Outer membrane protein 100, a versatile virulence factor of <i>Actinobacillus actinomycetemcomitans</i>

Asakawa, Ryuji; Komatsuzawa, Hitoshi; Kawai, Toshihisa; Yamada, Sakuo; Gonçalves, Reginaldo Bruno; Izumi, Shin-ichi; Fujiwara, Takanori; Nakano, Yoshio; Suzuki, Nao; Uchida, Yuushi; Ouhara, Kazuhisa; Shiba, Hideki; Taubman, Martin A.; Kurihara, Hidemi; Sugai, Motoyuki

doi:10.1046/j.1365-2958.2003.03748.x

Cited by 121 publications

(140 citation statements)

References 50 publications

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“…Similar to YadA function in Yersinia, ApiA stimulates A. actinomycetemcomitans autoaggregation, assists translocation into host cells, and binds the human serum protein factor H (26,27). Binding factor H inhibits serum complement activity and protects A. actinomycetemcomitans from killing by the alternative complement pathway (26). Although similar in function, yadA and its homologues in other organisms have not been shown to be induced by H 2 O 2 at this time.…”

Section: Resultsmentioning

confidence: 84%

“…More intriguing was the finding that A. actinomycetemcomitans also induces the outer membrane protein ApiA during coculture. Because ApiA provides protection from killing by the alternative complement component of innate immunity (26), our data represent a demonstration of a metabolic cue produced by one bacterium mediating enhanced resistance to a component of host innate immunity by another. It should be noted that the mechanism of complement inhibition, namely, enhanced binding of the serum protein factor H (Fig.…”

Section: Discussionmentioning

confidence: 84%

“…ApiA is a 33-kDa trimeric outer membrane protein (also referred to as Omp100) (24) that is 55% identical [using pairwise (p) BLAST] to the nonfimbrial adhesin protein YadA in Yersinia pestis and Yersinia enterolitica (25). Similar to YadA function in Yersinia, ApiA stimulates A. actinomycetemcomitans autoaggregation, assists translocation into host cells, and binds the human serum protein factor H (26,27). Binding factor H inhibits serum complement activity and protects A. actinomycetemcomitans from killing by the alternative complement pathway (26).…”

Section: Resultsmentioning

confidence: 99%

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Polymicrobial interactions stimulate resistance to host innate immunity through metabolite perception

Ramsey

Whiteley

2009

Proc. Natl. Acad. Sci. U.S.A.

155

161

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Bacteria in the human oral cavity often grow in an attached multispecies biofilm community. Members of this community display defined interactions that have an impact on the physiology of the individual and the group. Here, we show that during coculture growth with streptococci, the oral pathogen Aggregatibacter actinomycetemcomitans displays enhanced resistance to killing by host innate immunity. The mechanism of resistance involves sensing of the streptococcal metabolite hydrogen peroxide by A. actinomycetemcomitans, which stimulates a genetic program resulting in enhanced expression of the complement resistance protein ApiA. The oxidative stress response regulator OxyR mediates induction of apiA transcription, and this induction is required for coculture resistance to killing by human serum. These findings provide evidence that interaction between community members mediates prokaryotic resistance to host innate immunity and reinforce the need to understand how polymicrobial growth affects interaction with the host immune system.Aggregatibacter ͉ ApiA ͉ complement ͉ peroxide ͉ Streptococcus gordonii

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Section: Resultsmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

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Polymicrobial interactions stimulate resistance to host innate immunity through metabolite perception

Ramsey

Whiteley

2009

Proc. Natl. Acad. Sci. U.S.A.

