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Microbes & Immunity

REVIEW ARTICLE
Post-translational modifications in sepsis:

Mechanistic insights and therapeutic
opportunities

Wenyue Gao 1,2,3,4 , Yue Zhang 1,2,3 , and Liuluan Zhu 1,2,3 *

1 Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing
Ditan Hospital, Capital Medical University, Beijing, China
2 Beijing Institute of Infectious Diseases, Beijing, China
3 National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing,
China
4 Department of Infectious, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning,
China

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
*Corresponding author:
Liuluan Zhu targets or prognostic biomarkers. Furthermore, we discuss how PTMs offer novel
(zhuliuluan@ccmu.edu.cn) therapeutic opportunities, providing novel insights to address the shortcomings of
Citation: Gao W, Zhang Y, Zhu L. traditional anti-infective approaches.
Post-translational modifications in
sepsis: Mechanistic insights and
therapeutic opportunities. Microbes Keywords: Sepsis; Post-translational modifications; Phosphorylation; Ubiquitination;
& Immunity. 2025;2(3):1-14. SUMOylation; Acetylation; Lactylation; Inflammation
doi: 10.36922/MI025090016
Received: February 28, 2025
Revised: April 11, 2025
1. Introduction
Accepted: April 14, 2025
Sepsis arises from a dysregulated host response to infection, resulting in systemic
Published online: April 24, 2025
inflammation and multiple organ dysfunctions. Complications such as acute kidney
1
Copyright: © 2025 Author(s). injury (AKI), acute lung injury (ALI), and myocardial injury are frequent and severe,
This is an Open-Access article contributing to elevated morbidity and mortality rates. Despite progress in anti-
2-4
distributed under the terms of the
Creative Commons Attribution infective therapies and organ support, the intricate pathogenesis of sepsis continues to
License, permitting distribution, hinder effective clinical management.
and reproduction in any medium,
provided the original work is In eukaryotes, protein function is diversified through post-translational modifications
properly cited. (PTMs), which dynamically regulate cellular processes. Increasingly, PTMs have
5
Publisher’s Note: AccScience been recognized as central regulators of sepsis progression, modulating inflammatory
Publishing remains neutral with signaling, immune cell polarization, and programmed cell death. This review examines
6
regard to jurisdictional claims in
published maps and institutional five major PTMs – phosphorylation, ubiquitination, SUMOylation, acetylation, and
affiliations. lactylation, an emerging form of modification – focusing on their roles in sepsis, and
Volume 2 Issue 3 (2025) 1 doi: 10.36922/MI025090016