Source: http://www.asmscience.org/content/book/10.1128/9781555817107.ch08
Timestamp: 2019-04-21 00:24:27+00:00

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Aggregatibacter actinomycetemcomitans is a small, gram-negative, facultatively anaerobic coccobacillus that belongs in the family Pasteurellaceae. A localized form of the disease, localized aggressive periodontitis, was originally found to be associated with the presence of A. actinomycetemcomitans in periodontal pockets. Genetic analyses show that the JP2 clone constitutes a subpopulation of restriction fragment length polymorphism (RFLP) group II. All isolates of the JP2 clone are serotype b, are identical in multilocus enzyme electrophoresis, and have the same DNA fingerprint using the restriction enzyme MspI, but show variation in ribotype. The RFLP group II strains, including strain JP2, have elevated expression of cytolethal distending toxin (CDT) measured as cytotoxicity for Chinese hamster ovary cells. Genomic islands that carry the leukotoxin gene cluster, the lipooligosaccharide biosynthesis gene cluster, the tight adherence gene cluster, and the CDT gene cluster are common to HK1651, D11S-1, and D7S-1 strains, whereas the other islands are strain specific. Members of the author&apos;s group used multilocus sequence analysis to study microevolution of the JP2 clone. Based on the assumptions that the variations were caused by single-site mutations and that each mutation occurred only once, it was possible to deduce an evolutionary model for A. actinomycetemcomitans serotype b, including the origin of the JP2 clone.
Map of the leukotoxin (ltx) operon in A. actinomycetemcomitans. The genes in the ltx operon are labeled A to D where ltxA is the structural gene, the gene product of ltxC is required for activation of the toxin, and ltxB and ltxD encode proteins that assist in secretion of the toxin. The 530-bp deletion in the promoter region in strains of the JP2 clone is indicated by dashed lines, and the insertion sequence found in a Japanese strain is denoted IS.
Phylogenetic tree constructed on the basis of substitutions in the partial genome sequences. The core segments, shared by all strains, of a Mauve alignment of the four A. actinomycetemcomitans were used for tree construction.
DNA asymmetry and DnaA box distribution on the chromosome of A. actinomycetemcomitans strain HK1651. Chromosome coordinates are shown on the x axis beginning with the dnaA gene as in the databases. The gray line and the right y axis show the (G-C) DNA asymmetry. Black vertical lines with diamonds and the left y axis show the DnaA box distribution and a peak indicates presence of a cluster of three close DnaA boxes as described previously ( 52 ). The figure was kindly provided by P. Mackiewicz.
1. Baehni, P. C.,, C.-C. Tsai,, W. P. McArthur,, B. F. Hammond,, B. J. Shenker, and, N. S. Taichman. 1981. Leukotoxic activity in different strains of the bacterium Actinobacillus actinomycetemcomitans isolated from juvenile periodontitis in man. Arch. Oral Biol. 26: 671– 676.
2. Balashova, N. V.,, J. A. Crosby,, L. Al Ghofaily, and, S. C. Kachlany. 2006. Leukotoxin confers beta-hemolytic activity to Actinobacillus actinomycetemcomitans. Infect. Immun. 74: 2015– 2021.
3. Balashova, N. V.,, C. Shah,, J. K. Patel,, S. Megalla, and, S. C. Kachlany. 2009. Actinobacillus actinomycetemcomitans LtxC is required for leukotoxin activity and initial interaction between toxin and host cells. Gene 443: 42– 47.
4. Bentley, S. D.,, and J. Parkhill. 2004. Comparative genomic structure of prokaryotes. Annu. Rev. Genet. 38: 771– 791.
5. Brogan, J. M.,, E. T. Lally,, K. Poulsen,, M. Kilian, and, D. R. Demuth. 1994. Regulation of Actinobacillus actinomycetemcomitans leukotoxin expression: analysis of the promoter regions of leukotoxic and minimally leukotoxic strains. Infect. Immun. 62: 501– 508.
