Structure/Function Aspects of Actinobacillus actinomycetemcomitans Leukotoxin.

Actinobacillus actinomycetemcomitans has been implicated as a causative organism in early-onset periodontitis. The mechanisms by which A. actinomycetemcomitans is pathogenic are not known, but the organism produces several potential virulence factors, one of which is a leukotoxin. As a group, bacterial protein toxins are made up of structural domains which control various aspects of toxic activity, such as target cell recognition, membrane insertion, and killing. The purpose of this article is to review the structure of RTX, with special emphasis to its relation to toxin function. In addition, we will propose a model based upon other bacterial proteins whereby the water-soluble A. actinomycetemcomitans leukotoxin is able to achieve insertion into a biological membrane. J Periodontol 1996;67:298-308.

[1]  E. Lally,et al.  The Microbiology of Early-Onset Periodontitis: Association of Highly Toxic Actinobacillus actinomycetemcomitans Strains With Localized Juvenile Periodontitis. , 1996, Journal of periodontology.

[2]  E. T. Lally,et al.  Actinobacillus actinomycetemcomitans leukotoxin forms large conductance, voltage-gated ion channels when incorporated into planar lipid bilayers. , 1995, Biochimica et biophysica acta.

[3]  P. Stanley,et al.  Fatty acylation of two internal lysine residues required for the toxic activity of Escherichia coli hemolysin. , 1994, Science.

[4]  E. Lally,et al.  Identification and immunological characterization of the domain of Actinobacillus actinomycetemcomitans leukotoxin that determines its specificity for human target cells. , 1994, The Journal of biological chemistry.

[5]  A. Finkelstein,et al.  Identification of a translocated protein segment in a voltage-dependent channel , 1994, Nature.

[6]  R. Welch,et al.  Pore-formation by Escherichia coli hemolysin (HlyA) and other members of the RTX toxins family. , 1994, Toxicology.

[7]  R. Welch,et al.  Analysis of toxinogenic functions associated with the RTX repeat region and monoclonal antibody D12 epitope of Escherichia coli hemolysin , 1994, Infection and immunity.

[8]  M. Parker,et al.  Rendering a membrane protein soluble in water: a common packing motif in bacterial protein toxins. , 1993, Trends in biochemical sciences.

[9]  U. Baumann,et al.  Three‐dimensional structure of the alkaline protease of Pseudomonas aeruginosa: a two‐domain protein with a calcium binding parallel beta roll motif. , 1993, The EMBO journal.

[10]  Janet M. Thornton,et al.  Protein fold recognition , 1993, J. Comput. Aided Mol. Des..

[11]  D. T. Jones,et al.  A new approach to protein fold recognition , 1992, Nature.

[12]  D. Russell,et al.  Expression cloning of a diphtheria toxin receptor: Identity with a heparin-binding EGF-like growth factor precursor , 1992, Cell.

[13]  Katherine A. Kantardjieff,et al.  The crystal structure of diphtheria toxin , 1992, Nature.

[14]  E. London,et al.  Diphtheria toxin: membrane interaction and membrane translocation. , 1992, Biochimica et biophysica acta.

[15]  J. Rosenbloom,et al.  Electron immunocytochemical localization of Actinobacillus actinomycetemcomitans leukotoxin. , 1992, Oral microbiology and immunology.

[16]  D. Struck,et al.  Separable domains define target cell specificities of an RTX hemolysin from Actinobacillus pleuropneumoniae , 1992, Journal of bacteriology.

[17]  J. Lakey,et al.  A 'molten-globule' membrane-insertion intermediate of the pore-forming domain of colicin A , 1991, Nature.

[18]  D. Ellar,et al.  Crystal structure of insecticidal δ-endotoxin from Bacillus thuringiensis at 2.5 Å resolution , 1991, Nature.

[19]  P. Stanley,et al.  Mutational analysis supports a role for multiple structural features in the C‐terminal secretion signal of Escherichia coli haemolysin , 1991, Molecular microbiology.

