Human α- and β-Defensins Bind to Immobilized Adhesins from<i>Porphyromonas gingivalis</i>

Dietrich, Deborah E.; Xiao, Xiangjun; Dawson, Deborah V.; Bélanger, Myriam; Xie, Hua; Progulske‐Fox, Ann; Brogden, Kim A.

doi:10.1128/iai.00997-08

Cited by 23 publications

(24 citation statements)

References 63 publications

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“…A major anti-microbial mechanism of defensins is manifested via their direct interaction with the bacterial membrane, leading to its disorganization and compromised integrity [38]. Another major mechanism of the anti-microbial activity of defensins involves interaction with bacterial proteins, either cell-associated (e.g., secretion portals [39,40], fimbrial adhesins [41]) or secreted (e.g., toxins [34,35,42,43]). It is easy to recognize that both anti-microbial mechanisms are important and complementary.…”

Section: Discussionmentioning

confidence: 99%

Retrocyclins neutralize bacterial toxins by potentiating their unfolding

Kudryashova

Seveau

et al. 2015

Biochemical Journal

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Defensins are a class of immune peptides with a broad range of activities against bacterial, fungal and viral pathogens. Besides exerting direct anti-microbial activity via dis-organization of bacterial membranes, defensins are also able to neutralize various unrelated bacterial toxins. Recently, we have demonstrated that in the case of human α- and β-defensins, this later ability is achieved through exploiting toxins’ marginal thermodynamic stability, i.e. defensins act as molecular anti-chaperones unfolding toxin molecules and exposing their hydrophobic regions and thus promoting toxin precipitation and inactivation [Kudryashova et al. (2014) Immunity 41, 709–721]. Retrocyclins (RCs) are humanized synthetic θ-defensin peptides that possess unique cyclic structure, differentiating them from α- and β-defensins. Importantly, RCs are more potent against some bacterial and viral pathogens and more stable than their linear counterparts. However, the mechanism of bacterial toxin inactivation by RCs is not known. In the present study, we demonstrate that RCs facilitate unfolding of bacterial toxins. Using differential scanning fluorimetry (DSF), limited proteolysis and collisional quenching of internal tryptophan fluorescence, we show that hydrophobic regions of toxins normally buried in the molecule interior become more exposed to solvents and accessible to proteolytic cleavage in the presence of RCs. The RC-induced unfolding of toxins led to their precipitation and abrogated activity. Toxin inactivation by RCs was strongly diminished under reducing conditions, but preserved at physiological salt and serum concentrations. Therefore, despite significant structural diversity, α-, β- and θ-defensins employ similar mechanisms of toxin inactivation, which may be shared by anti-microbial peptides from other families.

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Section: Discussionmentioning

confidence: 99%

Retrocyclins neutralize bacterial toxins by potentiating their unfolding

Kudryashova

Seveau

et al. 2015

Biochemical Journal

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“…For instance, the human beta-defensin 3 has been shown to bind Bla g 2 and could modify the ability of Bla g 2 to induce localized allergic inflammatory and mucosal responses (44, 45). Bla g 7 can potently induce T cell immunoglobulin mucin domain (TIM) 4 expression on dendritic cells (46), which plays a critical role in T cell proliferation and Th2 cell development (47, 48). Per a 7 has been demonstrated to up-regulate the expression of protease-activated receptors, thereby, triggering Th2 cytokines secretion (e.g., IL-4 and IL-13) (49).…”

Section: Introductionmentioning

confidence: 99%

Cockroach allergen exposure and risk of asthma

Danh

Zhao

Gao

2016

Allergy

122

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Cockroach sensitization is an important risk factor for the development of asthma. However, its underlying immune mechanisms and the genetic etiology for differences in allergic responses remain unclear. Cockroach allergens identification and their expression as biologically active recombinant proteins has provided a basis for studying the mechanisms regarding cockroach allergens induced allergic sensitization and asthma. Glycans in allergens may play a crucial role in the immunogenicity of allergic diseases. Protease-activated receptor (PAR)-2, Toll-like receptor (TLR), and C-type lectin receptors have been suggested to be important for the penetration of cockroach allergens through epithelial cells to mediate allergen uptake, dendritic cell maturation, antigen presenting cell (APC) function in T cell polarization, and cytokine production. Environmental pollutants, which often co-exist with the allergen, could synergistically elicit allergic inflammation, and aryl hydrocarbon receptor (AhR) activation and signaling may serve as a link between these two elements. Genetic factors may also play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and asthma-related phenotypes. In this review, we will discuss the epidemiological evidence for cockroach allergen-induced asthma, cockroach allergens, the mechanisms regarding cockroach allergens induced innate immune responses, and the genetic basis for cockroach sensitization.

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“…Previous studies suggest that further prophylactic and therapeutic approaches against periodontal diseases associated with P. gingivalis could be developed based on hemagglutinins. For example, human alpha- and beta- defensins were shown to bind P. gingivalis rHagB and enhance the IgG response in mice which could potentially lead to P. gingivalis clearance from the host [58–59]. HagA has been recognized by serum from a periodontal patient while we have previously reported that HagA expression in a S. enterica serovar Enterica vaccine strain was able to induce a humoral immune response against this hemagglutinin [40].…”

Section: Discussionmentioning

confidence: 99%

Both the unique and repeat regions of the Porphyromonas gingivalis hemagglutin A are involved in adhesion and invasion of host cells

et al. 2012

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Porphyromonas gingivalis is one of the major etiologic agents of adult periodontitis and has been associated with cardiovascular diseases. It expresses multiple hemagglutinins that are significant virulence factors that play an important role in bacterial attachment and invasion of host cells. The objective of this study was to determine the impact of P. gingivalis hemagglutinin A (HagA) on the attachment to and invasion of human coronary artery endothelial cells (HCAEC) and gingival epithelial cells (GEC). Bacterial strains expressing the HagA protein (or subunits), including Escherichia coli carrying plasmid pEKS5, E. coli carrying plasmid ST2, and Salmonella enterica serovar Typhimurium with plasmid pNM1.1 were used in this study. The strains were tested for their ability to attach to and invade HCAEC and GEC using antibiotic protection assays. In addition, the unique 5′ N-terminal non-repeated segment of HagA was purified in recombinant form and a monoclonal antibody was created against the polypeptide. The monoclonal antibody against the unique portion of HagA was tested for inhibitory activity in these assays. The attachment of both E. coli strains expressing HagA fragment to host cells was significantly increased compared to their respective controls. However they did not invade GEC or HCAEC. Interestingly, HagA expression in the Salmonella strain increased both adherence to and invasion of HCAEC, which may be due to the presence of the entire hagA ORF. A monoclonal antibody against the unique 5′ N-terminal portion of HagA reduced invasion. Further experiments are needed to determine the role of the unique and the repeat segments of P. gingivalis HagA.

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Human α- and β-Defensins Bind to Immobilized Adhesins fromPorphyromonas gingivalis

Cited by 23 publications

References 63 publications

Retrocyclins neutralize bacterial toxins by potentiating their unfolding

Retrocyclins neutralize bacterial toxins by potentiating their unfolding

Cockroach allergen exposure and risk of asthma

Both the unique and repeat regions of the Porphyromonas gingivalis hemagglutin A are involved in adhesion and invasion of host cells

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