Patients with the inherited exocrine disease cystic fibrosis (CF) often face persistent respiratory infections with Pseudomonas aeruginosa. This bacterium has a keen aptitude for adapting to and surviving in the CF host. Once this colonization becomes chronic, P. aeruginosa is difficult to ever completely eradicate. Often growing in biofilms trapped in the thick viscous carbohydrate- and DNA-rich mucus and on the surfaces of the respiratory tract, the bacterium evades the host immune defenses and therapeutic interventions. P. aeruginosa, like other microorganisms, is thought to use lectins and other carbohydrate binding proteins to attach to the host and to connect with one another in self-established networks. Understanding how P. aeruginosa binds to sugars in the CF airway may provide guiding clues in the development of new treatments that would limit these interactions and disrupt the connections that make success of antimicrobial agents so difficult.
A recent study provides new insights into the carbohydrate binding patterns of this opportunistic pathogen Pseudomonas aeruginosa that poses a significant threat to the longevity and quality of life of individuals with CF. The research, conducted by Deborah L. Chance, PhD and Wei Wang, now PhD, along with James K. Waters, PhD, and Professor Thomas P. Mawhinney, PhD, at the University of Missouri, aimed to inform the development of anti-adhesive 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 in the Mawhinney Biomedical Research Team utilized multivalent fluorescent glycopolymers bearing specific monosaccharides to analyze how different P. aeruginosa strains from CF and non-CF sources 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 to see if this interaction differs among strains from various clinical settings,” said Dr. Chance.
The study revealed that P. aeruginosa isolates from both CF and non-CF sources demonstrated significant binding to glycopolymers with pendant α-D-galactose, β-D-N-acetylgalactosamine, and β-D-galactose-3-sulfate. Employing advanced microscopic and spectrofluorometric techniques to profile the carbohydrate-binding patterns at the cellular level, the team found that the specific confirmation of the carbohydrate (α or β) and the presence of specific chemical groups, such as the sulfate ester in β-D-galactose-3-sulfate, significantly influenced the binding affinity of the bacteria. Additionally, within each positive bacterial culture a small subpopulation consistently accounted for the populations’ glycopolymer binding.
Interestingly, while the P. aeruginosa specimens exhibited diverse colony morphologies and physiological activities, the binding profiles appeared consistent across the strains. None of structural or other bacterial characteristics could predict more pronounced carbohydrate-binding behavior. “These findings are crucial as they suggest that regardless of the strain’s phenotype, P. aeruginosa maintains a small, persistent subpopulation that is adept at associating with very specific sugars,” Dr. Chance explained.
This P. aeruginosa carbohydrate binding survey offers a valuable foundation for designing therapies focused on disrupting the bacterial interactions with the host and within biofilms and potentially targeting antimicrobial agents directly to the organism. Dr. Chance emphasized the adjunctive therapeutic potential of agents targeting or disrupting the specific monosaccharide binding of P. aeruginosa in the respiratory tract of CF patients as tools to enhance the effectiveness of existing antibiotic treatments, especially in cases where multidrug resistance complicates conventional approaches.
Underscoring the importance of personalized treatment strategies in managing CF, this research enhances our understanding of the complex carbohydrate interactions involved when the characteristic heterogeneity of P. aeruginosa is encountered. Dr. Chance notes that “a pleasant research surprise in the study of this very complex scenario of P. aeruginosa adaptation and survival in the CF host, was the persistence of specific binding patterns across the diverse bacterial populations. This suggests that targeted anti-adhesive or anti-microbial therapeutics could be universally effective against various P. aeruginosa strains, regardless of their phenotypic diversity”.
In conclusion, the research conducted by the Mawhinney Team marks a significant step forward in the development of targeted therapies for CF-related infections. By leveraging the unique carbohydrate-binding profiles of P. aeruginosa, future treatments could more effectively disrupt the colonization and persistence of this pathogen, ultimately improving the quality of life for individuals with CF.
Journal Reference
Chance, D.L., Wang, W., Waters, J.K., Mawhinney, T.P. “Insights on Pseudomonas aeruginosa Carbohydrate Binding from Profiles of Cystic Fibrosis Isolates Using Multivalent Fluorescent Glycopolymers Bearing Pendant Monosaccharides.” Microorganisms. 2024. DOI: https://doi.org/10.3390/microorganisms12040801
About the Authors
Research at a glance in the Mawhinney Biomedical Research Laboratories
Area(s) of Expertise: Biochemistry, Analytical Chemistry, Carbohydrate Chemistry, Cystic Fibrosis, Cancer, Microbiology
Specific Focuses: Carbohydrates in cancer and bacterial infection; cancer prevention and treatment; host-pathogen interactions in cystic fibrosis; analytical methodologies.
