Bacterial adhesion--a source of alternate antibiotic targets.
The prevalence of antibiotic resistance among microorganisms that cause infectious diseases has resulted in the need to devise new strategies for the development of novel therapeutics. In an effort to thwart antibiotic resistance, novel therapeutics are being developed that target bacterial virulence factors as an alternative to traditional antibiotics, which target essential microbial processes, thereby promoting bacterial evolution and resulting in resistance. While many antivirulence targets exist, this feature review focuses on adhesion as an antivirulence target, using pili of uropathogenic Escherichia coli as a model system. The two strategies of drug development discussed in this review involve the inhibition of bacterial binding to the host tissue by the addition of exogenous sugars, and the disruption of chaperone-usher (CU) pilus assembly through the disruption of protein-protein interactions. However, because of the commonality of adhesion to infectious disease processes and CU pili to many pathogens, the two strategies are translatable to a multitude of organisms.
Washington University School of Medicine, Department of Molecular Microbiology and Microbial Pathogenesis, 660 South Euclid Avenue, St Louis, MO 63110, USA.
Corinne K
CK
Cusumano
Scott J
SJ
Hultgren
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000472:pathogenicity; D001422:Bacterial Adhesion / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D016503:Drug Delivery Systems; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans
D000900:Anti-Bacterial Agents