Anaerobic neutrophil‐dependent killing of <i>Actinobacillus actinomycetemcomitans</i> in relation to the bacterial leukotoxicity

Johansson, Anders; Sandström, Gunnar; Claesson, Rolf; Hänström, Lennart; Kalfas, Sotirios

doi:10.1034/j.1600-0722.2000.00790.x

Cited by 50 publications

(63 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…actinomycetemcomitans LtxA is both secreted (18,19) and associated with the outer membrane of the cell (7,9,17,22). We show here that secretion of LtxA is required for hemolysis, since iron affects secretion but not ltxA synthesis.…”

mentioning

confidence: 71%

Regulation of Aggregatibacter ( Actinobacillus ) actinomycetemcomitans Leukotoxin Secretion by Iron

et al. 2006

View full text Add to dashboard Cite

The gram-negative oral and systemic pathogen Aggregatibacter (Actinobacillus) actinomycetemcomitans produces a leukotoxin (LtxA) that is a member of the RTX (repeats in toxin) family of secreted bacterial toxins. We have recently shown that LtxA has the ability to lyse erythrocytes, which results in a beta-hemolytic phenotype on Columbia blood agar. To determine if LtxA is regulated by iron, we examined beta-hemolysis under iron-rich and iron-limiting conditions. Beta-hemolysis was suppressed in the presence of FeCl 3 . In contrast, strong beta-hemolysis occurred in the presence of the iron chelator deferoxamine. We found that secretion of LtxA was completely inhibited by free iron, but expression of ltxA was not regulated by iron. Free chromium, cobalt, and magnesium did not affect LtxA secretion. Other LtxA-associated genes were not regulated by iron. Thus, iron appears to play an important role in the regulation of LtxA secretion in A. actinomycetemcomitans in a manner independent of gene regulation.

show abstract

mentioning

confidence: 71%

Regulation of Aggregatibacter ( Actinobacillus ) actinomycetemcomitans Leukotoxin Secretion by Iron

et al. 2006

View full text Add to dashboard Cite

show abstract

“…After 72 h incubation, the bacterial colonies were harvested with a sterile cotton swab and suspended in phosphate buffered saline (PBS), at pH 7.2. The concentration of bacteria in the suspensions were quantified by measuring the optical density (OD 600 nm ) and counting the colonies cultivated on blood agar plates [51].…”

Section: Bacterial Strainsmentioning

confidence: 99%

Aggregatibacter actinomycetemcomitans targets NLRP3 and NLRP6 inflammasome expression in human mononuclear leukocytes

Belibasakis

Johansson

2012

Cytokine

Self Cite

View full text Add to dashboard Cite

Periodontitis is an inflammatory condition that destroys the tooth-supporting tissues, as a result of local bacterial infection. Aggregatibacter actinomycetemcomitans is a Gram-negative facultative anaerobic species, highly associated with aggressive periodontitis. Periodontal inflammation is dominated by cytokines of the Interleukin (IL)-1 family. Prior to their secretion by mononuclear cells, IL-1 cytokines are processed by intracellular protein complexes, known as "inflammasomes", which can sense the bacterial challenge. The aim of this study was to investigate which inflammasomes are regulated in mononuclear cells in response to A. actinomycetemcomitans. The D7SS strain and its derivative leukotoxin and cytolethal distending toxin knock-out mutant strains were used to infect human mononuclear cells at a 1:10 cell: bacteria ratio, for 3 h. The expression of various inflammasome components in the cells was investigated by TaqMan quantitative real-time polymerase chain reaction (qPCR). The expressions of NOD-like receptor protein (NLRP)1, NLRP2 and Absent In Melanoma (AIM)2 inflammasome sensors, as well as their effector Caspase-1 were not affected. However, NLRP3 was up-regulated, while NLRP6 was down-regulated. This effect was not dependent on the leukotoxin or the cytolethal distending toxin, as demonstrated by the use of specific gene knock-out mutant strains. IL-1 and IL-18 expressions were also up-regulated by the bacterial challenge. In conclusion, A. actinomycetemcomitans enhances NLRP3 and reduces NLRP6 inflammasome expression, irrespective of its major virulence factors, confirming the high pathogenic profile of this species, and providing further insights to the mechanisms of periodontal inflammation. actinomycetemcomitans enhances NLRP3 and reduces NLRP6 inflammasome expression, irrespective of its major virulence factors, confirming the high pathogenic profile of this species, and providing further insights to the mechanisms of periodontal inflammation.

show abstract

“…While LtxA can be associated with the outer membrane (Ohta et al, 1991;Berthold et al, 1992;Johansson et al, 2000;Diaz et al, 2006), released within lipid vesicles (Kato et al, 2002;Demuth et al, 2003), and secreted from cells as soluble protein (Brogan et al, 1994;Kachlany et al, 2000), we believe that TdeA plays a role in all of these processes. Because RTX toxins are transported through the bacterial cell envelope without a periplasmic intermediate (Gray et al, 1986;Koronakis et al, 2004), LtxA would have to be exported through TdeA before localizing to the outer membrane or within vesicles.…”

Section: Discussionmentioning

confidence: 78%

TdeA, a TolC-like protein required for toxin and drug export in Aggregatibacter (Actinobacillus) actinomycetemcomitans

Crosby

Kachlany

2007

Gene

View full text Add to dashboard Cite

Aggregatibacter actinomycetemcomitansW is an oral bacterium that causes localized aggressive periodontitis (LAP) and extra-oral infections such as sub-acute infective endocarditis. As part of its array of virulence factors, A. actinomycetemcomitans produces leukotoxin (LtxA), a member of the RTX family of toxins. LtxA kills human leukocytes and we have recently shown that the toxin is required for β -hemolysis by A. actinomycetemcomitans on solid medium. In other RTX toxinproducing bacteria, an outer membrane channel-forming protein, TolC, is required for toxin secretion and drug export. We have identified an ORF in A. actinomycetemcomitans that encodes a putative protein having predicted structural properties similar to TolC. Inactivation of this ORF resulted in a mutant that was no longer β -hemolytic and did not secrete LtxA. This mutant was significantly more sensitive to antimicrobial agents compared to the wild type strain and was unable to export the antimicrobial agent berberine. Thus, this ORF was named tdeA for "toxin and drug export". Examination of the DNA sequence surrounding tdeA revealed two upstream ORFs that encode proteins similar to the drug efflux proteins, MacA and MacB. Inactivation of macB in A. actinomycetemcomitans did not alter the drug sensitivity profile or the hemolytic activity of the mutant. The genes macA, macB and tdeA are organized as an operon and are constitutively expressed as a single transcript. These results show that A. actinomycetemcomitans indeed requires a TolC-like protein for LtxA secretion and that this protein, TdeA, also functions as part of a drug efflux system.

show abstract

Anaerobic neutrophil‐dependent killing of Actinobacillus actinomycetemcomitans in relation to the bacterial leukotoxicity

Cited by 50 publications

References 26 publications

Regulation of Aggregatibacter ( Actinobacillus ) actinomycetemcomitans Leukotoxin Secretion by Iron

Regulation of Aggregatibacter ( Actinobacillus ) actinomycetemcomitans Leukotoxin Secretion by Iron

Aggregatibacter actinomycetemcomitans targets NLRP3 and NLRP6 inflammasome expression in human mononuclear leukocytes

TdeA, a TolC-like protein required for toxin and drug export in Aggregatibacter (Actinobacillus) actinomycetemcomitans

Contact Info

Product

Resources

About