title: Important Complexities of the Antivirulence Target Paradigm: A Novel Ostensibly Resistance-Avoiding Approach for Treating Infections.
abstract: Use of antivirulence therapy has assumed that inhibition of bacterial fitness at the site of infection without directly affecting viability will minimize the development of resistance. However, selection for resistant strains is much more likely to occur at sites of colonization or in the environment following excretion of the therapeutic agent. Data are needed regarding whether the drug's target promotes fitness among bacteria in (drug-exposed) niches other than sites of infection. Furthermore, in vivo studies of resistance selection should assess off-target selection for resistance (eg, within the microbiome). Only when such data are available can the risk for development of resistance be gauged appropriately.
authors.affiliation: Veterans Administration Western New York Healthcare System Department of Medicine Department of Microbiology and Immunology Witebsky Center for Microbial Pathogenesis, University at Buffalo-State University of New York, New York.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Russo
authors.affiliation: Los Angeles County-University of Southern California (USC) Medical Center Division of Infectious Diseases, Keck School of Medicine at USC, Los Angeles, California.
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
authors.affiliation: Minneapolis Veterans Affairs Medical Center Department of Medicine, University of Minnesota, Minneapolis.
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000472:pathogenicity*; D005075:Biological Evolution; D024881:Drug Resistance, Bacterial; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D037521:Virulence Factors
keywords: antimicrobial resistance; antimicrobial targets; antivirulence therapy; microbiome; resistance selection; virulence factors