Research in the Mawhinney Biomedical Research Laboratories focuses on a number of interrelated topics. In the area of exocrine defense mechanisms, with special emphasis on chronic obstructive pulmonary diseases in man, a sizable effort has been trained on developing a better understanding of mucous glycoproteins as a primary and secondary macromolecular defense response against lung pathogens and irritants.
Structural elucidation has yielded significant insights into altered post-translational modifications of the side chain oligosaccharides of respiratory mucins. Demonstration of significant increases in glycoprotein sulfation and anionicity, that parallel the severity of the respiratory disease and its chronicity, have been particularly pronounced in patients with the genetic disorder known as cystic fibrosis.
Ongoing research focuses the team’s abilities and chemical expertise on the discovery of structure-function relationships in human and plant health and disease. In-house tools coupled with those available through research cores in at the University of Missouri have permitted the integration of visual, biological, genetic and chemical data in the discovery process for better understanding human health and disease.
Team Members on this Study
Dr. Chance received her BS in Biology at Emory University, Atlanta, GA, followed by her MS & PhD in Biochemistry at the University of Missouri School of Medicine and the College of Agriculture, Food & Natural Resources. Dr. Chance pursued her study of bacterial pathogenesis and cystic fibrosis through Postdoctoral training with Dr. Arnold L. Smith, MD, PhD, and Chair of Molecular Microbiology & Immunology, at University of Missouri School of Medicine, Columbia, Missouri. Dr. Chance is currently an Adjunct Assistant Research Professor in Microbiology & Immunology and Pediatrics at the University of Missouri School of Medicine, Columbia, Missouri.Collaborating on cystic fibrosis and cancer research as part of the interdisciplinary Biomedical Research Team of the ESCL in CAFNR, Dr. Chance emphases research toward better understanding of the co-colonizing respiratory opportunistic pathogens of cystic fibrosis and their survival tactics in the human host. This research is intended to help define new therapeutic strategies for chronic airway infections. Using clinically minded basic research, often with patient specimens, analytical, biochemical, molecular, microbiological, instrumental, imaging tools are applied to generate in vitro data from clinical situations encountered by patients and physicians when addressing chronic infection and its treatment in cystic fibrosis. chanced@health.missouri.edu
Dr. Wang received his medical training at Shandong University, and his PhD in Biochemistry with Dr. Mawhinney at the University of Missouri, Columbia, Missouri. Dr. Wang continued is professional development with Postdoctoral training at Peking University, and an Assistant Professorship at Shanghai Jiao Tong University School of Medicine. Currently Dr. Wang is an Associate Professor at School of Life Sciences, Fudan University.Residing on the interface between chemistry and microbiology, Dr. Wang’s research focuses on developing new chemical strategies to approach complex bacterial systems tightly related to human health. w_w@fudan.edu.cn
Dr. Waters received his PhD in Biochemistry at the University of Missouri, Columbia, Missouri. He is currently a Research Chemist, QCO and Supervisor of the Analytical Services of the Agricultural Experiment Station Chemical Laboratories (ESCL) within the CAFNR, University of Missouri, Columbia, Missouri. ESCL@missouri.edu
With an analytical interest in health and nutrition of plants, animals and humans, Dr. Waters’s chromatographic niche has focused in nutritional labeling, and along with research colleague and biomedical research team member Dr. Valeri V. Mossine (https://cafnr.missouri.edu/directory/valeri-mossine/), Dr. Water’s chemical syntheses have targeted versatile analytical standards and potentially useful therapeutics in inflammation and disease.
Dr. Mawhinney’s early chemical educational background included biochemistry training at Fairleigh Dickinson University in New York, followed by graduate study and a dual PhD in Molecular Biology and Forensic Pathology at Union University, Albany Medical Center, New York. Addressing the pathology of cystic fibrosis, Dr. Mawhinney completed his postdoctoral training at the University of Missouri School of Medicine with Dr. Giulio Barbero, MD, Chair, Department of Pediatrics. Currently Dr. Mawhinney is Professor of Biochemistry and Pediatrics in the University of Missouri College of Agriculture, Food and Natural Resources (CAFNR) and in the University of Missouri School of Medicine, Columbia, Missouri. Dr. Mawhinney also serves as the Missouri State Chemist and Director of the Analytical Services of 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 in the School of Medicine of the University of Missouri and facilitator of agricultural and medical researcher around the globe through the outreach of the ESCL. mawhinneyt@missouri.edu
