How we got attached to <i>Actinobacillus actinomycetemcomitans</i>: a model for infectious diseases

Fine, Daniel H.; Kaplan, Jeffrey B.; Kachlany, Scott C.; Schreiner, Helen

doi:10.1111/j.1600-0757.2006.00189.x

Cited by 136 publications

(167 citation statements)

References 316 publications

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“…Aggregatibacter (Actinobacillus) actinomycetemcomitans is a Gram-negative, facultative anaerobe of the Pasteurellaceae family that is found in the oral cavity (Henderson et al, 2003;Fine et al, 2006;Norskov-Lauritsen and Kilian, 2006). It is believed to cause localized aggressive periodontitis (LAP), a severe form of periodontal disease of adolescents, and several types of extraoral infections, including infective endocarditis, abscesses, meningitis, pneumonia, septicemia, urinary tract infections, and vertebral osteomyelitis (Zambon, 1985;Haffajee and Socransky, 1994;Slots, 1999;Henderson et al, 2003;Paturel et al, 2004;Fine et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…It is believed to cause localized aggressive periodontitis (LAP), a severe form of periodontal disease of adolescents, and several types of extraoral infections, including infective endocarditis, abscesses, meningitis, pneumonia, septicemia, urinary tract infections, and vertebral osteomyelitis (Zambon, 1985;Haffajee and Socransky, 1994;Slots, 1999;Henderson et al, 2003;Paturel et al, 2004;Fine et al, 2006). Fresh clinical isolates show a small, wrinkled (rough) colony form Henderson et al, 2003;Kachlany et al, 2001a).…”

Section: Introductionmentioning

confidence: 99%

“…Fresh clinical isolates show a small, wrinkled (rough) colony form Henderson et al, 2003;Kachlany et al, 2001a). The bacteria are known to produce several virulence factors, including a leukotoxin and a cytolethal distending toxin, and they adhere to solid surfaces and cells (Taichman and Wilton, 1981;Kolodrubetz et al, 1989;Lally et al, 1989;Eastcott et al, 1990;Mangan et al, 1991;Fives-Taylor et al, 1999;van Winkelhoff and Slots, 1999;Kachlany et al, 2001a;Narayanan et al, 2002;Henderson et al, 2003;Rose et al, 2003;Paturel et al, 2004;Rhodes et al, 2005;Diaz et al, 2006;Fine et al, 2005Fine et al, , 2006Smith and Bayles, 2006). Clinical isolates autoaggregate and secrete long, bundled pili (Flp fibrils) (Holt et al, 1980;Scannapieco et al, 1987;Rosan et al, 1988;Inoue et al, 1998;Kachlany et al, 2001b;Henderson et al, 2003;Fine et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The bacteria are known to produce several virulence factors, including a leukotoxin and a cytolethal distending toxin, and they adhere to solid surfaces and cells (Taichman and Wilton, 1981;Kolodrubetz et al, 1989;Lally et al, 1989;Eastcott et al, 1990;Mangan et al, 1991;Fives-Taylor et al, 1999;van Winkelhoff and Slots, 1999;Kachlany et al, 2001a;Narayanan et al, 2002;Henderson et al, 2003;Rose et al, 2003;Paturel et al, 2004;Rhodes et al, 2005;Diaz et al, 2006;Fine et al, 2005Fine et al, , 2006Smith and Bayles, 2006). Clinical isolates autoaggregate and secrete long, bundled pili (Flp fibrils) (Holt et al, 1980;Scannapieco et al, 1987;Rosan et al, 1988;Inoue et al, 1998;Kachlany et al, 2001b;Henderson et al, 2003;Fine et al, 2006). In vitro A. actinomycetemcomitans can produce rare, stable, nonadherent, and nonaggregative genetic variants that form smooth, large colonies and fail to produce Flp fibrils (Wyss, 1989;Inouye et al, 1990;Fine et al, 1999Fine et al, , 2006Kachlany et al, 2000Kachlany et al, , 2001aHenderson et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Clinical isolates autoaggregate and secrete long, bundled pili (Flp fibrils) (Holt et al, 1980;Scannapieco et al, 1987;Rosan et al, 1988;Inoue et al, 1998;Kachlany et al, 2001b;Henderson et al, 2003;Fine et al, 2006). In vitro A. actinomycetemcomitans can produce rare, stable, nonadherent, and nonaggregative genetic variants that form smooth, large colonies and fail to produce Flp fibrils (Wyss, 1989;Inouye et al, 1990;Fine et al, 1999Fine et al, , 2006Kachlany et al, 2000Kachlany et al, , 2001aHenderson et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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tfoX (sxy)-dependent transformation of Aggregatibacter (Actinobacillus) actinomycetemcomitans

