Post-translational modifications in sepsis: Mechanistic insights and therapeutic opportunities

Abstract

Sepsis, a life-threatening condition marked by systemic inflammation and multi-organ dysfunction, poses a persistent clinical challenge. Post-translational modifications (PTMs) dynamically regulated inflammatory signaling, immune responses, and cell death, positioning them as a pivotal focus in sepsis research. This review systematically explores the regulatory networks of five key PTMs - phosphorylation, ubiquitination, SUMOylation, acetylation, and lactylation - in sepsis. In this review, we highlight recent discoveries of genes and molecules that modulate these PTMs, influencing inflammation and organ dysfunction, and evaluate their potential as therapeutic targets or prognostic biomarkers. Furthermore, we discuss how PTMs offer novel therapeutic opportunities, providing novel insights to address the shortcomings of traditional anti-infective approaches.

Keywords

Sepsis / Post-translational modifications / Phosphorylation / Ubiquitination / SUMOylation / Acetylation / Lactylation / Inflammation

Funding

This work was supported by the Beijing Natural Science Foundation (grant number: L246039), the National Natural Science Foundation of China (grant numbers: 82372189, 81871586, and 82172128), and the Beijing High-Level Public Health Technical Talent Training Program (Discipline Backbone Talent 02-32).

Conflict of interest

Liuluan Zhu is the Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.