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Therapeutic Horizons of Oligosaccharides: Molecular Mechanisms and Therapeutic Potential

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 20 June 2026 | Viewed by 3102

Special Issue Editors


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Guest Editor
1. Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, 18011 Granada, Spain
2. Instituto de Investigación Biosanitaria (IBS), 18014 Granada, Spain
3. Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. Armilla, 18016 Granada, Spain
Interests: nutrition and dietetics nutritional; biochemistry; pharmacy; cell biology; molecular biology; immunology; regulation of the gene expression in prokaryotes and eukaryotes; pathogens; enzymology and biotechnology
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Guest Editor
Biosanitary Research Institute of Granada (ibs.GRANADA), Granada, Spain
Interests: pharmaceutical; biomedical

Special Issue Information

Dear Colleagues,

Oligosaccharides, a diverse class of complex carbohydrates, play a crucial role in modulating host–microorganism interactions across a wide range of biological contexts. These structurally intricate molecules influence the immune response and key microbial processes such as adhesion, biofilm formation, immune evasion, and intercellular communication, including quorum sensing. Derived from both natural and synthetic sources, oligosaccharides can mimic host glycans, disrupt the expression of virulence factors, and alter microbial community dynamics, thereby interfering with colonization and pathogenic behavior in various microorganisms.

Recent advances in glycomics, microbiology, and biomedical sciences have highlighted oligosaccharides as promising candidates for the development of novel therapeutic strategies, particularly in the fight against multidrugresistant (MDR) pathogens. Their ability to inhibit pathogen attachment, attenuate virulence, and modulate the microbiome without exerting the selective pressure that drives antimicrobial resistance makes them attractive alternatives to conventional antimicrobials. Human milk oligosaccharides (HMOs) have been extensively studied for their protective functions in early life, exhibiting strong antiadhesive and immunomodulatory properties against enteric and respiratory pathogens. Moreover, advancements in glycoengineering have enabled the synthesis of bioactive oligosaccharide analogs with enhanced therapeutic potential, supporting the development of precision-based antimicrobial approaches.

In addition to their antimicrobial effects, oligosaccharides have demonstrated a capacity to modulate inflammatory responses, particularly within the intestinal environment. Certain oligosaccharides can influence immune cell signaling and cytokine production, helping to restore intestinal homeostasis and reduce inflammation. For example, specific prebiotic oligosaccharides have been shown to downregulate proinflammatory mediators such as TNF-α, IL-6, and IL-1β, while promoting anti-inflammatory cytokines like IL-10. These immunomodulatory effects are often mediated through interactions with gut-associated lymphoid tissue and modulation of the gut microbiota, highlighting their potential in managing inflammatory bowel diseases and other gut-related disorders.

This Special Issue explores the multifaceted roles of oligosaccharides in host–microbe interactions and immune signaling, with a focus on their structural diversity, mechanisms of action, and translational applications. We welcome original and innovative research on oligosaccharide-mediated modulation of immune responses, antimicrobial and antibiofilm properties, glycoengineering, microbiota modulation, and clinical implementation.

This Special Issue aims to enhance our understanding of how oligosaccharides influence intestinal barrier function and susceptibility to infection, with the goal of informing the development of more effective preventive and therapeutic approaches for common systemic and intestinal diseases and emphasizing their promise in next-generation biomedical interventions.

Prof. Dr. Abdelali Daddaoua
Dr. María Núñez-Núñez
Guest Editors

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Keywords

  • oligosaccharides
  • bacterial infection
  • multidrug-resistant

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Published Papers (2 papers)