6. Bueno, L. C.,, M. P. Mayer, and, J. M. DiRienzo. 1998. Relationship between conversion of localized juvenile periodontitis-susceptible children from health to disease and Actinobacillus actinomycetemcomitans leukotoxin promoter structure. J. Periodontol. 69: 998– 1007.
7. Chen, C.,, W. Kittichotirat,, W. Chen,, J. S. Downey,, Y. Si, and, R. Bumgarner. 2010. Genome sequence of naturally competent Aggregatibacter actinomycetemcomitans serotype a strain D7S-1. J. Bacteriol. 192: 2643– 2644.
8. Chen, C.,, W. Kittichotirat,, Y. Si, and, R. Bumgarner. 2009. Genome sequence of Aggregatibacter actinomycetemcomitans serotype c strain D11S-1. J. Bacteriol. 191: 7378– 7379.
9. Chen, J.,, D. J. Leblanc, and, D. M. Galli. 2002. DNA inversion on conjugative plasmid pVT745. J. Bacteriol. 184: 5926– 5934.
10. Chen, W.,, Y. Wang, and, C. Chen. 2005. Identification of a genomic island of Actinobacillus actinomycetemcomitans. J. Periodontol. 76: 2053– 2060.
11. Contreras, A.,, T. Rusitanonta,, C. Chen,, W. G. Wagner,, B. S. Michalowicz, and, J. Slots. 2000. Frequency of 530-bp deletion in Actinobacillus actinomycetemcomitans leukotoxin promoter region. Oral Microbiol. Immunol. 15: 338– 340.
12. Cortelli, J. R.,, S. C. Cortelli,, S. Jordan,, V. I. Haraszthy, and, J. J. Zambon. 2005. Prevalence of periodontal pathogens in Brazilians with aggressive or chronic periodontitis. J. Clin. Periodontol. 32: 860– 866.
13. Cortelli, S. C.,, F. O. Costa,, T. Kawai,, D. R. Aquino,, G. C. N. Franco,, K. Ohara,, C. V. G. Roman-Torres, and, J. R. Cortelli. 2009. Diminished treatment response of periodontally diseased patients infected with the JP2 clone of Aggregatibacter ( Actinobacillus) actinomycetemcomitans. J. Clin. Microbiol. 47: 2018– 2025.
14. DiBonaventura, M. P.,, R. DeSalle,, M. Pop,, N. Nagarajan,, D. H. Figurski,, D. H. Fine,, J. B. Kaplan, and, P. J. Planet. 2009. Complete genome sequence of Aggregatibacter ( Haemophilus) aphrophilus NJ8700. J. Bacteriol. 191: 4693– 4694.
15. DiRienzo, J. M.,, J. Slots,, M. Sixou,, M. A. Sol,, R. Harmon, and, T. L. McKay. 1994. Specific genetic variants of Actinobacillus actinomycetemcomitans correlate with disease and health in a regional population of families with localized juvenile periodontitis. Infect. Immun. 62: 3058– 3065.
16. DiRienzo, J. M.,, and T. L. McKay. 1994. Identification and characterization of genetic cluster groups of Actinobacillus actinomycetemcomitans isolated from the human oral cavity. J. Clin. Microbiol. 32: 75– 81.
17. Doungudomdacha, S.,, A Volgina, and, J. M. DiRienzo. 2007. Evidence that the cytolethal distending toxin locus was once part of a genomic island in the periodontal pathogen Aggregatibacter ( Actinobacillus) actinomycetemcomitans strain Y4. J. Med. Microbiol. 56: 1519– 1527.
18. Eisen, J. A.,, J. F. Heidelberg,, O. White, and, S. L. Salzberg. 2000. Evidence for symmetric chromosomal inversions around the replication origin in bacteria. Genome Biol. 1: 0011.1– 0011. 9.