[20]  D. Tsernoglou,et al.  A common channel-forming motif in evolutionarily distant porins. , 1991, Journal of structural biology.

[21]  K. Hardie,et al.  In vitro activation of Escherichia coli prohaemolysin to the mature membrane‐targeted toxin requires HlyC and a low molecular‐weight cytosolic polypeptide , 1991, Molecular microbiology.

[22]  J. Issartel,et al.  Activation of Escherichia coli prohaemolysin to the mature toxin by acyl carrier protein-dependent fatty acylation , 1991, Nature.

[23]  H. Mobley,et al.  Cytotoxicity of the HpmA hemolysin and urease of Proteus mirabilis and Proteus vulgaris against cultured human renal proximal tubular epithelial cells , 1991, Infection and immunity.

[24]  J. Rosenbloom,et al.  Actinobacillus actinomycetemcomitans leukotoxin is a calcium-binding protein. , 1991, Journal of periodontal research.

[25]  R. Welch.  Pore‐forming cytolysins of Gram‐negative bacteria , 1991, Molecular microbiology.

[26]  D. Struck,et al.  Deletion analysis resolves cell‐binding and lytic domains of the Pasteurella leukotoxin , 1990, Molecular microbiology.

[27]  P. Delepelaire,et al.  Protein secretion in gram-negative bacteria. The extracellular metalloprotease B from Erwinia chrysanthemi contains a C-terminal secretion signal analogous to that of Escherichia coli alpha-hemolysin. , 1990, The Journal of biological chemistry.

[28]  R. Welch,et al.  Domains of Escherichia coli hemolysin (HlyA) involved in binding of calcium and erythrocyte membranes , 1990, Infection and immunity.

[29]  S. Létoffé,et al.  Protease secretion by Erwinia chrysanthemi: the specific secretion functions are analogous to those of Escherichia coli alpha‐haemolysin. , 1990, The EMBO journal.

[30]  H. Höfte,et al.  Receptors on the brush border membrane of the insect midgut as determinants of the specificity of Bacillus thuringiensis delta-endotoxins , 1990, Applied and environmental microbiology.

[31]  D. Tsernoglou,et al.  Insights into membrane insertion based on studies of colicins. , 1990, Trends in biochemical sciences.

[32]  R. Lo.  Molecular characterization of cytotoxins produced by Haemophilus, Actinobacillus, Pasteurella. , 1990, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.

[33]  D. Tsernoglou,et al.  Colicins: prokaryotic killer-pores. , 1990, Experientia.

[34]  A. Filloux,et al.  Cloning of the Pseudomonas aeruginosa alkaline protease gene and secretion of the protease into the medium by Escherichia coli , 1990, Journal of bacteriology.

[35]  H. Höfte,et al.  Specificity of Bacillus thuringiensis delta-endotoxins. Importance of specific receptors on the brush border membrane of the mid-gut of target insects. , 1989, European journal of biochemistry.

[36]  J. MacInnes,et al.  Molecular cloning and characterization of a hemolysin gene from Actinobacillus (Haemophilus) pleuropneumoniae , 1989, Infection and immunity.

[37]  J. Rosenbloom,et al.  Analysis of the Actinobacillus actinomycetemcomitans leukotoxin gene. Delineation of unique features and comparison to homologous toxins. , 1989, The Journal of biological chemistry.

[38]  T. McDonald,et al.  Identification of a hemolysin from Actinobacillus pleuropneumoniae and characterization of its channel properties in planar phospholipid bilayers. , 1989, The Journal of biological chemistry.

[39]  H. R. Whiteley,et al.  Insecticidal crystal proteins of Bacillus thuringiensis. , 1989, Microbiological reviews.

[40]  N. Taichman,et al.  Intra-oral colonization of macaque monkeys by Actinobacillus actinomycetemcomitans. , 1989, Oral microbiology and immunology.

[41]  W. Goebel,et al.  Pore formation by the Escherichia coli hemolysin: evidence for an association-dissociation equilibrium of the pore-forming aggregates , 1989, Infection and immunity.

