Non-virulent Porphyromonas gingivalis mutant

Details Non-virulent Porphyromonas gingivalis mutant Non-virulent Porphyromonas gingivalis mutant

2001-03-12

2003-07-01

Kunz, Gary (Department: 1647)

Chemistry: molecular biology and microbiology

Micro-organism, per se ; compositions thereof; proces of...

Bacteria or actinomycetales; media therefor

C435S471000, C424S093100, C424S093200

Reexamination Certificate

active

06586227

ABSTRACT:

BACKGROUND
Periodontitis is an inflammatory disease of the tissues surrounding the teeth characterized by loss of the periodontal ligament attachment and alveolar bone support of the tooth. Periodontitis affects more than 49 million people in the United States and hundreds of millions of people worldwide and has been reported as a risk factor for cardiovascular disease and pre-term delivery of low-birth-weight infants. The most common cause of periodontitis is chronic Gram-negative bacterial infections. Among the Gram-negative bacteria implicated as a cause of periodontitis,
Porphyromonas gingivalis
is the major component of the flora in over 90% of adult periodontitis lesions.
Besides being a major etiological agent in adult human periodontitis,
Porphyromonas gingivalis
also causes aspiration pneumonia and necrotizing pneumonia, abscesses in brain, genitourinary tract and lung, as well as mediastinitis. By contrast,
P. gingivalis
is not normally found at healthy sites nor is it found in patients with gingivitis but with no accompanying periodontitis.
The current therapy for periodontitis is directed toward identifying, removing and controlling the etiologic factors, and then correcting the defects these pathogens have caused. These therapies include scaling and root planing, chemotherapy, periodontal surgery and periodic maintenance therapy. However, these treatments are not entirely effective because, for example, the pathogens can become resistant to chemotherapeutic agents.
Several potential virulence factors have been identified which appear to relate to the pathogenicity of
P. gingivalis
in periodontitis. These factors include fimbriae (adhesins), capsule (antiphagocytosis), lipopolysaccharide (bone resorption), proteases (specific and generalized tissue destruction) and a variety of toxic by-products (e.g., ammonia). Some of these factors have been purified and biochemically characterized. However, the specific roles, interactions, relative importance and regulation of these factors remains to be determined.
Therefore, there remains a need for effective prevention and treatment for periodontitis. Further, there remains a need for a modified strain of
P. gingivalis
that can be used as a host genetic background to determine the specific roles, interactions, relative importance and regulation of the potential virulence factors produced by wild-type
P. gingivalis.
SUMMARY
According to one embodiment of the present invention, there is provided a nonvirulent, recA defective mutant of
Porphyromonas gingivalis.
According to another embodiment of the present invention, there is provided a
Porphyromonas gingivalis
strain which is deposited at ATCC under accession number 202109.
According to another embodiment of the present invention, there is provided a pharmaceutical preparation comprising a mutant of
Porphyromonas gingivalis
according to the present invention.
According to another embodiment of the present invention, there is provided a method of decreasing the growth rate or reproduction rate of
Porphyromonas gingivalis
in a mammal, such as a human. The method comprises the step of administering to the mammal at least one dose of a non-virulent, recA defective mutant of
Porphyromonas gingivalis,
such as at least one dose of a
Porphyromonas gingivalis
strain which is deposited at ATCC under accession number 202109.
According to another embodiment of the present invention, there is provided a method of preventing or treating a
Porphyromonas gingivalis
infection such as periodontitis in a mammal, such as a human. The method comprises the step of administering to the mammal at least one dose of
Porphyromonas gingivalis
according to the present invention.
The methods of the present invention can be performed by administering to the mutant with the at least one dose of a non-virulent, recA defective mutant of
Porphyromonas gingivalis
via a route selected from the group consisting of a subcutaneous route, an intravenous route and an intramuscular route, among other routes. In a preferred embodiment, the methods of the present invention include administering at least one dose of a non-virulent, recA defective mutant of
Porphyromonas gingivalis
, wherein the dose is between about a 1×10
3
and 1×10
7
bacteria per kg of body weight of the mammal. More preferably, the dose is between about 1×10
5
and 1×10
6
bacteria per kg of body weight of the mammal.