155

161

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“…Among Gram-negative pathogens, the recruitment of fH as a mechanism of defense against complement attack has been demonstrated for the pathogenic species of Neisseria (24), Haemophilus influenzae (25), Pseudomonas aeruginosa (26), Actinobacillus actinomycetocomitans (27), and Yersinia enterocolitica (28). In the case of Y. enterocolitica, both the YadA and Ail proteins were shown to be receptors for fH (28).…”

Section: Rck Is An Fh-binding Proteinmentioning

confidence: 99%

Human Complement Factor H Binds to Outer Membrane Protein Rck of Salmonella

Jarva

Meri

2010

The Journal of Immunology

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Serum resistance, or resistance to complement-mediated killing, is a key virulence property of microbial pathogens. Rck is a 17-kDa outer membrane protein encoded on the virulence plasmid of Salmonella enterica serovars Typhimurium and Enteritidis. When expressed in either Escherichia coli or S. enterica Typhimurium, Rck confers serum resistance independent of LPS length. Recently, the Rck homolog from Yersinia enterocolitica, Ail, has been shown to bind the complement regulatory protein factor H (fH). Based on these observations, we hypothesized that Rck may also possess this ability. Using both flow cytometery and direct binding analysis, we demonstrate that Rck expressed in E. coli binds fH. We observed fH binding to Rck from human serum and also using the purified protein. Expression of Rck protected bacteria from alternative pathway-mediated killing and was associated with a reduction in C3b, Bb, and membrane attack complex deposition. fH bound to Rck promoted C3b cleavage in the presence of factor I. Binding was specific and mediated by two regions in fH, the short consensus repeats 5–7 and 19 to 20. These results suggest that fH recruitment by Rck is functional and can protect a normally serum-sensitive heterologous host against complement attack. Binding and exploitation of fH may thus contribute to Rck-mediated serum resistance.

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“…More knowledge is available for other AaOMPs (e.g. a 100-kDa OMP), which promotes adherence and invasion to human cells, and induction of IL-1b and TNF-a production by mouse macrophages [18]. Furthermore, a 29-kDa AaOMP is involved in bacterial internalization in gingival epithelial cells [17], and the 12-kDa OapB most likely inhibits the host defence enzyme lysozyme [14,19].…”

Section: Introductionmentioning

confidence: 99%

Peptidoglycan-associated lipoprotein ofAggregatibacter actinomycetemcomitansinduces apoptosis and production of proinflammatory cytokines via TLR2 in murine macrophages RAW 264.7in vitro

Ihalin

Eneslätt

Asikainen

2018

Journal of Oral Microbiology

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Peptidoglycan-associated lipoprotein (PAL) is a conserved pro-inflammatory outer membrane lipoprotein in Gram-negative bacteria. Compared to systemic pathogens, little is known about the virulence properties of PAL in Aggregatibacter actinomycetemcomitans (AaPAL). The aims of this study were to investigate the cytolethality of AaPAL and its ability to induce pro-inflammatory cytokine production in macrophages. Mouse macrophages were stimulated with AaPAL, and the production of IL-1β, IL-6, TNF-α, and MCP-1 was measured after 6, 24, and 48 h. To investigate which receptor AaPAL employs for its interaction with macrophages, anti-toll-like receptor (TLR)2 and anti-TLR4 antibodies were used to block respective TLRs on macrophages. Metabolic activity and apoptosis of the macrophages were investigated after stimulation with AaPAL. AaPAL induced the production of MCP-1, TNF-α, IL-6, and IL-1β from mouse macrophages in order of decreasing abundance. The pre-treatment of macrophages with an anti-TLR2 antibody significantly diminished cytokine production. Under AaPAL stimulation, the metabolic activity of macrophages decreased in a dose- and time-dependent manner. Furthermore, AaPAL induced apoptosis in 56% of macrophages after 48 h of incubation. Our data suggest that AaPAL can kill macrophages by apoptosis. The results also emphasize the role of AaPAL as a potent pro-inflammatory agent in A. actinomycetemcomitans-associated infections.

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Outer membrane protein 100, a versatile virulence factor of Actinobacillus actinomycetemcomitans

Cited by 121 publications

References 50 publications

Polymicrobial interactions stimulate resistance to host innate immunity through metabolite perception

Polymicrobial interactions stimulate resistance to host innate immunity through metabolite perception

Human Complement Factor H Binds to Outer Membrane Protein Rck of Salmonella

Peptidoglycan-associated lipoprotein ofAggregatibacter actinomycetemcomitansinduces apoptosis and production of proinflammatory cytokines via TLR2 in murine macrophages RAW 264.7in vitro

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