Treatment of bacterial infections has become a serious clinical challenge with the global emergence of antibiotic resistance. The weakening efficacy of antibiotic therapies necessitates alternative treatment strategies that aim to captivate the virulence mechanisms that cause bacterial infections. Our goal is to identify new bioavailable small molecules as preclinical candidate for chronic infection (Pyelonephritis). Uropathogenic Escherichia coli (UPEC) employ various chaperone-usher pathway (CUP) pili of diverse ligand specificities, which bind distinct positions within the human host to establish and maintain urinary tract infections (UTIs). Noteworthy among CUP pili are F9 pili, which UPEC expression order to bind Gal-β1-3-GalNAc (TF) epitope-containing bladder epithelial receptors, induced upon inflammation during chronic, unresolved UTI. We rationally designed new small molecule Galactosides that specifically bind to the FmlH (lectin) and inhibit the function of the F9 pilus adhesion. A combination of structure-guided design, and ELISA-based assay led to the discovery of lead candidate. Pseudomonas aeruginosa is a prevalent and troublesome opportunistic Gram-negative bacterium that is capable of colonizing various human tissues and organs and is often resistant to many currently used antibiotics. P. aeruginosa has become a severe threat for hospitalized immuno-compromised patients and is now a critical priority 1 pathogen as stated by the WHO in 2017. In persons suffering from cystic fibrosis, chronic infections with this pathogen lead to recurrent pneumonia, sepsis, and lung damage. Infections of various organs and tissues by this pathogen, such as chronic wound or catheter-associated urinary tract infections (caUTI), impose severe clinical challenges which further result from the bacterium’s intrinsic drug resistance and additional acquired resistances often leading to multi-drug-resistant or extremely drug-resistant strains. LecA and LecB are two virulence factors, these two are proteins/lectins are carbohydrate binding pockets formed the biofilm by P. aeruginosa. The lectins LecA and LecB that bind galactose and fucose, as well as oligo- and polysaccharides containing these sugars, are among the most thoroughly-studied targets for such novel antibacterial. We used X-ray crystal structure and designed and developed small molecule galactose potent inhibitors for treating theses bacterial infections.

Developing the new class of antagonists to prevent recurrent urinary tract infections (UTIs), kidney diseases and Pseudomonas aeruginosa by targeting Escherichia coli bacteria and Gram-negative bacterium

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.