title: An evolved oxazolidinone with selective potency against Mycobacterium tuberculosis and gram positive bacteria.
abstract: Innovation of new antibacterials that are effective against strains that have developed resistance to existing drugs would strengthen our ability to treat and subsequently control spread of pathogenic bacteria. Increasing incidence of infections with drug resistant bacteria has become a common occurrence in recent times. We have developed an evolved oxazolidinone, T145, which inhibits growth of Enterococcus faecalis, Staphylococcus aureus and Mycobacterium tuberculosis (Mtb) with sub μg/ml potencies that are potentially therapeutically valuable. The oxazolidinone is bactericidal against Mtb but bacteriostatic against E. faecalis and S. aureus. In addition to therapeutically valuable potency and bactericidal activity against Mtb, T145 minimizes selection of spontaneous resistant mutants, a trait that prolongs longevity of a drug in clinical use.
authors.affiliation: Taskforce to Study Resistance Emergence & Antimicrobial Development Technology and Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, 1550 Orleans St, Baltimore, MD 21287, United States.
authors.forename: Amit
authors.initials: A
authors.lastname: Kaushik
authors.affiliation: Department of Chemistry, University of St. Thomas, St. Paul, MN 55105, United States.
authors.forename: Abigail M
authors.initials: AM
authors.lastname: Heuer
authors.affiliation: Taskforce to Study Resistance Emergence & Antimicrobial Development Technology and Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, 1550 Orleans St, Baltimore, MD 21287, United States.
authors.forename: Drew T
authors.initials: DT
authors.lastname: Bell
authors.affiliation: Department of Chemistry, University of St. Thomas, St. Paul, MN 55105, United States.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Culhane
authors.affiliation: Department of Chemistry, University of St. Thomas, St. Paul, MN 55105, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Ebner
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, United States.
authors.forename: Nicole
authors.initials: N
authors.lastname: Parrish
authors.affiliation: Department of Chemistry, University of St. Thomas, St. Paul, MN 55105, United States. Electronic address: jtippoliti@stthomas.edu.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Ippoliti
authors.affiliation: Taskforce to Study Resistance Emergence & Antimicrobial Development Technology and Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, 1550 Orleans St, Baltimore, MD 21287, United States. Electronic address: lamichhane@jhu.edu.
authors.forename: Gyanu
authors.initials: G
authors.lastname: Lamichhane
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones
keywords: Antimicrobials; E. faecalis; Mycobacterium tuberculosis; Oxazolidinone; Staphylococcus aureus