19. Eriksen, K. T.,, D. Haubek, and, K. Poulsen. 2005. Intragenomic recombination in the highly leukotoxic JP2 clone of Actinobacillus actinomycetemcomitans. Microbiology 151: 3371– 3379.
20. Fabris, A. S.,, J. M. DiRienzo,, M. Wikstrom, and, M. P. Mayer. 2002. Detection of cytolethal distending toxin activity and cdt genes in Actinobacillus actinomycetemcomitans isolates from geographically diverse populations. Oral Microbiol. Immunol. 17: 231– 238.
21. Faveri, M.,, M. P. A. Mayer,, M. Feres,, L. C. de Figueiredo,, F. E. Dewhirst, and, B. J. Paster. 2008. Microbiological diversity of generalized aggressive periodontitis by 16S rRNA clonal analysis. Oral Microbiol. Immunol. 23: 112– 118.
22. Galli, D. M.,, J. Chen,, K. F. Novak, and, D. J. Leblanc. 2001. Nucleotide sequence and analysis of conjugative plasmid pVT745. J. Bacteriol. 183: 1585– 1594.
23. Guthmiller, J. M.,, E. T. Lally, and, J. Korostoff. 2001. Beyond the specific plaque hypothesis: are highly leukotoxic strains of Actinobacillus actinomycetemcomitans a paradigm for periodontal pathogenesis? Crit. Rev. Oral Biol. Med. 12: 116– 124.
24. Haraszthy, V. I.,, G. Hariharan,, E. M. B. Tinoco,, J. R. Cortelli,, E. T. Lally,, E. Davis, and, J. J. Zambon. 2000. Evidence for the role of highly leukotoxic Actinobacillus actinomycetemcomitans in the pathogenesis of localized juvenile and other forms of early-onset periodontitis. J. Periodontol. 71: 912– 922.
25. Haubek, D.,, J. M. DiRienzo,, E. M. Tinoco,, J. Westergaard,, N. J. Lopez,, C. P. Chung,, K. Poulsen, and, M. Kilian. 1997. Racial tropism of a highly toxic clone of Actinobacillus actinomycetemcomitans associated with juvenile periodontitis. J. Clin. Microbiol. 35: 3037– 3042.
26. Haubek, D.,, O.-K. Ennibi,, K. Poulsen,, N. Benzarti, and, V. Baelum. 2004. The highly leukotoxic JP2 clone of Actinobacillus actinomycetemcomitans and progression of periodontal attachment loss. J. Dent. Res. 83: 767– 770.
27. Haubek, D.,, O.-K. Ennibi,, K. Poulsen,, S. Poulsen,, N. Benzarti, and, M. Kilian. 2001. Early-onset periodontitis in Morocco is associated with the highly leukotoxic clone of Actinobacillus actinomycetemcomitans. J. Dent. Res. 80: 1580– 1583.
28. Haubek, D.,, O.-K. Ennibi,, K. Poulsen,, M. Væth,, S. Poulsen, and, M. Kilian. 2008. Risk of aggressive periodontitis in adolescent carriers of the JP2 clone of Aggregatibacter ( Actinobacillus) actinomycetemcomitans in Morocco: a prospective longitudinal cohort study. Lancet 371: 237– 242.
29. Haubek, D.,, A. Havemose-Poulsen, and, J. Westergaard. 2006. Aggressive periodontitis in a 16-year-old Ghanaian adolescent, the original source of Actinobacillus actinomycetemcomitans strain HK1651—a 10-year follow up. Int. J. Paediatr. Dent. 16: 370– 375.
30. Haubek, D.,, K. Poulsen,, S. Asikainen, and, M. Kilian. 1995. Evidence for absence in Northern Europe of especially virulent clonal types of Actinobacillus actinomycetemcomitans. J. Clin. Microbiol. 33: 395– 401.
31. Haubek, D.,, K. Poulsen, and, M. Kilian. 2007. Microevolution and patterns of dissemination of the JP2 clone of Aggregatibacter ( Actinobacillus) actinomycetemcomitans. Infect. Immun. 75: 3080– 3088.