REFERENCES:
patent: 6254863 (2001-07-01), Fletcher
Abaibou, H. et al., “A gene in the recA locus affects the virulence potential ofPorphyromonas gingivalisW83,” Abstract,Periodontal Research, p. 232; Cover page of the Journal of Dental Research, vol. 79, Apr. 5-8, 2000.
Aduse-Opoku, Joseph et al., “Characterization, Genetic Analysis, and Expression of a Protease Antigen (PrpRI) ofPorphyromonas gingivalisW50,”Infection and Immunity63(12):4744-4754 (1995).
Anderson, D.M. et al., “Functional Properties of Nonhuman Primate Antibody toPorphyromonas gingivalis,”Infection and Immunity63(9):3245-3252 (1995).
Barkocy-Gallagher, Genevieve A. et al., “Analysis of the prtP Gene Encoding Porphypain, a Cysteine Proteinase ofPorphyromonas gingivalis,”Journal of Bacteriology178(10):2734-2741 (1996).
Beck, James et al., “Periodontal Disease and Cardiovascular Disease,”J Periodontol67(10):1123-1137 (1996).
Booth, V. et al., “Passive Immunization with Monoclonal Antibodies againstPorphyromonas gingivalisin Patients with Periodontitis,”Infection and Immunity64(2):422-427 (1996).
Chen, Priscilla B. et al., “Effect of Immunization on ExperimentalBacteroides gingivalis,”Infection and Immunity, 55(10):2534-2537 (Oct. 1987).
Christersson, L.A. et al., “Specific Subgingival Bacteria and Diagnosis of Gingivitis and Periodontitis,”J Dent Res68:1633-1639 (1989).
Devereux, John et al., “A comprehensive set of sequence analysis programs for the VAX,”Nucleic Acids Research12(1):387-395 (1984).
Dickinson, Douglas P. et al., “Molecular Cloning and Sequencing of the Gene Encoding the Fimbrial Subunit Protein Protein ofBacteroides gingivalis,”Journal of Bacteriology170(4):1658-1665 (1988).
Dusek, David M. et al., “Systemic and Mucosal Immune Responses in Mice Orally Immunized with AvirulentSalmonella typhimuriumExpressing a ClonedPorphyromonas gingivalisHemagglutinin,”Infection and Immunity62(5):1652-1657 (1994).
Dybvig, Kevin et al., “Degenerate Oligonucleotide Primers for Enzymatic Amplification of recA Sequences from Gram-Positive Bacteria and Mycoplasmas,”Journal of Bacteriology174(8):2729-2732 (1992).
Dzink J.L. et al., “The predominant cultivable microbiota of active and inactive lesions of destructive periodontal diseases,”J Clin Periodontal15:316-323 (1988).
Fletcher, Hansel M. et al., “Virulence of aPorphyromonas gingivalisW83 Mutant Defective in the prtH Gene,”Infection and Immunity63(4):1521-1528 (1995).
Fletcher, Hansel M. et al., “Nucleotide Sequence of thePorphyromonas gingivalisW83 recA Homolog and Construction of a recA-Deficient Mutant,”Infection and Immunity65(1):4592-4597 (1997).
Fletcher et al, Cloning and sequencing of a recA-like gene fromPorphyromonas gingivalisW83,J. Dent Res, vol. 76, IADR abstract 1104, p. 151, Nov. 1997.
Fletcher, H.M., Virulence of recA-defective mutants ofPorphyromonas gingivalisW83,Abstracts of the 97th General Meeting of the American Society for Microbiology, abstract B-424, p. 101, Miami Beach, Florida, May 4-8, 1997.
Genco, C.A. et al., “Characterization of a Tn4351-Generated Hemin Uptake Mutant ofPorphyromonas gingivalis: Evidence for the Coordinate Regulation of Virulence Factors by Hemin,” 63(7):2459-2466 (1995).
Genco, C.A. et al., “A Peptide Domain on Gingipain R Which Confers Immunity againstPorphyromonas gingivalisInfection in Mice,”Infection and Immunity, 66(9):4108-4114 (Sep. 1998).
Goodman, Heide J.K. et al., “Molecular analysis of theBacteroides fragilis recAgene,”Gene94:77-82 (1990).
Hamada, Nobushiro et al., “Construction and Characterization of a fimA Mutant ofPorphyromonas gingivalis,”Infection and Immunity62(5):1696-1704 (1994).
Hoover, Charles I. e

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