host defense cells of the human respiratory and gastrointestinal tracts. Cell Tissue Res 324: 449-456. http://dx.doi.org/10.1007/s00441-005-0127-7.
4. Tollin M, Bergman P, Svenberg T, Jornvall H, Gudmundsson GH, Agerberth B. 2003. Antimicrobial peptides in the first line defence of human colon mucosa. Peptides 24: 523-530. http://dx.doi.org/10.1016/S0196-9781(03)00114-1.
5. Lakshminarayanan B, Guinane CM, O'Connor PM, Coakley M, Hill C, Stanton C, O'Toole PW, Ross RP. 2013. Isolation and characterization of bacteriocin-producing bacteria from the intestinal microbiota of elderly Irish subjects. J Appl Microbiol 114: 886-898. http://dx.doi.org/10.1111/jam.12085.
6. Drissi F, Buffet S, Raoult D, Merhej V. 2015. Common occurrence of antibacterial agents in human intestinal microbiota. Front Microbiol 6: 441. http://dx.doi.org/10.3389/fmicb.2015.00441.
7. Muller CA, Autenrieth IB, Peschel A. 2005. Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci 62: 1297-1307. http://dx.doi.org/10.1007/s00018-005-5034-2.
8. Dommett R, Zilbauer M, George JT, Bajaj-Elliott M. 2005. Innate immune defence in the human gastrointestinal tract. Mol Immunol 42: 903-912. http://dx.doi.org/10.1016/j.molimm.2004.12.004.
9. Mason DY, Taylor CR. 1975. The distribution of muramidase (lysozyme) in human tissues. J Clin Pathol 28: 124-132. http://dx.doi.org/10.1136/jcp.28.2.124.
10. Nizet V. 2006. Antimicrobial peptide resistance mechanisms of human bacterial pathogens. Curr Issues Mol Biol 8: 11-26.
11. Nawrocki KL, Crispell EK, McBride SM. 2014. Antimicrobial peptide resistance mechanisms of gram-positive bacteria. Antibiotics (Basel) 3: 461-492. http://dx.doi.org/10.3390/antibiotics3040461.
12. McBride SM, Sonenshein AL. 2011. The dlt operon confers resistance to cationic antimicrobial peptides in Clostridium difficile. Microbiology 157: 1457-1465. http://dx.doi.org/10.1099/mic.0.045997-0.
13. Neuhaus FC, Baddiley J. 2003. A continuum of anionic charge: structures and functions of D-alanyl-teichoic acids in gram-positive bacteria. Microbiol Mol Biol Rev 67: 686-723. http://dx.doi.org/10.1128/MMBR.67.4.686-723.2003.
14. Le Jeune A, Torelli R, Sanguinetti M, Giard JC, Hartke A, Auffray Y, Benachour A. 2010. The extracytoplasmic function sigma factor SigV plays a key role in the original model of lysozyme resistance and virulence of Enterococcus faecalis. PLoS One 5: e9658. http://dx.doi.org/10.1371/journal.pone.0009658.
15. Guariglia-Oropeza V, Helmann JD. 2011. Bacillus subtilis sigma(V) confers lysozyme resistance by activation of two cell wall modification pathways, peptidoglycan O-acetylation and D-alanylation of teichoic acids. J Bacteriol 193: 6223-6232. http://dx.doi.org/10.1128/JB.06023-11.
16. Antunes A, Camiade E, Monot M, Courtois E, Barbut F, Sernova NV, Rodionov DA, Martin-Verstraete I, Dupuy B. 2012. Global transcriptional control by glucose and carbon regulator CcpA in Clostridium diffi-cile. Nucleic Acids Res 40: 10701-10718. http://dx.doi.org/10.1093/nar/gks864.
17. Cao M, Helmann JD. 2004. The Bacillus subtilis extracytoplasmic-function X factor regulates modification of the cell envelope and resistance to cationic antimicrobial peptides. J Bacteriol 186: 1136-1146. http://dx.doi.org/10.1128/JB.186.4.1136-1146.2004.
