title: Antimicrobial activity of picolinic acid against extracellular and intracellular Mycobacterium avium complex and its combined activity with clarithromycin, rifampicin and fluoroquinolones.
abstract: OBJECTIVE
  A natural metal ion chelator, picolinic acid (PA), is known to potentiate macrophage antimycobacterial activity. Here, we studied the antimicrobial activity of PA against extracellular and intramacrophage Mycobacterium avium complex (MAC) organisms.
  
  
  METHODS
  MAC organisms, MAC-infected macrophages or MAC-infected type II pneumocytes were cultured in the presence or absence of PA with or without antimycobacterial drugs, and residual bacterial cfu of extracellular or intracellular MAC were counted on 7H11 agar plates.
  
  
  RESULTS
  First, PA exhibited antimicrobial activity against extracellular and intramacrophage MAC. The effect of PA was mimicked by other metal ion-chelating agents, such as ethylenediamine tetraacetic acid and O,O'-bis (2-aminophenyl) ethyleneglycol-N,N,N',N'-tetraacetic acid. Second, PA potentiated antimicrobial effects of a two-drug combination of clarithromycin/rifampicin and some fluoroquinolones (levofloxacin, sitafloxacin and gatifloxacin) against extracellular and intramacrophage MAC. Similar combined effects of PA with clarithromycin/rifampicin were also seen in the case of MAC residing within type II alveolar epithelial cells.
  
  
  CONCLUSIONS
  PA exerted an appreciable anti-MAC activity, when used singly or in combination with some antimycobacterial drugs (clarithromycin/rifampicin and fluoroquinolones), suggesting the usefulness of PA as an adjunct for clinical antimicrobial chemotherapy of MAC infections.
authors.affiliation: Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Cai
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Sato
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Seiko
authors.initials: S
authors.lastname: Yamabe
authors.forename: Miho
authors.initials: M
authors.lastname: Hiraki
authors.forename: Chiaki
authors.initials: C
authors.lastname: Sano
authors.forename: Haruaki
authors.initials: H
authors.lastname: Tomioka
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D017291:Clarithromycin / Q000494:pharmacology; D004357:Drug Synergism; D004847:Epithelial Cells / Q000382:microbiology*; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000254:growth & development; D010848:Picolinic Acids / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000382:microbiology*; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D010848:Picolinic Acids; D017291:Clarithromycin; C030614:picolinic acid; D012293:Rifampin