Propionibacterium acnes evades microbicidal phagocytosis by inhibiting the mitochondrial biogenesis of nucleus pulposus cells

TL;DR

This study reveals how Propionibacterium acnes evades destruction by nucleus pulposus cells, leading to chronic intervertebral disc degeneration.

Contribution

The study identifies a novel mechanism by which P. acnes inhibits mitochondrial biogenesis in nucleus pulposus cells to avoid elimination.

Findings

P. acnes inhibits mitochondrial biogenesis in nucleus pulposus cells via the AMPK/SIRT-1/PGC-1α pathway.

Impaired mitochondria fail to produce enough ATP and reactive oxygen species to kill P. acnes.

This evasion mechanism leads to persistent colonization and chronic intervertebral disc degeneration.

Abstract

Although an increasing number of investigators confirm the latent infection of Propionibacterium acnes in degenerated nucleus pulposus tissue, the molecular mechanism by which P. acnes evades being eliminated and establishes persistent colonization in the nucleus pulposus (NP) tissue remains unknown. In this study, we ascertained that despite the resistance by nucleus pulposus cells (NPCs) to the invasion of P. acnes through microbicidal phagocytosis, P. acnes is able to nevertheless promote its long‐term colonization by inhibiting the sustained bactericidal capability of NPCs. This allows P. acnes to reside in intervertebral discs for an extended period, ultimately inducing chronic infectious intervertebral disc degeneration (IVDD). Mechanistically, P. acnes impairs the mitochondrial biogenesis of NPCs through the AMPK/SIRT‐1/PGC‐1α signaling pathway. This results in impaired mitochondria that are unable to generate sufficient ATP and deliver mitochondrial reactive oxygen species (mROS) to carry out the bactericidal process effectively, thus hampering the sustained microbicidal function. These findings provide novel insights into how P. acnes evades being phagocytosed and killed by NPCs and may offer potential therapeutic targets for the treatment of infectious IVDD.

P. acnes infection impairs the mitochondrial biogenesis of nucleus pulposus cells (NPCs) through the AMPK/SIRT‐1/PGC‐1α signaling pathway. This results in impaired mitochondria that are unable to generate sufficient ATP, and impaired delivery of mitochondrial reactive oxygen species to carry out the bactericidal process effectively. Consequently, this compromises sustained microbicidal function, ultimately inducing chronic infectious intervertebral disc degeneration.

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