Archives des Case study of Glycomimetics against Multi-Drug Resistant Pathogens

Abstract

Multi-drug resistant (MDR) pathogens such as Burkholderia cenocepacia have become a hazard in the context of healthcare-associated infections, especially for patients admitted

Table 1. The race between antibiotic development and AMR. Adapted from the U.S. Centers for Disease Control and Prevention.(US-CDC, 2019)

The problem of antimicrobial resistance (AMR)

The problem of antimicrobial resistance (AMR) Many barriers have been met and overcome across the history of the human race

Figure 1. Schematic representation of bacterial adhesion to epithelial cells and the anti-adhesion strategy. A detail of the workings of anti-adhesion therapy is presented in Figure 5.

Anti-adhesion therapy (AAT), a possible solution

In order to act efficiently, infective pathogens need to interact with their environment. First and foremost, a virus or a

Figure 2. Left: Electron microscopy picture of the endothelial glycocalyx. Right: Schematic depiction of the glycocalyx and some of its roles. Glycoconjugates and oligosaccharide epitopes are schematized at the surface of an epithelial cell. Adapted from Zausig and co-workers (2013). (Zausig et al., 2013)

The role of lectins and carbohydrates in infection

Human epithelial cells are found at the forefront of human anatomy separate the body and its cavities from the exterior

Figure 6. Examples of monovalent glycomimetics. Adapted from Tamburrini and co-workers (2020). (Tamburrini et al., 2020)

Glycans and Glycomimetics as therapeutic agents

On paper, the concept of using naturally occurring carbohydrates in AAT can be considered a revamping of the successful story

Figure 9. Scanning electron microscopy (SEM) images of P. aeruginosa PAO1 and B. cenocepacia K56-2 cells. Top left: P. aeruginosa biofilm on a granite pebble, scale: 10Î¼m. Top middle: Magnification on P. aeruginosa cells, scale: 1Î¼m. Top right: Magnification on B. cenocepacia cells. Bottom: B. cenocepacia adhesion to human bronchial epithelial cells (cell line 16HBE14o-). Adapted from Whiteley and co-workers (2001) and Pimenta and co-workers (2021).(Pimenta et al., 2021; Whiteley et al., 2001)

Opportunistic lung pathogens: Burkholderia cenocepacia and company

As previously mentioned, multidrug-resistant (MDR) pathogens are a constant threat to hospitalized patients, especially those with risk factors such as

Lectins of B. cenocepacia: the BC2L family

As mentioned earlier, lectins are key actors in cell adhesion leading to infection and have proven to be interesting anti-adhesion

Table 2. Affinities measured by ITC for different ligands of the two domains of BC2L-C. Standard deviations are below 5%. Adapted from Šulák and co-workers (2010 and 2011). (Sulak et al., 2010; Sulak et al., 2011)

The superlectin BC2L-C: state of the art

Like BC2L-A, the protein BC2L-C is a “Lec-B” like lectin: its C-terminal domain is 116 residues long and shares 43%

References

Conclusion

In conclusion, two undeniable truths must be considered: antimicrobial resistance is becoming a critical problem for modern medicine, and the

The Author

Rafael Bermeo Born and raised in Ecuador, Rafael Bermeo moved to France in 2011 to attend the Lyon Superior School