18. Estacio W, Anna-Arriola SS, Adedipe M, Marquez-Magana LM. 1998. Dual promoters are responsible for transcription initiation of the fla/che operon in Bacillus subtilis. J Bacteriol 180: 3548-3555.
19. Perego M, Glaser P, Minutello A, Strauch MA, Leopold K, Fischer W. 1995. Incorporation of D-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification of genes and regulation. J Biol Chem 270: 15598-15606.
20. Helmann JD. 2002. The extracytoplasmic function (ECF) sigma factors. Adv Microb Physiol 46: 47-110. http://dx.doi.org/10.1016/S0065-2911(02)46002-X.
21. Ho TD, Williams KB, Chen Y, Helm RF, Popham DL, Ellermeier CD. 2014. Clostridium difficile extracytoplasmic function sigma factor sigmaV regulates lysozyme resistance and is necessary for pathogenesis in the hamster model of infection. Infect Immun 82: 2345-2355. http://dx.doi.org/10.1128/IAI.01483-13.
22. Hastie JL, Williams KB, Sepulveda C, Houtman JC, Forest KT, Eller-meier CD. 2014. Evidence of a bacterial receptor for lysozyme: binding of lysozyme to the anti-sigma factor RsiV controls activation of the ECF sigma factor sigmaV. PLoS Genet 10: e1004643. http://dx.doi.org/10.1371/journal.pgen.1004643.
23. Luria SE, Burrous JW. 1957. Hybridization between Escherichia coli and Shigella. J Bacteriol 74: 461-476.
24. Smith CJ, Markowitz SM, Macrina FL. 1981. Transferable tetracycline resistance in Clostridium difficile. Antimicrob Agents Chemother 19: 997-1003. http://dx.doi.org/10.1128/AAC.19.6.997.
25. Bouillaut L, McBride SM, Sorg JA. 2011. Genetic manipulation of Clos-tridium difficile. Curr Protoc Microbiol Chapter 9:Unit 9A.2. http://dx.doi.org/10.1002/9780471729259.mc09a02s20.
26. Edwards AN, Suarez JM, McBride SM. 2013. Culturing and maintaining Clostridium difficile in an anaerobic environment. J Vis Exp (79):e50787. http://dx.doi.org/10.3791/50787.
27. Sorg JA, Dineen SS. 2009. Laboratory maintenance of Clostridium diffi-cile. Curr Protoc Microbiol Chapter 9:Unit 9A.1. http://dx.doi.org/10.1002/9780471729259.mc09a01s12.
28. Heap JT, Pennington OJ, Cartman ST, Carter GP, Minton NP. 2007. The ClosTron: a universal gene knock-out system for the genus Clostrid-ium. J Microbiol Methods 70: 452-464. http://dx.doi.org/10.1016/j.mimet.2007.05.021.
29. Karberg M, Guo H, Zhong J, Coon R, Perutka J, Lambowitz AM. 2001. Group II introns as controllable gene targeting vectors for genetic manipulation of bacteria. Nat Biotechnol 19: 1162-1167. http://dx.doi.org/10.1038/nbt1201-1162.
30. Ho TD, Ellermeier CD. 2011. PrsW is required for colonization, resistance to antimicrobial peptides, and expression of extracytoplasmic function sigma factors in Clostridium difficile. Infect Immun 79: 3229-3238. http://dx.doi.org/10.1128/IAI.00019-11.
31. Edwards AN, Pascual RA, Childress KO, Nawrocki KL, Woods EC, McBride SM. 2015. An alkaline phosphatase reporter for use in Clostridium difficile. Anaerobe 32: 98-104. http://dx.doi.org/10.1016/j.anaerobe.2015.01.002.
32. Dineen SS, Villapakkam AC, Nordman JT, Sonenshein AL. 2007. Repression of Clostridium difficile toxin gene expression by CodY. Mol Microbiol 66: 206-219. http://dx.doi.org/10.1111/j.1365-2958.2007.05906.x.
33. Edwards AN, Nawrocki KL, McBride SM. 2014. Conserved oligopeptide permeases modulate sporulation initiation in Clostridium difficile. Infect Immun 82: 4276-4291. http://dx.doi.org/10.1128/IAI.02323-14.
