Patients with cystic fibrosis (CF), an inherited exocrine disease, often face persistent respiratory infections Pseudomonas aeruginosaThis bacteria has a great capacity to adapt and survive in the host with cystic fibrosis. Once this colonization becomes chronic, P. aeruginosa It is difficult to eradicate completely. The bacteria often grow in biofilms trapped in the thick, viscous mucus rich in carbohydrates and DNA and on surfaces in the respiratory tract, evading host immune defenses and therapeutic interventions. P. aeruginosaIt is thought that, like other microorganisms, it uses lectins and other carbohydrate-binding proteins to attach to the host and connect to each other in self-established networks. Understanding how P. aeruginosa Binding to sugars in the cystic fibrosis airways may provide clues to developing new treatments that would limit these interactions and disrupt the connections that make antimicrobial agents so difficult to work with.
A recent study provides new insights into the carbohydrate binding patterns of this opportunistic pathogen Pseudomonas aeruginosa which poses a significant threat to the longevity and quality of life of people with cystic fibrosis. The research, conducted by Dr Deborah L. Chance and Dr Wei Wang, currently in the position, together with Dr James K. Waters and Professor Thomas P. Mawhinney, from the University of Missouri, aimed to inform the development of anti-adhesion therapies that could improve the treatment of persistent infections caused by this bacterium. The study was published in the peer-reviewed journal Microorganisms.
These colleagues from the Mawhinney Biomedical Research Team used multivalent fluorescent glycopolymers containing specific monosaccharides to analyze how different P. aeruginosa Strains from sources with and without cystic fibrosis interact with these carbohydrate structures. The researchers sought to determine whether the binding patterns of these bacteria vary based on their phenotypic characteristics or the clinical source from which they were isolated. “Our goal was to identify the key sugars that interact with Pseudomonas aeruginosa and see if this interaction differs between strains from various clinical settings,” Dr. Chance said.
The study revealed that P. aeruginosa Isolates from CF and non-CF sources demonstrated significant binding to glycopolymers with pendant α-D-galactose, β-DN-acetylgalactosamine, and β-D-galactose-3-sulfate. Employing advanced microscopic and spectrofluorometric techniques to profile carbohydrate binding patterns at the cellular level, the team found that specific carbohydrate confirmation (α or β) and the presence of specific chemical groups, such as the sulfate ester on β-D-galactose-3-sulfate, significantly influenced bacterial binding affinity. Furthermore, within each positive bacterial culture, a small subpopulation consistently accounted for the glycopolymer binding populations.
Interestingly, while the P. aeruginosa The specimens exhibited diverse colony morphologies and physiological activities, the binding profiles appeared consistent across all strains. None of the structural or other bacterial features could predict a more pronounced carbohydrate binding behavior. “These findings are crucial as they suggest that regardless of strain phenotype, P. aeruginosa “It maintains a small, persistent subpopulation that is adept at associating with very specific sugars,” Dr. Chance explained.
This P. aeruginosa The study of carbohydrate binding offers a valuable basis for designing therapies focused on disrupting bacterial interactions with the host and within biofilms and potentially targeting antimicrobial agents directly to the organism. Dr. Chance emphasized the complementary therapeutic potential of agents that target or disrupt the specific binding of monosaccharides of P. aeruginosa in the respiratory tract of patients with cystic fibrosis as tools to improve the efficacy of existing antibiotic treatments, especially in cases where multidrug resistance complicates conventional approaches.
Underscoring the importance of personalized treatment strategies for the management of cystic fibrosis, this research improves our understanding of the complex carbohydrate interactions involved when the characteristic heterogeneity of P. aeruginosa Dr. Chance notes that “a pleasant research surprise in the study of this very complex scenario of P. aeruginosa Adaptation and survival in the cystic fibrosis host was the persistence of specific binding patterns in the various bacterial populations. This suggests that targeted anti-adhesion or antimicrobial therapies could be universally effective against diverse bacterial populations. P. aeruginosa strains, regardless of their phenotypic diversity.”
In conclusion, the research conducted by Mawhinney's team marks a significant advance in the development of therapies targeting cystic fibrosis-related infections. By taking advantage of the unique carbohydrate binding profiles of P. aeruginosaFuture treatments could more effectively disrupt the colonization and persistence of this pathogen, ultimately improving the quality of life of people with CF.
Journal reference
Chance, DL, Wang, W., Waters, JK, Mawhinney, TP “Perspectives on Pseudomonas aeruginosa Carbohydrate binding from cystic fibrosis isolate profiles using multivalent fluorescent glycopolymers bearing pendant monosaccharides”. Microorganisms. 2024. DOI: https://doi.org/10.3390/microorganisms12040801
About the authors
A look at research at Mawhinney's biomedical research laboratories
Areas of specialization: Biochemistry, Analytical chemistry, Carbohydrate chemistry, Cystic fibrosis, Cancer, Microbiology
Specific focuses: Carbohydrates in cancer and bacterial infections; cancer prevention and treatment; host-pathogen interactions in cystic fibrosis; analytical methodologies.
