Resistance of fluorescent-labelled Actinobacillus actinomycetemcomitans strains to phagocytosis and killing by human neutrophils

Permpanich, Piyanuj; Kowolik, Michael; Galli, Dominique M.

doi:10.1111/j.1462-5822.2005.00601.x

Cited by 41 publications

(47 citation statements)

References 54 publications

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“…Phagocytosis by neutrophils is a major host defense mechanism for bacterial clearance in the gingival sulcus (25,26). However, previous in vitro studies found A. actinomycetemcomitans to be relatively resistant to phagocytosis (38,41,52). The MCP-1 and MCP-2 host defense peptides (currently known as ␤-defensin A and B) were shown to act as opsonins and to enhance the ability of rabbit alveolar macrophages to ingest Staphylococcus aureus, Klebsiella pneumoniae, Bordetella bronchiseptica, and Candida albicans (45).…”

Section: Resultsmentioning

confidence: 96%

“…Aggregatibacter actinomycetemcomitans ATCC 29523, JP2, and Y4 were cultured in 0.5% yeast extract, 1.5% Bacto tryptone, 0.75% D-glucose, 0.25% NaCl, 0.075% L-cysteine, 0.05% sodium thioglycolate, and 4% NaHCO 3 . Strains VT726S, VT726S Ltx Ϫ (a kind gift of D. Galli), and ATCC 33384 (a kind gift of U. K. Gursoy) (38) were cultured in tryptic soy broth supplemented with 0.6% yeast extract (TSBYE medium). Kanamycin (100 g/ml) was added for growth of the leukotoxin-deficient strain VT726S Ltx Ϫ .…”

Section: Methodsmentioning

confidence: 99%

“…Some reported efficient phagocytosis and killing (37), while others found complement-mediated phagocytosis of A. actinomycetemcomitans to be generally inefficient and uptake of antibody-opsonized bacteria to result in the rapid cell death of neutrophils (38). Oral A. actinomycetemcomitans strains were divided into seven serotypes, a, b, c, d, e, f, and g (39,40).…”

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confidence: 99%

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LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

et al. 2013

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Host defense peptides are immediate responders of the innate immunity that express antimicrobial, immunoregulatory, and wound-healing activities. Neutrophils are a major source for oral host defense peptides, and phagocytosis by neutrophils is a major mechanism for bacterial clearance in the gingival tissue. Dysfunction of or reduction in the numbers of neutrophils or deficiency in the LL-37 host defense peptide was each previously linked with proliferation of oral Aggregatibacter actinomycetemcomitans which resulted in an aggressive periodontal disease. Surprisingly, A. actinomycetemcomitans shows resistance to high concentrations of LL-37. In this study, we demonstrated that submicrocidal concentrations of LL-37 inhibit biofilm formation by A. actinomycetemcomitans and act as opsonins and agglutinins that greatly enhance its clearance by neutrophils and macrophages. Improved uptake of A. actinomycetemcomitans by neutrophils was mediated by their opsonization with LL-37. Enhanced phagocytosis and killing of A. actinomycetemcomitans by murine macrophage-like RAW 264.7 cells were dependent on their preagglutination by LL-37. Although A. actinomycetemcomitans is resistant to the bactericidal effect of LL-37, our results offer a rationale for the epidemiological association between LL-37 deficiency and the expansion of oral A. actinomycetemcomitans and indicate a possible therapeutic use of cationic peptides for host defense.

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Section: Resultsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

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“…Examination of gingival crevicular fluid or saliva in persons with LAP may address this issue. Also, bacterial cells can interact directly with neutrophils, and thus, cell-bound LtxA would be important for mediating cell death via direct contact (Permpanich et al, 2006).…”

Section: Interaction With Host Cellsmentioning

confidence: 99%

Aggregatibacter actinomycetemcomitans Leukotoxin

2010

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Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium that colonizes the human oral cavity and is the causative agent for localized aggressive periodontitis (LAP), an aggressive form of periodontal disease that occurs in adolescents. A. actinomycetemcomitans secretes a protein toxin, leukotoxin (LtxA), which helps the bacterium evade the host immune response during infection. LtxA is a membrane-active toxin that specifically targets white blood cells (WBCs). In this review, we discuss recent developments in this field, including the identification and characterization of genes and proteins involved in secretion, regulation of LtxA, biosynthesis, newly described activities of LtxA, and how LtxA may be used as a therapy for the treatment of diseases.

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“…At high concentrations, leukotoxin can destroy human leukocytes by forming pores in host cell membranes and by disruption of mitochondrion function, leading to apoptosis (5,8,11,12,13). At low concentrations of leukotoxin, there is apoptosis and neutrophil degranulation, including the release of the collagenolytic matrix metalloproteinase MMP-8 (14), and phagocytosis can be inhibited (15). All of these results are consistent with a role for leukotoxin as a key player in modulating the host immune response to A. actinomycetemcomitans and possibly other bacteria found at the same sites.…”

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confidence: 99%

Mlc Is a Transcriptional Activator with a Key Role in Integrating Cyclic AMP Receptor Protein and Integration Host Factor Regulation of Leukotoxin RNA Synthesis in Aggregatibacter actinomycetemcomitans

et al. 2013

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Aggregatibacter actinomycetemcomitans, a periodontal pathogen, synthesizes leukotoxin (LtxA), a protein that helps the bacterium evade the host immune response. Transcription of the ltxA operon is induced during anaerobic growth. The cyclic AMP (cAMP) receptor protein (CRP) indirectly increases ltxA expression, but the intermediary regulator is unknown. Integration host factor (IHF) binds to and represses the leukotoxin promoter, but neither CRP nor IHF is responsible for the anaerobic induction of ltxA RNA synthesis. Thus, we have undertaken studies to identify other regulators of leukotoxin transcription and to demonstrate how these proteins work together to modulate leukotoxin synthesis. First, analyses of ltxA RNA expression from defined leukotoxin promoter mutations in the chromosome identify positions ؊69 to ؊35 as the key control region and indicate that an activator protein modulates leukotoxin transcription. We show that Mlc, which is a repressor in Escherichia coli, functions as a direct transcriptional activator in A. actinomycetemcomitans; an mlc deletion mutant reduces leukotoxin RNA synthesis, and recombinant Mlc protein binds specifically at the ؊68 to ؊40 region of the leukotoxin promoter. Furthermore, we show that CRP activates ltxA expression indirectly by increasing the levels of Mlc. Analyses of ⌬mlc, ⌬ihf, and ⌬ihf ⌬mlc strains demonstrate that Mlc can increase RNA polymerase (RNAP) activity directly and that IHF represses ltxA RNA synthesis mainly by blocking Mlc binding. Finally, a ⌬ihf ⌬mlc mutant still induces ltxA during anaerobic growth, indicating that there are additional factors involved in leukotoxin transcriptional regulation. A model for the coordinated regulation of leukotoxin transcription is presented.

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Resistance of fluorescent-labelled Actinobacillus actinomycetemcomitans strains to phagocytosis and killing by human neutrophils

Cited by 41 publications

References 54 publications

LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

Aggregatibacter actinomycetemcomitans Leukotoxin

Mlc Is a Transcriptional Activator with a Key Role in Integrating Cyclic AMP Receptor Protein and Integration Host Factor Regulation of Leukotoxin RNA Synthesis in Aggregatibacter actinomycetemcomitans

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