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Research

17 pages, 1308 KB  
Communication
Anti-Pneumococcal Properties of the Native Human Milk Oligosaccharide Fraction: A Concentration-Dependent Study
by Oliwia Makarewicz, Tinatini Tchatchiashvili, Lisa Jasef, Mark P. G. van der Linden, Sylwia Jarzynka, Kamila Strom, Nico Ueberschaar, Maciej Mazur, Gabriela Oledzka and Mathias W. Pletz
Int. J. Mol. Sci. 2025, 26(21), 10781; https://doi.org/10.3390/ijms262110781 - 6 Nov 2025
Viewed by 718
Abstract
Streptococcus pneumoniae is a major opportunistic pathogen and a leading cause of severe infections in infants under two years of age. Human milk oligosaccharides (HMOs), key bioactive components of breast milk, possess immunomodulatory and antimicrobial properties. In this study, the antipneumococcal effects of [...] Read more.
Streptococcus pneumoniae is a major opportunistic pathogen and a leading cause of severe infections in infants under two years of age. Human milk oligosaccharides (HMOs), key bioactive components of breast milk, possess immunomodulatory and antimicrobial properties. In this study, the antipneumococcal effects of HMOs are investigated across multiple S. pneumoniae serotypes, focusing on concentration-dependent activity and underlying mechanisms. Growth inhibition and bacterial viability were evaluated using growth curve analysis and colony-forming unit (CFU) assays. HMOs inhibited pneumococcal growth in a concentration-dependent manner, with suppression observed at 1.5–2.5 mg/mL and complete killing at 5 mg/mL for all serotypes. Nonencapsulated strains were more sensitive, with inhibition at 1 mg/mL. In the CFU assays, killing occurred at 1.25–5 mg/mL depending on the strain. At physiologically relevant colostrum concentrations (20–25 mg/mL), HMOs achieved complete bactericidal effects across all the tested strains. In contrast, lactose at equivalent doses showed no measurable antimicrobial activity, confirming the specificity of the observed effects. Overall, HMOs exhibit serotype-independent antipneumococcal activity, possibly through interference with bacterial adhesion or metabolic disruption. These findings suggest a potential role for HMOs as adjunctive agents in the prevention of pneumococcal infections in vulnerable populations, such as infants, and warrant further in vivo studies to validate these effects and explore clinical applications. Full article
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26 pages, 3148 KB  
Article
Transcriptional Regulatory Systems in Pseudomonas: A Comparative Analysis of Helix-Turn-Helix Domains and Two-Component Signal Transduction Networks
by Zulema Udaondo, Kelsey Aguirre Schilder, Ana Rosa Márquez Blesa, Mireia Tena-Garitaonaindia, José Canto Mangana and Abdelali Daddaoua
Int. J. Mol. Sci. 2025, 26(10), 4677; https://doi.org/10.3390/ijms26104677 - 14 May 2025
Cited by 1 | Viewed by 1863
Abstract
Bacterial communities in diverse environmental niches respond to various external stimuli for survival. A primary means of communication between bacterial cells involves one-component (OC) and two-component signal transduction systems (TCSs). These systems are key for sensing environmental changes and regulating bacterial physiology. TCSs, [...] Read more.
Bacterial communities in diverse environmental niches respond to various external stimuli for survival. A primary means of communication between bacterial cells involves one-component (OC) and two-component signal transduction systems (TCSs). These systems are key for sensing environmental changes and regulating bacterial physiology. TCSs, which are the more complex of the two, consist of a sensor histidine kinase for receiving an external input and a response regulator to convey changes in bacterial cell physiology. For numerous reasons, TCSs have emerged as significant targets for antibacterial drug design due to their role in regulating expression level, bacterial viability, growth, and virulence. Diverse studies have shown the molecular mechanisms by which TCSs regulate virulence and antibiotic resistance in pathogenic bacteria. In this study, we performed a thorough analysis of the data from multiple public databases to assemble a comprehensive catalog of the principal detection systems present in both the non-pathogenic Pseudomonas putida KT2440 and the pathogenic Pseudomonas aeruginosa PAO1 strains. Additionally, we conducted a sequence analysis of regulatory elements associated with transcriptional proteins. These were classified into regulatory families based on Helix-turn-Helix (HTH) protein domain information, a common structural motif for DNA-binding proteins. Moreover, we highlight the function of bacterial TCSs and their involvement in functions essential for bacterial survival and virulence. This comparison aims to identify novel targets that can be exploited for the development of advanced biotherapeutic strategies, potentially leading to new treatments for bacterial infections. Full article
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