AI Article Synopsis

  • - CU fimbriae are prevalent in Gram-negative bacteria, with 38 types identified, and some types can bind to specific glycan targets, promoting colonization in host tissues, like bladder tissue via type 1 fimbriae.
  • - Researchers used a recombinant bacterial strain and glycan array analysis to determine the receptor specificity of six different CU fimbriae, revealing their binding affinities through a technique called surface plasmon resonance.
  • - This study enhances our understanding of bacterial adhesion mechanisms, highlights potential new methods to combat antibiotic resistance through adhesion blocking, and identifies glycan receptors that align with known fimbrial functions.

Article Abstract

Chaperone-usher (CU) fimbriae are the most abundant Gram-negative bacterial fimbriae, with 38 distinct CU fimbria types described in alone. Some CU fimbriae have been well characterized and bind to specific glycan targets to confer tissue tropism. For example, type 1 fimbriae bind to α-d-mannosylated glycoproteins such as uroplakins in the bladder via their tip-located FimH adhesin, leading to colonization and invasion of the bladder epithelium. Despite this, the receptor-binding affinity of many other CU fimbria types remains poorly characterized. Here, we used a recombinant strain expressing different CU fimbriae, in conjunction with glycan array analysis comprising >300 glycans, to dissect CU fimbria receptor specificity. We initially validated the approach by demonstrating the purified FimH lectin-binding domain and recombinant expressing type 1 fimbriae bound to a similar set of glycans. This technique was then used to map the glycan binding affinity of six additional CU fimbriae, namely, P, F1C, Yqi, Mat/Ecp, K88, and K99 fimbriae. The binding affinity was determined using whole-bacterial-cell surface plasmon resonance. This work describes new information in fimbrial specificity and a rapid and scalable system to define novel adhesin-glycan interactions that underpin bacterial colonization and disease. Understanding the tropism of pathogens for host and tissue requires a complete understanding of the host receptors targeted by fimbrial adhesins. Furthermore, blocking adhesion is a promising strategy to counter increasing antibiotic resistance and is enabled by the identification of host receptors. Here, we use a defined heterologous expression system to identify glycan receptors for six chaperone-usher fimbriae and identify novel receptors that are consistent with their known function. The same system was used to measure the kinetics of binding to the identified glycan, wherein bacterial cells were immobilized onto a biosensor chip and the interactions with glycans were quantified by surface plasmon resonance. This novel, dual-level analysis, where screening for the repertoire of glycan binding and the hierarchy of affinity of the identified ligands is determined directly from a natively expressed fimbrial structure on the bacterial cell surface, is superior in both throughput and biological relevance.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545135PMC
http://dx.doi.org/10.1128/mBio.03664-20DOI Listing

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