Dysregulation of stress-induced translational control by porphyromonas gingivalis in host cells

KNOWLES, Alex A., CAMPBELL, Susan G., CROSS, Neil A. and STAFFORD, Prachi (2023). Dysregulation of stress-induced translational control by porphyromonas gingivalis in host cells. Microorganisms, 11 (3): 606.

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Abstract

Porphyromonas gingivalis contributes to the chronic oral disease periodontitis, triggering the activation of host inflammatory responses, inducing cellular stresses such as oxidation. During stress, host cells can activate the Integrated Stress Response (ISR), a pathway which determines cellular fate, by either downregulating protein synthesis and initiating a stress–response gene expression program, or by initiating programmed cell death. Recent studies have implicated the ISR within both host antimicrobial defenses and the pathomechanism of certain microbes. In this study, using a combination of immunofluorescence confocal microscopy and immunoblotting, the molecular mechanisms by which P. gingivalis infection alters translation attenuation during oxidative stress-induced activation of the ISR in oral epithelial cells were investigated. P. gingivalis infection alone did not result in ISR activation. In contrast, infection coupled with stress caused differential stress granule formation and composition. Infection heightened stress-induced translational repression independently of core ISR mediators. Heightened translational repression during stress was observed with both P. gingivalis–conditioned media and outer membrane vesicles, implicating a secretory factor in this exacerbated translational repression. The effects of gingipain inhibitors and gingipain-deficient P. gingivalis mutants confirmed these pathogen-specific proteases as the effector of exacerbated translational repression. Gingipains are known to degrade the mammalian target of rapamycin (mTOR) and the findings of this study implicate the gingipain-mTOR axis as the effector of host translational dysregulation during stress.

Item Type:	Article
Uncontrolled Keywords:	3107 Microbiology; 3207 Medical microbiology
Identification Number:	https://doi.org/10.3390/microorganisms11030606
SWORD Depositor:	Symplectic Elements
Depositing User:	Symplectic Elements
Date Deposited:	03 Mar 2023 11:32
Last Modified:	03 Mar 2023 11:32
URI:	https://shura.shu.ac.uk/id/eprint/31606

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