Targeting Polyamine Metabolism in Human Intracellular Pathogens Colonizing Macrophages—Connecting the Dots Between Mycobacterium, Leishmania and Plasmodium
Year: 2026
Type: article
Abstract: Polyamine metabolism has emerged as an important factor in pathogen survival, proliferation, virulence and persistence, highlighting polyamine-associated proteins and metabolic pathways as promising therapeutic targets. This is particularly relevant to major infectious diseases, including tuberculosis, malaria, leishmaniasis, and trypanosomiasis, in which pathogens exploit and remodel host cellular processes to evade immune responses and establish intracellular survival. Increasing evidence indicates that alterations in host–pathogen polyamine metabolism contribute to pathogen adaptation and persistence, providing opportunities for therapeutic intervention. Over the past decade, several components of polyamine biosynthesis, transport, and utilization have been identified and validated as potential drug targets in clinically relevant pathogens. Concurrently, advances in medicinal chemistry have led to the development of polyamine-derived compounds with enhanced specificity toward pathogen-associated polyamine proteins and metabolic pathways. These advancements have improved approaches to target-based drug discovery, which can be a novel complementary strategy to conventional antimicrobial development. This is particularly relevant in the context of the increasing prevalence of multidrug-resistant (MDR) pathogens. In this review, recent advances in the identification and validation of polyamine-related drug targets in pathogens causing tuberculosis, malaria, leishmaniasis, and trypanosomiasis are summarized. Furthermore, emerging strategies for the design and optimization of polyamine-derived therapeutic compounds, with a focus on their molecular targets, mechanisms of action, and potential for combating antimicrobial resistance, are discussed. Current challenges and future opportunities for targeting polyamine metabolism in the development of next-generation therapeutics are highlighted.:
Source: Pathogens
Author: Sergii Krysenko
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,654
OpenAlex ID: W7213443104