Emerging views on integrin signaling via Rac1 during invasin-promoted bacterial uptake

Wong, Ka-Wing; Isberg, Ralph R.

doi:10.1016/j.mib.2004.12.009

Cited by 48 publications

(42 citation statements)

References 38 publications

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“…Yersiniae deficient in the secretion of Yops efficiently activated autophagy through the engagement of ␤ 1 integrin receptors and cell invasion. The induction of autophagy involved the Yersinia adhesins invasin and YadA which cluster ␤ 1 integrins to gain access into eukaryotic cells (26,27,58). Many bacteria and viruses stimulate ␤ 1 integrins (75)(76)(77), and this is a first study demonstrating the induction of autophagy as a result of microbial ␤ 1 integrin activation.…”

Section: Discussionmentioning

confidence: 99%

“…The stimulation of ␤ 1 integrins by Yersinia activates several signaling intermediates that could also function in autophagy. Invasin-mediated cell invasion involves the recruitment of focal adhesion complex components that link integrin signaling to actin cytoskeleton reorganization (26,27,54,58,62). Some focal adhesion-related proteins have recently been shown to be important for autophagosome formation.…”

Section: Discussionmentioning

confidence: 99%

“…The Yersinia outer surface protein invasin is central for the pathogenicity of enteropathogenic yersiniae. Invasin clusters and activates eukaryotic ␤ 1 integrin receptors which promotes uptake of the bacteria into the host cell (25)(26)(27). The invasin-mediated internalization process is important for the initial phase of infection, enabling enteropathogenic yersiniae to penetrate the host mucosa and traverse to the underlying lymphoid tissue of the Peyers' patches.…”

Section: ␤ 1 Integrin-dependent Engulfment Of Yersinia Enterocolitica Bymentioning

confidence: 99%

“…Enteropathogenic yersiniae harbor invasin as a prominent outer membrane protein. Invasin mediates adherence to eukaryotic cells by binding to ␤ 1 integrins and thereby promotes bacterial uptake into host cells which is accompanied by a proinflammatory reaction (25)(26)(27)54). We compared the autophagic responses induced by WA-C and the invasin-negative mutant WA-C-⌬inv.…”

Section: Yersinia Invasin Essentially Contributes To the Induction Ofmentioning

confidence: 99%

“…enterocolitica invasin binds and activates eukaryotic cells specifically via ␤ 1 integrin receptors (26,27,54). We attempted to characterize the induction of autophagy by ␤ 1 integrins in response to Yersinia infection in more detail.…”

Section: Yersinia-induced Autophagy Involves Engagement Of ␤ 1 Integrmentioning

confidence: 99%

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β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

Deuretzbacher

Czymmeck

Reimer

et al. 2009

The Journal of Immunology

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Autophagy is a central lysosomal degradation process that is essential for the maintenance of cellular homeostasis. Autophagy has furthermore emerged as integral part of the host immune response. Autophagic processes promote the separation and degradation of intracellular microorganisms which contributes to the development of innate and adaptive immunity. Some pathogenic microbes have therefore evolved mechanisms to evade or impede autophagy. We analyzed the effects of the enteropathogenic bacterium Yersinia enterocolitica on autophagy in macrophages. Yersiniae use a number of defined adhesins and secreted proteins to manipulate host immune responses. Our results showed that Y. enterocolitica defective in type III protein secretion efficiently activated autophagy in macrophages. Autophagy was mediated by the Yersinia adhesins invasin and YadA and particularly depended on the engagement of β1 integrin receptors. Several autophagy-related events followed β1 integrin-mediated engulfment of the bacteria including the formation of autophagosomes, processing of the marker protein LC3, redistribution of GFP-LC3 to bacteria-containing vacuoles, and the segregation of intracellular bacteria by autophagosomal compartments. These results provide direct evidence for the linkage of β1 integrin-mediated phagocytosis and autophagy induction. Multiple microbes signal through integrin receptors, and our results suggest a general principle by which the sensing of an extracellular microbe triggers autophagy. Owing to the importance of autophagy as host defense response, wild-type Y. enterocolitica suppressed autophagy by mobilizing type III protein secretion. The subversion of autophagy may be part of the Y. enterocolitica virulence strategy that supports bacterial survival when β1 integrin-dependent internalization and autophagy activation by macrophages are deleterious for the pathogen.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: ␤ 1 Integrin-dependent Engulfment Of Yersinia Enterocolitica Bymentioning

confidence: 99%

Section: Yersinia Invasin Essentially Contributes To the Induction Ofmentioning

confidence: 99%

Section: Yersinia-induced Autophagy Involves Engagement Of ␤ 1 Integrmentioning

confidence: 99%

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β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

Deuretzbacher

Czymmeck

Reimer

et al. 2009

The Journal of Immunology

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Integrin Trafficking

2008

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Engineering Cyborg Bacteria Through Intracellular Hydrogelation

et al. 2023

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Natural and artificial cells are two common chassis in synthetic biology. Natural cells can perform complex tasks through synthetic genetic constructs, but their autonomous replication often causes safety concerns for biomedical applications. In contrast, artificial cells based on nonreplicating materials, albeit possessing reduced biochemical complexity, provide more defined and controllable functions. Here, for the first time, the authors create hybrid material‐cell entities termed Cyborg Cells. To create Cyborg Cells, a synthetic polymer network is assembled inside each bacterium, rendering them incapable of dividing. Cyborg Cells preserve essential functions, including cellular metabolism, motility, protein synthesis, and compatibility with genetic circuits. Cyborg Cells also acquire new abilities to resist stressors that otherwise kill natural cells. Finally, the authors demonstrate the therapeutic potential by showing invasion into cancer cells. This work establishes a new paradigm in cellular bioengineering by exploiting a combination of intracellular man‐made polymers and their interaction with the protein networks of living cells.

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Emerging views on integrin signaling via Rac1 during invasin-promoted bacterial uptake

Cited by 48 publications

References 38 publications

β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

Integrin Trafficking

Engineering Cyborg Bacteria Through Intracellular Hydrogelation

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