Nejvíce citovaný článek - PubMed ID 16793551
Carbohydrates are essential mediators of many processes in health and disease. They regulate self-/non-self- discrimination, are key elements of cellular communication, cancer, infection and inflammation, and determine protein folding, function and life-times. Moreover, they are integral to the cellular envelope for microorganisms and participate in biofilm formation. These diverse functions of carbohydrates are mediated by carbohydrate-binding proteins, lectins, and the more the knowledge about the biology of these proteins is advancing, the more interfering with carbohydrate recognition becomes a viable option for the development of novel therapeutics. In this respect, small molecules mimicking this recognition process become more and more available either as tools for fostering our basic understanding of glycobiology or as therapeutics. In this review, we outline the general design principles of glycomimetic inhibitors (Section 2). This section is then followed by highlighting three approaches to interfere with lectin function, i.e. with carbohydrate-derived glycomimetics (Section 3.1), novel glycomimetic scaffolds (Section 3.2) and allosteric modulators (Section 3.3). We summarize recent advances in design and application of glycomimetics for various classes of lectins of mammalian, viral and bacterial origin. Besides highlighting design principles in general, we showcase defined cases in which glycomimetics have been advanced to clinical trials or marketed. Additionally, emerging applications of glycomimetics for targeted protein degradation and targeted delivery purposes are reviewed in Section 4.
The presence of a diversity of virulence factors such as Chaperone-Usher (CU) fibers in uropathogenic Escherichia coli (UPEC) pathotypes virulome has offered these bacteria a unique opportunity to select the right factors in suitable condition. Understanding the structures and mechanisms of these infectious weapons enables us to prevent the occurrence of infections and/or to treat the urinary tract infections (UTIs) with effective methodologies. This review summarizes the current knowledge on the mechanisms of CU fimbriae (CUF) formation in UPEC. Several CU fibers including Auf, Dr, F1C, S, Type 9, Type 3, Type 1, and P fimbriae have been recognized in UPEC pathotypes. These fimbrial organelles may have cross-talk with each other in the presence of different environmental factors. In other words, the expression or the silence of their genes are associated with a wide range of items comprising environmental factors, genetical factors, physiological factors, etc. Recognition, detection, and identification of virulome and the related characteristics, properties, and mechanisms in UPEC enable us to create new methodologies to have a definite prevention and treatment for UTIs in this regard.
- Klíčová slova
- Bacterial fimbriae, Urinary tract infection, Uropathogenic Escherichia coli,
- MeSH
- bakteriální adheze * MeSH
- bakteriální fimbrie genetika metabolismus MeSH
- biofilmy MeSH
- faktory virulence genetika MeSH
- infekce močového ústrojí mikrobiologie MeSH
- infekce vyvolané Escherichia coli mikrobiologie MeSH
- lidé MeSH
- proteiny fimbrií genetika metabolismus MeSH
- proteiny z Escherichia coli metabolismus MeSH
- uropatogenní Escherichia coli genetika patogenita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- faktory virulence MeSH
- proteiny fimbrií MeSH
- proteiny z Escherichia coli MeSH