The Commonalities in Bacterial Effector Inhibition of Apoptosis

Robinson, Keith S.; Aw, Rochelle

doi:10.1016/j.tim.2016.04.002

Cited by 29 publications

(21 citation statements)

References 81 publications

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“…Based on these sets of data, we proposed that Mtb can activate the canonical intrinsic apoptotic pathway in a process that involves EsxA and DIM. In recent years, it has become widely accepted that translocated bacterial effectors can target specific points in apoptotic‐related pathways (Robinson & Aw, ). Mtb produces several pro‐apoptotic proteins such as EsxA, the 19 kDa lipoprotein (Ciaramella, Martino, Cicconi, Colizzi, & Fraziano, ) and HBHA (Choi et al, ).…”

Section: Discussionmentioning

confidence: 99%

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ESX-1 and phthiocerol dimycocerosates ofMycobacterium tuberculosisact in concert to cause phagosomal rupture and host cell apoptosis

Augenstreich

Arbués

Siméone

et al. 2017

Cellular Microbiology

194

226

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Although phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, little is known about their mechanism of action. Localized in the outer membrane of mycobacterial pathogens, DIM are predicted to interact with host cell membranes. Interaction with eukaryotic membranes is a property shared with another virulence factor of Mtb, the early secretory antigenic target EsxA (also known as ESAT-6). This small protein, which is secreted by the type VII secretion system ESX-1 (T7SS/ESX-1), is involved in phagosomal rupture and cell death induced by virulent mycobacteria inside host phagocytes. In this work, by the use of several knock-out or knock-in mutants of Mtb or Mycobacterium bovis BCG strains and different cell biological assays, we present conclusive evidence that ESX-1 and DIM act in concert to induce phagosomal membrane damage and rupture in infected macrophages, ultimately leading to host cell apoptosis. These results identify an as yet unknown function for DIM in the infection process and open up a new research field for the study of the interaction of lipid and protein virulence factors of Mtb.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ESX-1 and phthiocerol dimycocerosates ofMycobacterium tuberculosisact in concert to cause phagosomal rupture and host cell apoptosis

Augenstreich

Arbués

Siméone

et al. 2017

Cellular Microbiology

194

226

View full text Add to dashboard Cite

show abstract

“…If these bodies are not cleared, they will undergo secondary necrosis (rupture), releasing cytosolic damage-associated molecular patterns (DAMPs) to the extracellular space 80 . The role of apoptosis against infection is perhaps best appreciated by inference, since numerous viruses and bacteria encode apoptosis inhibitors that are essential for virulence (reviewed in 81,82 ). This again raises the conundrums posed in the Red Pawn Hypothesis, if most viruses evade apoptosis, are there pathogens that apoptosis effectively counters, providing fully penetrant innate immunity (Box 1).…”

Section: Apoptosis During Infectionsmentioning

confidence: 99%

Programmed cell death as a defence against infection

Rayamajhi²,

2017

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Eukaryotic cells can die from physical trauma, resulting in necrosis. Alternately, they can die via programmed cell death upon stimulation of specific signalling pathways. Here we discuss the utility of four cell death pathways in innate immune defence against bacterial and viral infection: apoptosis, necroptosis, pyroptosis and NETosis. We describe the interactions that interweave different programmed cell death pathways, which create complex signalling networks that cross-guard each other in the evolutionary arms race with pathogens. Finally, we describe how the resulting cell corpses — apoptotic bodies, pore-induced intracellular traps (PITs) and neutrophil extracellular traps (NETs) — promote clearance of infection.

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“…86 The role of caspase-7 in inflammasome-associated apoptosis needs to be investigated further under various experimental settings because L. pneumophila and other intracellular parasitic pathogens have the potential to inhibit apoptosis in host cells. 87 Although caspase-8 has been suggested to process GSDMD into GSDMD p30, inflammasome-induced caspase-8 activation leads to apoptosis, not pyroptosis. This may be because caspase-8 is less efficient than caspase-1 at cleaving GSDMD and induces the activation of caspase-3, which inactivates GSDMD.…”

Section: Asc-dependent Caspase-8 Activationmentioning

confidence: 99%