title: Novel anti-infection agents: small-molecule inhibitors of bacterial transcription factors.
abstract: Structure-based drug design was utilized to identify potent small-molecule inhibitors of proteins within the AraC family of bacterial transcription factors, which control virulence in medically important microbes. These agents represent a novel approach to fight infectious disease and may be less likely to promote resistance development. These compounds lack intrinsic antibacterial activity in vitro and were able to limit a bacterial infection in a mouse model of urinary tract infection.
authors.affiliation: Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA. tbowser@paratekpharm.com
authors.forename: Todd E
authors.initials: TE
authors.lastname: Bowser
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Bartlett
authors.forename: Mark C
authors.initials: MC
authors.lastname: Grier
authors.forename: Atul K
authors.initials: AK
authors.lastname: Verma
authors.forename: Taduesz
authors.initials: T
authors.lastname: Warchol
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Levy
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alekshun
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D004755:Enterobacteriaceae / Q000187:drug effects; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D014157:Transcription Factors; D004247:DNA