34. Purcell EB, McKee RW, McBride SM, Waters CM, Tamayo R. 2012. Cyclic diguanylate inversely regulates motility and aggregation in Clostrid-ium difficile. J Bacteriol 194: 3307-3316. http://dx.doi.org/10.1128/JB.00100-12.
35. Putnam EE, Nock AM, Lawley TD, Shen A. 2013. SpoIVA and SipL are Clostridium difficile spore morphogenetic proteins. J Bacteriol 195:1214-1225. http://dx.doi.org/10.1128/JB.02181-12.
36. McBride SM, Sonenshein AL. 2011. Identification of a genetic locus responsible for antimicrobial peptide resistance in Clostridium difficile. Infect Immun 79: 167-176. http://dx.doi.org/10.1128/IAI.00731-10.
37. Dineen SS, McBride SM, Sonenshein AL. 2010. Integration of metabolism and virulence by Clostridium difficile CodY. J Bacteriol 192:5350-5362. http://dx.doi.org/10.1128/JB.00341-10.
38. Suarez JM, Edwards AN, McBride SM. 2013. The Clostridium difficile cpr locus is regulated by a noncontiguous two-component system in response to type A and B lantibiotics. J Bacteriol 195: 2621-2631. http://dx.doi.org/10.1128/JB.00166-13.
39. Hyyrylainen HL, Vitikainen M, Thwaite J, Wu H, Sarvas M, Harwood CR, Kontinen VP, Stephenson K. 2000. D-Alanine substitution of teichoic acids as a modulator of protein folding and stability at the cytoplasmic membrane/cell wall interface of Bacillus subtilis. J Biol Chem 275: 26696-26703.
40. Fisher N, Shetron-Rama L, Herring-Palmer A, Heffernan B, Bergman N, Hanna P. 2006. The dltABCD operon of Bacillus anthracis Sterne is required for virulence and resistance to peptide, enzymatic, and cellular mediators of innate immunity. J Bacteriol 188: 1301-1309. http://dx.doi.org/10.1128/JB.188.4.1301-1309.2006.
41. Bartlett JG, Onderdonk AB, Cisneros RL, Kasper DL. 1977. Clindamycin-associated colitis due to a toxin-producing species of Clostridium in hamsters. J Infect Dis 136: 701-705. http://dx.doi.org/10.1093/infdis/136.5.701.
42. Chang TW, Bartlett JG, Gorbach SL, Onderdonk AB. 1978. Clindamycin-induced enterocolitis in hamsters as a model of pseudomembranous colitis in patients. Infect Immun 20: 526-529.
43. Wilson KH, Silva J, Fekety FR. 1981. Suppression of Clostridium difficile by normal hamster cecal flora and prevention of antibiotic-associated cecitis. Infect Immun 34: 626-628.
44. George WL, Sutter VL, Citron D, Finegold SM. 1979. Selective and differential medium for isolation of Clostridium difficile. J Clin Microbiol 9: 214-219.
45. Bordeleau E, Purcell EB, Lafontaine DA, Fortier LC, Tamayo R, Burrus V. 2015. Cyclic di-GMP riboswitch-regulated type IV pili contribute to aggregation of Clostridium difficile. J Bacteriol 197: 819-832. http://dx.doi.org/10.1128/JB.02340-14.
46. McKee RW, Mangalea MR, Purcell EB, Borchardt EK, Tamayo R. 2013. The second messenger cyclic di-GMP regulates Clostridium difficile toxin production by controlling expression of sigD. J Bacteriol 195: 5174-5185. http://dx.doi.org/10.1128/JB.00501-13.
47. Lyras D, O'Connor JR, Howarth PM, Sambol SP, Carter GP, Phumoonna T, Poon R, Adams V, Vedantam G, Johnson S, Gerding DN, Rood JI. 2009. Toxin B is essential for virulence of Clostridium difficile. Nature 458: 1176-1179. http://dx.doi.org/10.1038/nature07822.
48. Kuehne SA, Cartman ST, Heap JT, Kelly ML, Cockayne A, Minton NP. 2010. The role of toxin A and toxin B in Clostridium difficile infection. Nature 467: 711-713. http://dx.doi.org/10.1038/nature09397.
