Integrin-mediated internalization of Staphylococcus aureus does not require vinculin

Borisova, Marina; Shi, Yong; Buntru, Alexander; Wörner, Susanne; Ziegler, Wolfgang; Hauck, Christof R.

doi:10.1186/1471-2121-14-2

Cited by 8 publications

(9 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, various lines of evidence have demonstrated that the excessive activation of TGF‐β is associated with various disorders. On the other hand, it is well accepted that some bacteria utilize integrin cascade to invade into the cells (Pizarro‐Cerda and Cossart, ; Kim et al ., 2009; Borisova et al ., ). Based on our idea in the present study, these facts may suggest that bacteria or virulence factors that are capable of inducing actin rearrangements via integrin cascade promote the activation of TGF‐β from the ECM, leading to TGF‐β‐related diseases.…”

Section: Discussionmentioning

confidence: 97%

Aggregatibacter actinomycetemcomitansouter membrane protein 29 (Omp29) induces TGF-β-regulated apoptosis signal in human gingival epithelial cells via fibronectin/integrinβ1/FAK cascade

Yoshimoto

Fujita

Kajiya

et al. 2016

Cellular Microbiology

View full text Add to dashboard Cite

Gingival junctional epithelial cell apoptosis caused by periodontopathic bacteria exacerbates periodontitis. This pathological apoptosis is involved in the activation of transforming growth factor β (TGF-β). However, the molecular mechanisms by which microbes induce the activation of TGF-β remain unclear. We previously reported that Aggregatibacter actinomycetemcomitans (Aa) activated TGF-β receptor (TGF-βR)/smad2 signalling to induce epithelial cell apoptosis, even though Aa cannot bind to TGF-βR. Additionally, outer membrane protein 29 kDa (Omp29), a member of the Aa Omps family, can induce actin rearrangements via focal adhesion kinase (FAK) signalling, which also plays a role in the activation of TGF-β by cooperating with integrin. Accordingly, we hypothesized that Omp29-induced actin rearrangements via FAK activity would enhance the activation of TGF-β, leading to gingival epithelial cell apoptosis in vitro. By using human gingival epithelial cell line OBA9, we found that Omp29 activated TGF-βR/smad2 signalling and decreased active TGF-β protein levels in the extracellular matrix (ECM) of cell culture, suggesting the transactivation of TGF-βR. Inhibition of actin rearrangements by cytochalasin D or blebbistatin and knockdown of FAK or integrinβ1 expression by siRNA transfection attenuated TGF-βR/smad2 signalling activity and reduction of TGF-β levels in the ECM caused by Omp29. Furthermore, Omp29 bound to fibronectin (Fn) to induce its aggregation on integrinβ1, which is associated with TGF-β signalling activity. All the chemical inhibitors and siRNAs tested blocked Omp29-induced OBA9 cells apoptosis. These results suggest that Omp29 binds to Fn in order to facilitate Fn/integrinβ1/FAK signalling-dependent TGF-β release from the ECM, thereby inducing gingival epithelial cell apoptosis via TGF-βR/smad2 pathway.

show abstract

Section: Discussionmentioning

confidence: 97%

Aggregatibacter actinomycetemcomitansouter membrane protein 29 (Omp29) induces TGF-β-regulated apoptosis signal in human gingival epithelial cells via fibronectin/integrinβ1/FAK cascade

Yoshimoto

Fujita

Kajiya

et al. 2016

Cellular Microbiology

View full text Add to dashboard Cite

show abstract

“…Upon phosphorylation by integrins, Src associates and activates FAK to regulate several actin-related processes, including phosphorylation of key substrates such as paxillin and cortactin 32 51 52 53 54 55 . It has also been shown that activation of host cell Src and FAK is correlated to the actin dependent internalization of bacterial pathogens 56 57 58 59 . The serine-threonine kinase, PAK, acts as an effector of Rac1 and other GTPases 60 61 and previous results from the author’s group demonstrate that cells expressing constitutively active Rac1 are more susceptible to EAs invasion 62 .…”