32. Haubek, D.,, K. Poulsen,, J. Westergaard,, G. Dahlen, and, M. Kilian. 1996. Highly toxic clone of Actinobacillus actinomycetemcomitans in geographically widespread cases of juvenile periodontitis in adolescents of African origin. J. Clin. Microbiol. 34: 1576– 1578.
33. Haubek, D.,, K. Willi,, K. Poulsen,, J. Meyer, and, M. Kilian. 1997. Presence of bacteriophage Aa phi 23 correlates with the population genetic structure of Actinobacillus actinomycetemcomitans. Eur. J. Oral Sci. 105: 2– 8.
34. Hayashida, H.,, K. Poulsen, and, M. Kilian. 2002. Differences in iron acquisition from human haemoglobin among strains of Actinobacillus actinomycetemcomitans. Microbiology 148: 3993– 4001.
35. Hayashida, H.,, K. Poulsen,, O. Takagi, and, M. Kilian. 2000. Phylogenetic associations of IS Aa1 and IS 150-like insertion sequences in Actinobacillus actinomycetemcomitans. Microbiology 146: 1977– 1985.
36. He, T.,, T. Nishihara,, D. R. Demuth, and, I. Ishikawa. 1999. A novel insertion sequence increases the expression of leukotoxicity in Actinobacillus actinomycetemcomitans clinical isolates. J. Periodontol. 70: 1261– 1268.
37. Holm, P. 1950. Studies on the etiology of human actinomycosis. I. The “other microbes” and their importance. Acta Pathol. Scand. 27: 736– 751.
38. Hughes, D. 2000. Evaluating genome dynamics: the constraints on rearrangements within bacterial genomes. Genome Biol. 1: 0006.1– 0006.8.
39. Kaplan, J. B.,, M. B. Perry,, L. L. MacLean. D. Furgang,, M. E. Wilson, and, D. H. Fine. 2001. Structural and genetic analyses of O polysaccharide from Actinobacillus actinomycetemcomitans serotype f. Infect. Immun. 69: 5375– 5384.
40. Kaplan, J. B.,, H. C. Schreiner,, D. Furgang, and, D. H. Fine. 2002. Population structure and genetic diversity of Actinobacillus actinomycetemcomitans strains isolated from localized juvenile periodontitis patients. J. Clin. Microbiol. 40: 1181– 1187.
41. Kilian, M.,, E. V. Frandsen,, D. Haubek, and, K. Poulsen. 2006. The etiology of periodontal disease revisited by population genetic analysis. Periodontol. 2000 42: 158– 179.
42. Kilian, M.,, and C. R. Schiøtt. 1975. Haemophili and related bacteria in the human oral cavity. Arch. Oral Biol. 20: 791– 796.
43. Kittichotirat, W.,, R. Bumgarner, and, C. Chen. 2010. Markedly different genome arrangements between serotype a strains and serotype b or c strains of Aggregatibacter actinomycetemcomitans. BMC Genomics 11: 489.
44. Kolodrubetz, D.,, T. Dailey,, J. Ebersole, and, E. Kraig. 1989. Cloning and expression of the leukotoxin gene from Actinobacillus actinomycetemcomitans. Infect. Immun. 57: 1465– 1469.
45. Kraig, E.,, T. Dailey, and, D. Kolodrubetz. 1990. Nucleotide sequence of the leukotoxin gene from Actinobacillus actinomycetemcomitans: homology to the alphahemolysin/leukotoxin gene family. Infect. Immun. 58: 920– 929.
46. Krawiec, S.,, and M. Riley. 1990. Organization of the bacterial chromosome. Microbiol. Rev. 54: 502– 539.
47. Lakio, L.,, S. Paju,, G. Alfthan,, T. Tiirola,, S. Asikainen, and, P. J. Pussinen. 2003. Actinobacillus actinomycetemcomitans serotype d-specific antigen contains the O antigen of lipopolysaccharide. Infect. Immun. 71: 5005– 5011.
