Protein post-translational modifications in sepsis: Molecular mechanisms and biomarkers

Sepsis is a common and highly fatal condition in intensive care units and is one of the leading causes of death worldwide. As a clinically complex syndrome with intricate pathophysiology, early identification and assessment of sepsis remain challenging. Deeper insights at the molecular level are crucial for understanding the complex pathophysiological mechanisms, discovering new biomarkers, and improving prognosis. Post-translational modifications (PTMs) refer to the attachment of specific chemical groups to amino acid side chains through covalent, enzymatic, or non-enzymatic means, greatly expanding protein diversity and playing critical roles in many cellular signaling pathways. Here, we elucidate the regulatory roles of PTMs in sepsis pathways and key proteins, including immune response, late-stage inflammatory mediators, cellular metabolic reprogramming, and endothelial injury. We also summarize the progress in research on PTM-related sepsis biomarkers, covering diagnosis, prognosis, and organ dysfunction assessment, with a particular focus on the potential of glycosylation as a biomarker. Furthermore, we review current methodologies for studying PTMs. Continued focus on PTMs will pave the way for new possibilities in sepsis research and treatment.