Section: Discussionmentioning

confidence: 99%

Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling

Ferreira

Horjales²,

Bonfim-Melo

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Mevalonate kinase (MVK) is an essential enzyme acting in early steps of sterol isoprenoids biosynthesis, such as cholesterol in humans or ergosterol in trypanosomatids. MVK is conserved from bacteria to mammals, and localizes to glycosomes in trypanosomatids. During the course of T. cruzi MVK characterization, we found that, in addition to glycosomes, this enzyme may be secreted and modulate cell invasion. To evaluate the role of TcMVK in parasite-host cell interactions, TcMVK recombinant protein was produced and anti-TcMVK antibodies were raised in mice. TcMVK protein was detected in the supernatant of cultures of metacyclic trypomastigotes (MTs) and extracellular amastigotes (EAs) by Western blot analysis, confirming its secretion into extracellular medium. Recombinant TcMVK bound in a non-saturable dose-dependent manner to HeLa cells and positively modulated internalization of T. cruzi EAs but inhibited invasion by MTs. In HeLa cells, TcMVK induced phosphorylation of MAPK pathway components and proteins related to actin cytoskeleton modifications. We hypothesized that TcMVK is a bifunctional enzyme that in addition to playing a classical role in isoprenoid synthesis in glycosomes, it is secreted and may modulate host cell signaling required for T. cruzi invasion.

show abstract

“…The contribution to S. aureus invasion of different integrin‐interacting proteins appears to differ in various cell types. For example, whereas focal adhesion kinase is essential for S. aureus invasion of fibroblasts, vinculin is dispensable (38, 39). Our data now establish that ILK is an indispensable component for staphylococcal internalization in epidermal keratinocytes and that it does not appreciably mediate at least a subset of TLR2‐mediated innate immunity responses to microbial pathogens.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus keratinocyte invasion is mediated by integrin‐linked kinase and Rac1

Sayedyahossein

Rudkouskaya

et al. 2014

FASEB j.

View full text Add to dashboard Cite

Staphylococcus aureus is a major component of the skin microbiota and causes a large number of serious infections. S. aureus first interacts with epidermal keratinocytes to breach the epidermal barrier through mechanisms not fully understood. By use of primary keratinocytes from mice with epidermis-restricted Ilk gene inactivation and control integrin-linked kinase (ILK)-expressing littermates, we investigated the role of ILK in epidermal S. aureus invasion. Heat-killed, but not live, bacteria were internalized to Rab5-and Rab7-positive phagosomes, and incubation with keratinocyte growth factor increased their uptake 2.5-fold. ILK-deficient mouse keratinocytes internalized bacteria 2-to 4-fold less efficiently than normal cells. The reduced invasion by live S. aureus of ILK-deficient cells was restored in the presence of exogenous, constitutively active Rac1. Thus, Rac1 functions downstream from ILK during invasion. Further, invasion by S. aureus of Rac1-deficient cells was 2.5-fold lower than in normal cells. Paradoxically, staphylococcal cutaneous penetration of mouse skin explants with ILK-deficient epidermis was 35-fold higher than that of normal skin, indicating defects in epidermal barrier function in the absence of ILK. Thus, we identified an ILK-Rac1 pathway essential for bacterial invasion of keratinocytes, and established ILK as a key contributor to prevent invasive staphylococcal cutaneous infection.-Sayedyahossein, S., Xu, S. X., Rudkouskaya, A., McGavin, M. J., McCormick, J. K., Dagnino, L. Staphylococcus aureus keratinocyte invasion is mediated by integrinlinked kinase and Rac1. FASEB J. 29, 711-723 (2015). www.fasebj.org

show abstract

Integrin-mediated internalization of Staphylococcus aureus does not require vinculin

Cited by 8 publications

References 52 publications

Aggregatibacter actinomycetemcomitansouter membrane protein 29 (Omp29) induces TGF-β-regulated apoptosis signal in human gingival epithelial cells via fibronectin/integrinβ1/FAK cascade

Aggregatibacter actinomycetemcomitansouter membrane protein 29 (Omp29) induces TGF-β-regulated apoptosis signal in human gingival epithelial cells via fibronectin/integrinβ1/FAK cascade

Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling

Staphylococcus aureus keratinocyte invasion is mediated by integrin‐linked kinase and Rac1

Contact Info

Product

Resources

About