Research at the Mawhinney Biomedical Research Laboratories focuses on a number of interrelated topics. In the area of exocrine defense mechanisms, with a particular emphasis on chronic obstructive pulmonary diseases in man, considerable effort has been made to develop a better understanding of mucosal glycoproteins as primary and secondary macromolecular defense responses against pulmonary pathogens and irritants.
Structural elucidation has provided important insights into altered post-translational modifications of the side chain oligosaccharides of respiratory mucins. The demonstration of significant increases in glycoprotein sulfation and anionicity, which parallel respiratory disease severity and chronicity, has been particularly pronounced in patients with the genetic disorder known as cystic fibrosis.
Ongoing research focuses the team’s chemical capabilities and expertise on discovering structure-function relationships in human and plant health and disease. In-house tools, along with those available through University of Missouri research centers, have enabled the integration of visual, biological, genetic, and chemical data into the discovery process to better understand human health and disease.
Team members in this study
Doctor Chance Dr. Chance earned her BS in Biology from Emory University, Atlanta, GA, followed by her MS and PhD in Biochemistry from the University of Missouri School of Medicine and the College of Agriculture, Food and Natural Resources. Dr. Chance continued her study of bacterial pathogenesis and cystic fibrosis through postdoctoral training with Arnold L. Smith, MD, PhD, and Chair of Molecular Microbiology and Immunology, at the University of Missouri School of Medicine, Columbia, Missouri. Dr. Chance is currently a Research Assistant Professor in Microbiology and Immunology and Pediatrics at the University of Missouri School of Medicine, Columbia, Missouri. Collaborating on cystic fibrosis and cancer research as part of the ESCL interdisciplinary Biomedical Research Team at CAFNR, Dr. Chance emphasizes research for a better understanding of opportunistic respiratory pathogens co-colonizing cystic fibrosis and their survival tactics in the human host. This research aims to help define new therapeutic strategies for chronic respiratory tract infections. Using clinically oriented basic research, often with patient samples, analytical, biochemical, molecular, microbiological, instrumental and imaging tools are applied to generate in vitro data from clinical situations faced by patients and physicians when addressing chronic infections and their treatment in cystic fibrosis. chanced@health.missouri.edu
Dr. Wang Dr. Wang received his medical training at Shandong University and his PhD in Biochemistry under Dr. Mawhinney at the University of Missouri, Columbia, Missouri. Dr. Wang continued his professional development with postdoctoral training at Peking University and an adjunct professorship at the School of Medicine, Shanghai Jiao Tong University. Currently, Dr. Wang is an Associate Professor in the School of Life Sciences, Fudan University. Focusing on the interface between chemistry and microbiology, Dr. Wang’s research focuses on developing novel chemical strategies to address complex bacterial systems closely related to human health. w_w@fudan.edu.cn
Dr. Waters He received his PhD in Biochemistry from the University of Missouri, Columbia, Missouri. He is currently a Research Chemist, QCO, and Analytical Services Supervisor at the Agricultural Experiment Station Chemical Laboratories (ESCL) within CAFNR, University of Missouri, Columbia, Missouri. ESCL@missouri.edu
With an analytical interest in plant, animal, and human health and nutrition, Dr. Waters’ chromatographic niche has focused on nutritional labeling, and together with his research colleague and biomedical research team member Dr. Valeri V. Mossine (https://cafnr.missouri.edu/directory/valeri-mossine/), Dr. Waters’ chemical syntheses have focused on versatile analytical standards and potentially useful therapeutics in inflammation and disease.
Dr MawhinneyDr. Mawhinney studied biochemistry at Fairleigh Dickinson University in New York, followed by graduate and dual PhD training in molecular biology and forensic pathology at Union University-Albany Medical Center in New York. In the area of cystic fibrosis pathology, he completed his postdoctoral training at the University of Missouri School of Medicine with Giulio Barbero, MD, Chair of the Department of Pediatrics. Dr. Mawhinney is currently a Professor of Biochemistry and Pediatrics at the University of Missouri College of Agriculture, Food and Natural Resources (CAFNR) and the University of Missouri School of Medicine, Columbia, Missouri. Dr. Mawhinney also serves as Missouri State Chemist and Director of Analytical Services for the Agricultural Experiment Station Chemical Laboratories (ESCL) within the CAFNR, University of Missouri, Columbia, Missouri. ESCL@missouri.eduWith a passion for teaching and research, Dr. Mawhinney continues as a lifelong learner and educator at the University of Missouri School of Medicine and facilitator of agricultural and medical research worldwide through ESCL outreach. mawhinneyt@missouri.edu
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