48. Lally, E. T.,, E. E. Golub,, I. R. Kieba,, N. S. Taichman,, J. Rosenbloom,, J. C. Rosen-bloom,, C. W. Gibson, and, D. R. Demuth. 1989. Analysis of the Actinobacillus actinomycetemcomitans leukotoxin gene. J. Biol. Chem. 264: 15451– 15456.
49. LeBlanc, D. J.,, L. N. Lee,, A. R. Abu-Al-Jaibat,, P. K. Sreenivasan, and, P. M. Fives-Taylor. 1993. Identification of plasmids in Actinobacillus actinomycetemcomitans and construction of intergeneric shuttle plasmids. Oral Microbiol. Immunol. 8: 94– 99.
50. Lepine, G.,, S. Caudry,, J. M. DiRienzo, and, R. P. Ellen. 1998. Epithelial cell invasion by Actinobacillus actinomycetemcomitans strains from restriction fragment-length polymorphism groups associated with juvenile periodontitis or carrier status. Oral Microbiol. Immunol. 13: 341– 347.
51. Liu, S.-L.,, and K. E. Sanderson. 1996. Highly plastic chromosomal organization in Salmonella typhi. Proc. Natl. Acad. Sci. USA 93: 10303– 10308.
52. Mackiewicz, P.,, J. Zakrzewska-Czerwinska,, A. Zawilak,, M. R. Dudek, and, S. Cebrat. 2004. Where does bacterial replication start? Rules for predicting the oriC region. Nucleic Acids Res. 32: 3781– 3791.
53. Mayer, M. P.,, L. C. Bueno,, E. J. Hansen, and, J. M. DiRienzo. 1999. Identification of a cytolethal distending toxin gene locus and features of a virulence-associated region in Actinobacillus actinomycetemcomitans. Infect. Immun. 67: 1227– 1237.
54. Maynard-Smith, J. 1995. Do bacteria have population genetics, p. 1–13. In S. Baumberg,, J. P. W. Young,, E. M. H. Wellington, and, J. R. Saunders (ed.) Population Genetics of Bacteria. Cambridge University Press, Cambridge, United Kingdom.
55. Narayanan, S. K.,, T. G. Nagaraja,, M. M. Chengappa, and, G. C. Stewart. 2002. Leukotoxins of gram-negative bacteria. Vet. Microbiol. 84: 337– 356.
56. Nørskov-Lauritsen, N.,, and M. Kilian. 2006. Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomycetemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb. nov. and Aggregatibacter segnis comb. nov., and emended description of Aggregatibacter aphrophilus to include V factor-dependent and V factor-independent isolates. Int. J. Syst. Evol. Microbiol. 56: 2135– 2146.
57. Novak, K. F.,, B. Dougherty, and, M. Pelaez. 2001. Actinobacillus actinomycetemcomitans harbours type IV secretion system genes on a plasmid and in the chromosome. Microbiology 147: 3027– 3035.
58. Novak, K. F.,, and D. J. LeBlanc. 1994. Characterization of plasmid pVT745 isolated from Actinobacillus actinomycetemcomitans. Plasmid 31: 31– 39.
59. Olivieri, A.,, A. Achilli,, M. Pala,, V. Battaglia,, S. Fornarino,, N. Al-Zahery,, R. Scozzari,, F. Cruciani,, D. M. Behar,, J. M. Dugoujon,, C. Coudray,, A. S. Santachiara-Benerecetti,, O. Semino,, H. J. Bandelt, and, A. Torroni. 2006. The mtDNA legacy of the Levantine early Upper Palaeolithic in Africa. Science 314: 1767– 1770.
60. Olsen, I.,, and K. Møller. 2005. Genus II. Actinobacillus Brumpt 1910, 849 AL, p. 866–883. In D. J. Brenner,, N. R. Krieg,, J. T. Staley, and, G. M. Garrity (ed.), Bergey’s Manual of Systematic Bacteriology, 2nd ed., vol. 2. The Proteobacteria, Part B, the Gammaproteobacteria. Springer, New York, NY.