49. Goulding D, Thompson H, Emerson J, Fairweather NF, Dougan G, Douce GR. 2009. Distinctive profiles of infection and pathology in hamsters infected with Clostridium difficile strains 630 and B1. Infect Immun 77: 5478-5485. http://dx.doi.org/10.1128/IAI.00551-09.
50. Viswanathan VK. 2014. Memories of a virulent past. Gut Microbes 5: 143-145. http://dx.doi.org/10.4161/gmic.28340.
51. Wu X, Hurdle JG. 2014. The Clostridium difficile proline racemase is not essential for early logarithmic growth and infection. Can J Microbiol 60: 251-254. http://dx.doi.org/10.1139/cjm-2013-0903.
52. Hancock RE, Diamond G. 2000. The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol 8: 402-410. http://dx.doi.org/10.1016/S0966-842X(00)01823-0.
53. Peschel A. 2002. How do bacteria resist human antimicrobial peptides? Trends Microbiol 10:179-186. http://dx.doi.org/10.1016/S0966-842X(02)02333-8.
54. Kelly CP, Becker S, Linevsky JK, Joshi MA, O'Keane JC, Dickey BF, LaMont JT, Pothoulakis C. 1994. Neutrophil recruitment in Clostridium difficile toxin A enteritis in the rabbit. J Clin Invest 93: 1257-1265. http://dx.doi.org/10.1172/JCI117080.
55. Kelly CP, Kyne L. 2011. The host immune response to Clostridium diffi-cile. J Med Microbiol 60: 1070-1079. http://dx.doi.org/10.1099/jmm.0.030015-0.
56. Redelings MD, Sorvillo F, Mascola L. 2007. Increase in Clostridium difficile-related mortality rates, United States, 1999-2004. Emerg Infect Dis 13: 1417-1419. http://dx.doi.org/10.3201/eid1309.061116.
57. McDonald LC, Killgore GE, Thompson A, Owens RC, Jr, Kazakova SV, Sambol SP, Johnson S, Gerding DN. 2005. An epidemic, toxin genevariant strain of Clostridium difficile. N Engl J Med 353: 2433-2441. http://dx.doi.org/10.1056/NEJMoa051590.
58. Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J, Frost E, McDonald LC. 2005. Toxin production by an emerging strain of Clostrid-ium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 366: 1079-1084. http://dx.doi.org/10.1016/S0140-6736(05)67420-X.
59. Sebaihia M, Wren BW, Mullany P, Fairweather NF, Minton N, Stabler R, Thomson NR, Roberts AP, Cerdeno-Tarraga AM, Wang H, Holden MT, Wright A, Churcher C, Quail MA, Baker S, Bason N, Brooks K, Chillingworth T, Cronin A, Davis P, Dowd L, Fraser A, Feltwell T, Hance Z, Holroyd S, Jagels K, Moule S, Mungall K, Price C, Rabbinowitsch E, Sharp S, Simmonds M, Stevens K, Unwin L, Whithead S, Dupuy B, Dougan G, Barrell B, Parkhill J. 2006. The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nat Genet 38: 779-786. http://dx.doi.org/10.1038/ng1830.
60. Opitz B, Schroder NW, Spreitzer I, Michelsen KS, Kirschning CJ, Hallatschek W, Zahringer U, Hartung T, Gobel UB, Schumann RR. 2001. Toll-like receptor-2 mediates Treponema glycolipid and lipoteichoic acid-induced NF-kappaB translocation. J Biol Chem 276: 22041-22047. http://dx.doi.org/10.1074/jbc.M010481200.
61. Schroder NW, Morath S, Alexander C, Hamann L, Hartung T, Zahringer U, Gobel UB, Weber JR, Schumann RR. 2003. Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus au-reus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J Biol Chem 278: 15587-15594. http://dx.doi.org/10.1074/jbc.M212829200.
