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Microbial adhesion to medical devices is common for hospital-acquired infections, particularly for urinary catheters. If not properly treated these infections cause complications and exacerbate antimicrobial resistance. Catheter use elicits bladder inflammation, releasing host serum proteins, including fibrinogen (Fg), into the bladder, which deposit on the urinary catheter.Enterococcus faecalisuses Fg as a scaffold to bind and persist in the bladder despite antibiotic treatments. Inhibition of Fg–pathogen interaction significantly reduces infection. Here, we show deposited Fg is advantageous for uropathogensE. faecalis,Escherichia coli,Pseudomonas aeruginosa,K. pneumoniae,A. baumannii, andC. albicans, suggesting that targeting catheter protein deposition may reduce colonization creating an effective intervention for catheter-associated urinary tract infections (CAUTIs). In a mouse model of CAUTI, host-protein deposition was reduced, using liquid-infused silicone catheters, resulting in decreased colonization on catheters, in bladders, and dissemination in vivo. Furthermore, proteomics revealed a significant decrease in deposition of host-secreted proteins on liquid-infused catheter surfaces. Our findings suggest targeting microbial-binding scaffolds may be an effective antibiotic-sparing intervention for use against CAUTIs and other medical device infections.
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Marine-Derived Sulfated Glycans Inhibit the Interaction of Heparin with Adhesion Proteins of Mycoplasma pneumoniae
Mycoplasma pneumoniae, a notable pathogen behind respiratory infections, employs specialized proteins to adhere to the respiratory epithelium, an essential process for initiating infection. The role of glycosaminoglycans, especially heparan sulfate, is critical in facilitating pathogen–host interactions, presenting a strategic target for therapeutic intervention. In this study, we assembled a glycan library comprising heparin, its oligosaccharide derivatives, and a variety of marine-derived sulfated glycans to screen the potential inhibitors for the pathogen–host interactions. By using Surface Plasmon Resonance spectroscopy, we evaluated the library’s efficacy in inhibiting the interaction between M. pneumoniae adhesion proteins and heparin. Our findings offer a promising avenue for developing novel therapeutic strategies against M. pneumoniae infections.
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- Award ID(s):
- 1933525
- PAR ID:
- 10609122
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Marine Drugs
- Volume:
- 22
- Issue:
- 5
- ISSN:
- 1660-3397
- Page Range / eLocation ID:
- 232
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/md22050232