61. Page, R. C.,, T. J. Sims,, L. D. Engel,, B. J. Monica,, B. Bainbridge,, J. Stray, and, R. P. Darveau. 1991. The immunodominant outer membrane antigen of Actinobacillus actinomycetemcomitans is located in the serotype-specific high-molecular-mass carbohydrate moiety of lipopolysaccharide. Infect. Immun. 59: 3451– 3462.
62. Planet, P. J.,, S. C. Kachlany,, D. H. Fine,, R. DeSalle, and, D. H. Figurski. 2003. The widespread colonization island of Actinobacillus actinomycetemcomitans. Nat. Genet. 34: 193– 198.
63. Potts, T. V.,, J. J. Zambon, and, R. J. Genco. 1985. Reassignment of Actinobacillus actinomycetemcomitans to the genus Haemophilus as Haemophilus actinomycetemcomitans comb. nov. Int. J. Syst. Bacteriol. 35: 337– 341.
64. Poulsen, K.,, O.-K. Ennibi, and, D. Haubek. 2003. Improved PCR for detection of the highly leukotoxic JP2 clone of Actinobacillus actinomycetemcomitans in subgingival plaque samples. J. Clin. Microbiol. 41: 4829– 4832.
65. Poulsen, K.,, E. Theilade,, E. T. Lally,, D. R. Demuth, and, M. Kilian. 1994. Population structure of Actinobacillus actinomycetemcomitans: a framework for studies of disease-associated properties. Microbiology 140: 2049– 2060.
66. Resch, G.,, E. M. Kulik,, F. S. Dietrich, and, J. Meyer. 2004. Complete genomic nucleotide sequence of the temperate bacteriophage Aa Phi 23 of Actinobacillus actinomycetemcomitans. J. Bacteriol. 186: 5523– 5528.
67. Rhodes, E. R.,, S. Menke,, C. Shoemaker,, A. P. Tomaras,, G. McGillivary, and, L. A. Actis. 2007. Iron acquisition in the dental pathogen Actinobacillus actinomycetemcomitans: what does it use as a source and how does it get this essential metal? Biometals 20: 365– 377.
68. Riep, B.,, L. Edesi-Neuß,, F. Claessen,, H. Skarabis,, B. Ehmke,, T. F. Flemming,, J.-P. Bernimoulin,, U. B. Göbel, and, A. Moter. 2009. Are putative periodontal pathogens reliable diagnostic markers? J. Clin. Microbiol. 47: 1705– 1711.
69. Rylev, M.,, and M. Kilian. 2008. Prevalence and distribution of principal periodontal pathogens worldwide. J. Clin. Periodontol. 35: 346– 361.
70. Sandmeier, H.,, A. J. van Winkelhoff,, K. Baer,, E. Ankli,, M. Maeder, and, J. Meyer. 1995. Temperate bacteriophages are common among Actinobacillus actinomycetemcomitans isolates from periodontal pockets. J. Periodontal Res. 30: 418– 425.
71. Schaeffer, L. M.,, M. L. Schmidt, and, D. R. Demuth. 2008. Induction of Aggregatibacter actinomycetemcomitans leukotoxin expression by IS 1301 and orfA. Microbiology 154: 528– 538.
72. Schreiner, H. C.,, K. Sinatra,, J. B. Kaplan,, D. Furgang,, S. C. Kachlany,, P. J. Planet,, B. A. Perez,, D. H. Figurski, and, D. H. Fine. 2003. Tight-adherence genes of Actinobacillus actinomycetemcomitans are required for virulence in a rat model. Proc. Natl. Acad. Sci. USA 100: 7295– 7300.
73. Seki, M.,, K. Poulsen,, D. Haubek, and, M. Kilian. 2008. Novel loop-mediated isothermal amplification method for detection of the JP2 clone of Aggregatibacter actinomycetemcomitans in subgingival plaque. J. Clin. Microbiol. 46: 1113– 1115.
