Role for Telomerase in Listeria monocytogenes Infection

Samba-Louaka, Ascel; Stavru, Fabrizia; Cossart, Pascale

doi:10.1128/iai.00614-12

Cited by 17 publications

(12 citation statements)

References 51 publications

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“…LLO-induced degradation of Mff appeared proteasome independent, because it was not prevented by treatment with MG132 and lactacystin (Fig. S2E), consistent with previous reports suggesting that LLO induces protein degradation through an as-yet-unknown pathway (28,29). Timelapse studies of Mff-GFP in HeLa cells treated with LLO indicate that Mff degradation begins almost immediately after LLO addition ( Fig.…”

Section: Resultssupporting

confidence: 90%

Atypical mitochondrial fission upon bacterial infection

Stavru

Palmer

Wang

et al. 2013

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

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111

110

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We recently showed that infection by Listeria monocytogenes causes mitochondrial network fragmentation through the secreted pore-forming toxin listeriolysin O (LLO). Here, we examine factors involved in canonical fusion and fission. Strikingly, LLOinduced mitochondrial fragmentation does not require the traditional fission machinery, as Drp1 oligomers are absent from fragmented mitochondria following Listeria infection or LLO treatment, as the dynamin-like protein 1 (Drp1) receptor Mff is rapidly degraded, and as fragmentation proceeds efficiently in cells with impaired Drp1 function. LLO does not cause processing of the fusion protein optic atrophy protein 1 (Opa1), despite inducing a decrease in the mitochondrial membrane potential, suggesting a unique Drp1-and Opa1-independent fission mechanism distinct from that triggered by uncouplers or the apoptosis inducer staurosporine. We show that the ER marks LLO-induced mitochondrial fragmentation sites even in the absence of functional Drp1, demonstrating that the ER activity in regulating mitochondrial fission can be induced by exogenous agents and that the ER appears to regulate fission by a mechanism independent of the canonical mitochondrial fission machinery.mitochondrial dynamics | live cell imaging | actin M itochondria are essential organelles that perform a multitude of functions, ranging from the production of biosynthetic intermediates and energy to innate immune signaling and cellular calcium buffering or the storage of proapoptotic components (1). To perform these diverse functions, mitochondria respond to cellular cues and display a highly variable and dynamic morphology, constantly undergoing fusion and fission. It is becoming increasingly clear that mitochondrial dynamics and function are deeply interconnected, and mitochondrial dysfunction is associated with a range of diseases.Wild-type mitochondrial morphology and function are maintained by a balance between mitochondrial fusion and fission.

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Section: Resultssupporting

confidence: 90%

Atypical mitochondrial fission upon bacterial infection

Stavru

Palmer

Wang

et al. 2013

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

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111

110

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“…Since then, LLO has been shown to have many different extracellular activities on the host cell [19] . Remarkably, the pore formation of LLO has been shown to lead to degradation of at least 2 other proteins during infection, the catalytic subunit of the human telomerase complex (hTERT), and the human E2 SUMO enzyme Ubc9 [20] , [41] . Although the mechanism by which hTERT levels were decreased remains to be determined, the degradation of Ubc9 was shown to be partially dependent on an aspartyl-protease.…”

Section: Discussionmentioning

confidence: 99%

“…There, Listeria overexpresses ActA, which allows escape from autophagy and also polymerizes host actin, in order to move and spread to the neighboring cells [18] . Importantly, in addition to mediating vacuole escape, LLO also targets several host functions such as, host gene transcription, mitochondrial dynamics, host protein synthesis or SUMOylation [19] , [20] . Thus, L. monocytogenes has evolved many mechanisms to manipulate the host to its advantage.…”

Section: Introductionmentioning

confidence: 99%

Listeria monocytogenes Dampens the DNA Damage Response

et al. 2014

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The DNA damage response (DDR) is an essential signaling pathway that detects DNA lesions, which constantly occur upon either endogenous or exogenous assaults, and maintains genetic integrity. An infection by an invading pathogen is one such assault, but how bacteria impact the cellular DDR is poorly documented. Here, we report that infection with Listeria monocytogenes induces host DNA breaks. Strikingly, the signature response to these breaks is only moderately activated. We uncover the role of the listerial toxin listeriolysin O (LLO) in blocking the signaling response to DNA breaks through degradation of the sensor Mre11. Knocking out or inactivating proteins involved in the DDR promotes bacterial replication showing the importance of this mechanism for the control of infection. Together, our data highlight that bacterial dampening of the DDR is critical for a successful listerial infection.

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“…Recent data suggest that LLO stimulates degradation of human telomerase reverse transcriptase [77], although that regulation is due in part to Ca 2+ flux as a result of membrane perturbation. Taken together, these data suggest that CDCs can have profound influence on transcriptional regulation of the intoxicated cell, which would likely affect the outcome of infection.…”

Section: Intracellular Effects Of Cdc Intoxicationmentioning

confidence: 99%

More Than a Pore: The Cellular Response to Cholesterol-Dependent Cytolysins

Cassidy

O’Riordan

2013

Toxins

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Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC) are a family of pore-forming toxins expressed predominately by Gram-positive bacterial pathogens. The structure and assembly of some of these oligomeric toxins on the host membrane have been described, but how the targeted cell responds to intoxication by the CDCs is not as clearly understood. Many CDCs induce lysis of their target cell and can activate apoptotic cascades to promote cell death. However, the extent to which intoxication causes cell death is both CDC- and host cell-dependent, and at lower concentrations of toxin, survival of intoxicated host cells is well documented. Additionally, the effect of CDCs can be seen beyond the plasma membrane, and it is becoming increasingly clear that these toxins are potent regulators of signaling and immunity, beyond their role in intoxication. In this review, we discuss the cellular response to CDC intoxication with emphasis on the effects of pore formation on the host cell plasma membrane and subcellular organelles and whether subsequent cellular responses contribute to the survival of the affected cell.

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Role for Telomerase in Listeria monocytogenes Infection

Cited by 17 publications

References 51 publications

Atypical mitochondrial fission upon bacterial infection

Atypical mitochondrial fission upon bacterial infection

Listeria monocytogenes Dampens the DNA Damage Response

More Than a Pore: The Cellular Response to Cholesterol-Dependent Cytolysins

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