[42]  J. Rosenbloom,et al.  Identification and expression of the Actinobacillus actinomycetemcomitans leukotoxin gene. , 1989, Biochemical and biophysical research communications.

[43]  C. Strathdee,et al.  Cloning, nucleotide sequence, and characterization of genes encoding the secretion function of the Pasteurella haemolytica leukotoxin determinant , 1989, Journal of bacteriology.

[44]  V. Koronakis,et al.  Isolation and analysis of the C‐terminal signal directing export of Escherichia coli hemolysin protein across both bacterial membranes. , 1989, The EMBO journal.

[45]  D. Tsernoglou,et al.  Structure of the membrane-pore-forming fragment of colicin A , 1989, Nature.

[46]  A. Danchin,et al.  Secretion of cyclolysin, the calmodulin‐sensitive adenylate cyclase‐haemolysin bifunctional protein of Bordetella pertussis. , 1988, The EMBO journal.

[47]  C. Hofmann,et al.  Specificity of Bacillus thuringiensis delta-endotoxins is correlated with the presence of high-affinity binding sites in the brush border membrane of target insect midguts. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[48]  V. Géli,et al.  The membrane channel-forming colicin A: synthesis, secretion, structure, action and immunity. , 1988, Biochimica et biophysica acta.

[49]  E. Golub,et al.  A computer graphics program system for protein structure representation. , 1988, Nucleic acids research.

[50]  S. Sakurada,et al.  Comparative studies on the biology of Actinobacillus actinomycetemcomitans leukotoxin in primates. , 1987, Oral microbiology and immunology.

[51]  R. Welch.  Identification of two different hemolysin determinants in uropathogenic Proteus isolates , 1987, Infection and immunity.

[52]  N. Mackman,et al.  Escherichia coli hemolysin may damage target cell membranes by generating transmembrane pores , 1986, Infection and immunity.

[53]  C. Strathdee,et al.  Cloning and expression of the leukotoxin gene of Pasteurella haemolytica A1 in Escherichia coli K-12 , 1985, Infection and immunity.

[54]  E. Lally,et al.  Monoclonal antibodies to leukotoxin of Actinobacillus actinomycetemcomitans , 1985, Infection and immunity.

[55]  L. Glickman,et al.  Cytopathic effects of Actinobacillus actinomycetemcomitans on monkey blood leukocytes. , 1984, Journal of periodontal research.

[56]  S. Falkow,et al.  Molecular cloning and physical characterization of a chromosomal hemolysin from Escherichia coli , 1983, Infection and immunity.

[57]  R. Genco,et al.  Serology of oral Actinobacillus actinomycetemcomitans and serotype distribution in human periodontal disease , 1983, Infection and immunity.

[58]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[59]  R. Dean,et al.  Biochemical and morphological characterization of the killing of human monocytes by a leukotoxin derived from Actinobacillus actinomycetemcomitans , 1980, Infection and immunity.

[60]  P. Y. Chou,et al.  Conformational parameters for amino acids in helical, beta-sheet, and random coil regions calculated from proteins. , 1974, Biochemistry.

[61]  C. Yoran,et al.  Actinobacillus actinomycetemcomitans endocarditis: report of a case and review of the literature. , 1973, The American journal of the medical sciences.

[62]  M I Page,et al.  Infection due to Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus. , 1966, The New England journal of medicine.

[63]  J. Skehel,et al.  The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. , 1987, Annual review of biochemistry.

[64]  S. Bhakdi,et al.  Damage to mammalian cells by proteins that form transmembrane pores. , 1987, Reviews of physiology, biochemistry and pharmacology.

[65]  J. Zambon.  Actinobacillus actinomycetemcomitans in human periodontal disease. , 1985, Journal of clinical periodontology.

[66]  J. Konisky,et al.  Colicins and other bacteriocins with established modes of action. , 1982, Annual review of microbiology.

[67]  W. Mcarthur,et al.  Leukotoxic activity in different strains of the bacterium Actinobacillus actinomycetemcomitans isolated from juvenile periodontitis in man. , 1981, Archives of oral biology.