Bhattacharjee

Fine

Figurski

2007

Gene

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AbstracttfoX (sxy) is a regulatory gene needed to turn on competence genes. Aggregatibacter (Actinobacillus) actinomycetemcomitans has a tfoX gene that is important for transformation. We cloned this gene on an IncQ plasmid downstream of the inducible tac promoter. When this plasmid was resident in cells of A. actinomycetemcomitans and tfoX was induced, the cells became competent for transformation. Several strains of A. actinomycetemcomitans, including different serotypes, as well as rough (adherent) and isogenic smooth (nonadherent) forms were tested. Only our two serotype f strains failed to be transformed. With the other strains, we could easily get transformants with extrachromosomal plasmid DNA when closed circular, replicative plasmid carrying an uptake signal sequence (USS) was used. When a replicative plasmid carrying a USS and cloned DNA from the chromosome of A. actinomycetemcomitans was linearized by digestion with a restriction endonuclease or when genomic DNA was used directly, the outcome was allelic exchange. To facilitate allelic exchange, we constructed a suicide plasmid (pMB78) that does not replicate in A. actinomycetemcomitans and carries a region with two inverted copies of a USS. This vector gave allelic exchange in the presence of cloned and induced tfoX easily and without digestion. Using transposon insertions in cloned katA DNA, we found that as little as 78 bp of homology at one of the ends was sufficient for that end to participate in allelic exchange. The cloning and induction of tfoX makes it possible to transform nearly any strain of A. actinomycetemcomitans, and allelic exchange has proven to be important for site-directed mutagenesis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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tfoX (sxy)-dependent transformation of Aggregatibacter (Actinobacillus) actinomycetemcomitans

Bhattacharjee

Fine

Figurski

2007

Gene

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High salivary levels of JP2 genotype of Aggregatibacter actinomycetemcomitans is associated with clinical attachment loss in Moroccan adolescents

Ennibi

Claesson

Akkaoui

et al. 2019

Clinical & Exp Dental Res

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It has previously been shown that the presence of Aggregatibacter actinomycetemcomitans in subgingival plaque is significantly associated with increased risk for clinical attachment loss. The highly leukotoxic JP2 genotype of this bacterium is frequently detected in adolescents with aggressive forms of periodontitis. The aims of the study were to quantify the levels of JP2 and non‐JP2 genotypes of A. actinomycetemcomitans in saliva of Moroccan adolescents with the JP2 genotype earlier detected in the subgingival plaque. The salivary concentrations of inflammatory proteins were quantified and linked to the clinical parameters and microbial findings. Finally, a mouth rinse with leukotoxin‐neutralizing effect was administrated and its effect on the levels the biomarkers and A. actinomycetemcomitans examined. The study population consisted of 22 adolescents that previously were found to be positive for the JP2 genotype in subgingival plaque. Periodontal registration and sampling of stimulated saliva was performed at baseline. A mouth rinse (active/placebo) was administrated, and saliva sampling repeated after 2 and 4 weeks rinse. The salivary levels of JP2 and non‐JP2 were analyzed by quantitative PCR and inflammatory proteins by ELISA. Both the JP2 and the non‐JP2 genotype were detected in all individuals with significantly higher levels of the non‐JP2. Enhanced levels of the JP2 genotype of A. actinomycetemcomitans was significantly correlated to the presence of attachment loss (≥3 mm). Salivary concentrations of inflammatory biomarkers did not correlate to periodontal condition or levels of A. actinomycetemcomitans . The use of active or placebo leukotoxin‐neutralizing mouth rinse did not significantly interfered with the levels of these biomarkers. Saliva is an excellent source for detection of A. actinomycetemcomitans on individual basis, and high levels of the JP2 genotype were significantly associated with the presence of clinical attachment loss.

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Solving the riddle: Unraveling the mechanisms of blocking the binding of leukotoxin by therapeutic antagonists in periodontal diseases

Abdullahi

Olotu

Soliman

2018

J of Cellular Biochemistry

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Aggregatibacter actinomycetemcomitans is a Gram-negative bacteria that has gained wide recognition for its causative role in the development of various immune diseases, which includes localized aggressive periodontitis. Its ability to evade host defense mechanisms is mediated by the secretion of leukotoxin (LtxA), which induces death of white blood cells (leukocytes) by specific binding to their surface-expressed leukocyte function-associated receptor (LFA-1) in its active state. Therapeutic compounds that interfere with this pathogenic process and abrogate A. actinomycetemcomitans virulence have been reported in literature. These include doxycycline, and more recently phytochemical compounds such as hamamelitanin, resveratrol, naringin, and quercetin. However, the question remains how do they work? Therefore, with the aid of computational tools, we explore the molecular mechanisms by which they possibly elicit their therapeutic functions. Molecular mechanics Poisson/Boltzmann surface area analyses revealed that these compounds bind favorably to active LFA-1 with high affinity and considerable stability, indicative of their ability to occupy the LtxA binding site (LBS) and prevent LtxA binding. The conformational transition of open LFA-1 to its closed state further describe the mechanistic activity of these compounds. In addition to notable reductions in structural mobility and flexibility, the burial of surface-exposed interactive side chains at the LBS was observed, an occurrence that could alter the complementary binding of LtxA. It is also important to mention that these occurrences were induced more prominently by the phytochemicals. We believe that these findings will enhance the scope of drug design and discovery for potent LtxA antagonists with improved activities and therapeutic efficacies in the treatment of virulent A. actinomycetemcomitans diseases.

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How we got attached to Actinobacillus actinomycetemcomitans: a model for infectious diseases

Cited by 136 publications

References 316 publications

tfoX (sxy)-dependent transformation of Aggregatibacter (Actinobacillus) actinomycetemcomitans

tfoX (sxy)-dependent transformation of Aggregatibacter (Actinobacillus) actinomycetemcomitans

High salivary levels of JP2 genotype of Aggregatibacter actinomycetemcomitans is associated with clinical attachment loss in Moroccan adolescents

Solving the riddle: Unraveling the mechanisms of blocking the binding of leukotoxin by therapeutic antagonists in periodontal diseases

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