The Kdo biosynthetic pathway toward OM biogenesis as target in antibacterial drug design and development.
Despite important advances made in the last century, infectious diseases caused by pathogenic microrganisms are still a major threat to human health. This is worsened by the occurrence of new forms of bacterial resistance against antibiotics, that are the main remedy against infectious diseases, and their rapid spreading across bacterial species, pose additional threats to our health. Thus, the necessity to develop new weapons against pathogenic bacteria is widely recognized as a major challenge for modern drug research. Traditional antibiotic discovery procedures have so far focused on inhibiting the main processes of the bacterial cell (replication, transcription, translation, and peptidoglycan synthesis). This review will give an overview of the therapeutic strategies to cure infectious diseases caused by Gram-negative bacteria through the development of inhibitors of Kdo biosynthesis. Kdo is a monsaccharide essential for OM biogenesis, OM being an essential cellular structure shared by all Gram-negative bacteria. Hence, inhibitors of its biosynthesis can have a broad-spectrum antibacterial activity.
Cipolla
Laura
L
Department of Biotechnology and Biosciences, University of Milano-Bicocca, P.za della Scienza 2, 20126 Milano, Italy. laura.cipolla@unimib.it
Polissi
Alessandra
A
Airoldi
Cristina
C
Galliani
Paolo
P
Sperandeo
Paola
P
Nicotra
Francesco
F
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000187:drug effects; D016503:Drug Delivery Systems; D015195:Drug Design; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D013400:Sugar Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D008070:Lipopolysaccharides; D013400:Sugar Acids; C120356:3-deoxy-manno-oct-2-ulopyranosonic acid