title: Innovative Solutions to Sticky Situations: Antiadhesive Strategies for Treating Bacterial Infections.
abstract: Bacterial adherence to host tissue is an essential process in pathogenesis, necessary for invasion and colonization and often required for the efficient delivery of toxins and other bacterial effectors. As existing treatment options for common bacterial infections dwindle, we find ourselves rapidly approaching a tipping point in our confrontation with antibiotic-resistant strains and in desperate need of new treatment options. Bacterial strains defective in adherence are typically avirulent and unable to cause infection in animal models. The importance of this initial binding event in the pathogenic cascade highlights its potential as a novel therapeutic target. This article seeks to highlight a variety of strategies being employed to treat and prevent infection by targeting the mechanisms of bacterial adhesion. Advancements in this area include the development of novel antivirulence therapies using small molecules, vaccines, and peptides to target a variety of bacterial infections. These therapies target bacterial adhesion through a number of mechanisms, including inhibition of pathogen receptor biogenesis, competition-based strategies with receptor and adhesin analogs, and the inhibition of binding through neutralizing antibodies. While this article is not an exhaustive description of every advancement in the field, we hope it will highlight several promising examples of the therapeutic potential of antiadhesive strategies.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Cusumano
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Klein
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001419:Bacteria / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D001422:Bacterial Adhesion / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology* / Q000517:prevention & control; D018441:Biofilms / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D006801:Humans; D058990:Molecular Targeted Therapy
chemical_list: D000900:Anti-Bacterial Agents