62. Cox KH, Ruiz-Bustos E, Courtney HS, Dale JB, Pence MA, Nizet V, Aziz RK, Gerling I, Price SM, Hasty DL. 2009. Inactivation of DltA modulates virulence factor expression in Streptococcus pyogenes. PLoS One 4: e5366. http://dx.doi.org/10.1371/journal.pone.0005366.
63. Morath S, Geyer A, Hartung T. 2001. Structure-function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus. J Exp Med 193: 393-398. http://dx.doi.org/10.1084/jem.193.3.393.
64. Grangette C, Nutten S, Palumbo E, Morath S, Hermann C, Dewulf J, Pot B, Hartung T, Hols P, Mercenier A. 2005. Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant synthesizing modified teichoic acids. Proc Natl Acad Sci U S A 102: 10321-10326. http://dx.doi.org/10.1073/pnas.0504084102.
65. Tabuchi Y, Shiratsuchi A, Kurokawa K, Gong JH, Sekimizu K, Lee BL, Nakanishi Y. 2010. Inhibitory role for D-alanylation of wall teichoic acid in activation of insect Toll pathway by peptidoglycan of Staphylococcusaureus. J Immunol 185: 2424-2431. http://dx.doi.org/10.4049/jimmunol.1000625.
66. Savidge TC, Pan WH, Newman P, O'Brien M, Anton PM, Pothoulakis C. 2003. Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine. Gastroenterology 125: 413-420. http://dx.doi.org/10.1016/S0016-5085(03)00902-8.
67. Kim H, Rhee SH, Kokkotou E, Na X, Savidge T, Moyer MP, Pothoulakis C, LaMont JT. 2005. Clostridium difficile toxin A regulates inducible cyclooxygenase-2 and prostaglandin E2 synthesis in colonocytes via reac-tive oxygen species and activation of p38 MAPK. J Biol Chem 280: 21237-21245. http://dx.doi.org/10.1074/jbc.M413842200.
68. Stevenson E, Minton NP, Kuehne SA. 2015. The role of flagella in Clostridium difficile pathogenicity. Trends Microbiol 23: 275-282. http://dx.doi.org/10.1016/j.tim.2015.01.004.
69. Wust J, Hardegger U. 1983. Transferable resistance to clindamycin, erythromycin, and tetracycline in Clostridium difficile. Antimicrob Agents Chemother 23: 784-786. http://dx.doi.org/10.1128/AAC.23.5.784.
70. Hussain HA, Roberts AP, Mullany P. 2005. Generation of an erythromycin-sensitive derivative of Clostridium difficile strain 630 (630Deltaerm) and demonstration that the conjugative transposon Tn916DeltaE enters the genome of this strain at multiple sites. J Med Microbiol 54: 137-141. http://dx.doi.org/10.1099/jmm.0.45790-0.
71. O'Connor JR, Lyras D, Farrow KA, Adams V, Powell DR, Hinds J, Cheung JK, Rood JI. 2006. Construction and analysis of chromosomal Clostridium difficile mutants. Mol Microbiol 61: 1335-1351. http://dx.doi.org/10.1111/j.1365-2958.2006.05315.x.
72. Stabler RA, He M, Dawson L, Martin M, Valiente E, Corton C, Lawley TD, Sebaihia M, Quail MA, Rose G, Gerding DN, Gibert M, Popoff MR, Parkhill J, Dougan G, Wren BW. 2009. Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium. Genome Biol 10: R102. http://dx.doi.org/10.1186/gb-2009-10-9-r102.
73. Thomas CM, Smith CA. 1987. Incompatibility group P plasmids: genetics, evolution, and use in genetic manipulation. Annu Rev Microbiol 41: 77-101. http://dx.doi.org/10.1146/annurev.mi.41.100187.000453.
74. Yanisch-Perron C, Vieira J, Messing J. 1985. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene 33: 103-119. http://dx.doi.org/10.1016/0378-1119(85)90120-9.
75. Manganelli R, Provvedi R, Berneri C, Oggioni MR, Pozzi G. 1998. Insertion vectors for construction of recombinant conjugative transposons in Bacillus subtilis and Enterococcus faecalis. FEMS Microbiol Lett 168: 259-268. http://dx.doi.org/10.1111/j.1574-6968.1998.tb13282.x.