Interaction of Actinobacillus actinomycetemcomitans outer membrane vesicles with HL60 cells does not require leukotoxin

Demuth, Donald R.; James, Deanna; Kowashi, Yusuke; Kato, Soushi

doi:10.1046/j.1462-5822.2003.00259.x

Cited by 64 publications

(73 citation statements)

References 56 publications

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“…Outer membrane vesicles (OMVs) released by this organism carry multiple proteins, and density gradient centrifugation supports the notion that there may be subpopulations of vesicles exhibiting slight variations in protein composition (7,19). Further to earlier reports revealing the OMV association of leukotoxin (LtxA) and a concomitant leukotoxic activity of A. actinomycetemcomitans OMVs (19,20), we have demonstrated that the OMVs could simultaneously deliver multiple proteins, including OmpA and biologically active cytolethal distending toxin (CDT), into HeLa cells and human gingival fibroblasts (HGF) (7). Hence, OMVs released by this species likely play a role in periodontal disease by delivering biologically active toxins and additional virulence factors into susceptible cells of the periodontium.…”

supporting

confidence: 73%

Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles Are Internalized in Human Host Cells and Trigger NOD1- and NOD2-Dependent NF-κB Activation

et al. 2014

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supporting

confidence: 73%

Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles Are Internalized in Human Host Cells and Trigger NOD1- and NOD2-Dependent NF-κB Activation

et al. 2014

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“…In contrast, although leukotoxin is associated with the surface of A. actinomycetemcomitans OM vesicles, the toxin is not responsible for the adherence of the vesicles with HL60 human myeloid leukemia cells (Demuth et al 2003). After a brief, 2-min incubation, A. actinomycetemcomitans OM vesicle antigens are found around the periphery of the cells.…”

Section: Adherence and Entry Into Host Cells And Tissuesmentioning

confidence: 87%

Bacterial outer membrane vesicles and the host–pathogen interaction

Kuehn¹,

Kesty²

2005

Genes Dev.

784

725

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Extracellular secretion of products is the major mechanism by which Gram-negative pathogens communicate with and intoxicate host cells. Vesicles released from the envelope of growing bacteria serve as secretory vehicles for proteins and lipids of Gram-negative bacteria. Vesicle production occurs in infected tissues and is influenced by environmental factors. Vesicles play roles in establishing a colonization niche, carrying and transmitting virulence factors into host cells, and modulating host defense and response. Vesicle-mediated toxin delivery is a potent virulence mechanism exhibited by diverse Gram-negative pathogens. The biochemical and functional properties of pathogen-derived vesicles reveal their potential to critically impact disease.In nearly every case, virulence factors of Gram-negative pathogens are secreted products that enhance the survival of the bacteria and/or damage the host. Secretion of virulence factors by Gram-negative pathogens is complicated by the fact that the bacterial envelope consists of two lipid bilayers, the inner and outer membrane, and the periplasm in between. Gram-negative pathogens have developed many strategies, some specific to pathogens, to enable active virulence factors to gain access to the extracellular environment, typically the tissues or bloodstream of the host organism (Henderson et al. 2004). The Type II and Type V secretion systems are two-step processes in which proteins are transported first through the inner membrane (IM) and then through the outer membrane (OM). For secretion via the Type I, Type III, and Type IV secretion systems, the material is transferred directly into the extracellular milieu or into another cell. The Type III system is specific for the transport of factors by pathogenic bacteria. All of these secretion systems secrete individual proteins or small complexes. This review examines secretion via OM vesicles, a distinct "Type VI" mechanism that enables bacteria to secrete a large, complex group of proteins and lipids into the extracellular milieu.Both pathogenic and nonpathogenic species of Gram- Vesicles are a means by which bacteria interact with prokaryotic and eukaryotic cells in their environment. Some of the best-characterized vesicles are those produced by pathogens. Biochemical analysis and functional characterization of pathogen-derived outer membrane vesicles demonstrate that this secretory pathway has been usurped by pathogens for the transport of active virulence factors to host cells (Table 1). Naturally produced OM vesicles from pathogenic bacteria contain adhesins, toxins, and immunomodulatory compounds, and they directly mediate bacterial binding and invasion, cause cytotoxicity, and modulate the host immune response. By participating in such diverse aspects of the host-pathogen interaction, OM vesicles are potent bacterial virulence factors. Formation of bacterial OM vesiclesNaturally produced bacterial vesicles are discrete, closed OM blebs produced by growing cells, not products of cell lysis or cell death (Mug-Opstelte...

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“…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

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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.

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Interaction of Actinobacillus actinomycetemcomitans outer membrane vesicles with HL60 cells does not require leukotoxin

Abstract: Summary Outer membrane derived vesicles (MVs) secreted by

Cited by 64 publications

References 56 publications

Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles Are Internalized in Human Host Cells and Trigger NOD1- and NOD2-Dependent NF-κB Activation

Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles Are Internalized in Human Host Cells and Trigger NOD1- and NOD2-Dependent NF-κB Activation

Bacterial outer membrane vesicles and the host–pathogen interaction

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

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