74. Serruto, D.,, T. Spadafina,, M. Scarselli,, S. Bambini,, M. Comanducci,, S. Hoehle,, M. Kilian,, E. Veiga,, P. Cossart,, M. R. Oggioni,, S. Savino,, I. Ferlenghi,, A. R. Taddei,, R. Rappuoli,, M. Pizza,, V. Masignami, and, B. Arico. 2009. HadA is an atypical new multifunctional trimeric coiled-coil adhesin of Haemophilus influenzae biogroup aegyptius, which promotes entry into host cells. Cell. Microbiol. 11: 1044– 1063.
75. Slots, J.,, H. S. Reynolds, and, R. J. Genco. 1980. Actinobacillus actinomycetemcomitans in human periodontal disease: a cross-sectional microbiological investigation. Infect. Immun. 29: 1013– 1020.
76. Slots, J.,, and M. Ting. 1999. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontol. 2000 20: 82– 121.
77. Theilade, E. 1986. The non-specific theory in microbial etiology of inflammatory periodontal diseases. J. Clin. Periodontol. 13: 905– 911.
78. Tillier, E. R. M.,, and R. A. Collins. 2000. The contributions of replication orientation, gene direction, and signal sequences to base-composition asymmetries in bacterial genomes. J. Mol. Evol. 50: 249– 257.
79. Tomich, M.,, P. J. Planet, and, D. H. Figurski. 2007. The tad locus: postcards from the widespread colonization island. Nat. Rev. Microbiol. 5: 363– 375.
80. Tsai, C.-C.,, W. P. McArthur,, P. C. Baehni,, B. F. Hammond, and, N. S. Taichman. 1979. Extraction and partial characterization of leukotoxin from a plaque-derived gram-negative microorganism. Infect. Immun. 25: 427– 439.
81. Tsai, C. C.,, B. J. Shenker,, J. M. DiRienzo,, D. Malamud, and, N. S. Taichman. 1984. Extraction and isolation of a leukotoxin from Actinobacillus actinomycetemcomitans with polymyxin B. Infect. Immun. 43: 700– 705.
82. van Winkelhoff, A. J.,, and J. Slots. 1999. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in nonoral infections. Periodontol. 2000 20: 122– 135.
83. Wang, Y.,, S. D. Goodman,, R. J. Redfield, and, C. Chen. 2002. Natural transformation and DNA uptake signal sequences in Actinobacillus actinomycetemcomitans. J. Bacteriol. 184: 3442– 3449.
84. Wang, Y.,, A. Liu, and, C. Chen. 2005. Genetic basis for conversion of rough-to-smooth colony morphology in Actinobacillus actinomycetemcomitans. Infect. Immun. 73: 3749– 3753.
85. Willi, K.,, H. Sandmeier,, S. Asikainen,, M. Saarela, and, J. Meyer. 1997. Occurrence of temperate bacteriophages in different Actinobacillus actinomycetemcomitans serotypes isolated from periodontally healthy individuals. Oral Microbiol. Immunol. 12: 40– 46.
86. Wilson, M. E.,, and R. E. Schifferle. 1991. Evidence that the serotype b antigenic determinant of Actinobacillus actinomycetemcomitans Y4 resides in the polysaccharide moiety of lipopolysaccharide. Infect. Immun. 59: 1544– 1551.
87. Zambon, J. J. 1985. Actinobacillus actinomycetemcomitans in human periodontal disease. J. Clin. Periodontol. 12: 1– 20.
88. Zambon, J. J.,, V. I. Haraszthy,, G. Hariharan,, E. T. Lally, and, D. R. Demuth. 1996. The microbiology of early-onset periodontitis: association of highly toxic Actinobacillus actinomycetemcomitans strains with localized juvenile periodontitis. J. Periodontol. 67: 282– 290.

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