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      Screening system for xenosiderophores as potential drug delivery agents in mycobacteria.

      1 ,
      Antimicrobial agents and chemotherapy
      American Society for Microbiology

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          Abstract

          In order to establish a screening system for xenosiderophores which can be utilized by mycobacteria, we generated a set of mutants of Mycobacterium smegmatis that are blocked in different steps of the well-known iron acquisition system. One mutant with a block in mycobactin biosynthesis was generated from strain mc(2)155 by chemical mutagenesis. The exochelin biosynthesis gene fxbA and the ferric exochelin uptake gene fxuA, previously identified by Fiss et al. (E. H. Fiss, S. Yu, and W. R. Jacobs, Jr., Mol. Microbiol. 14:557-559, 1994), were knocked out by gene replacement. Adjacent chromosomal fragments were used for homologous recombination in order to replace wild-type genes by the kanamycin resistance gene from transposon Tn903. Gene replacement was confirmed by PCR. The isolated mutants show the expected phenotype: fxbA mutants are defective in exochelin biosynthesis, whereas fxuA mutants excrete a significantly larger amount of exochelin compared to the amount excreted by the parent strain. This is due to their defectiveness in ferriexochelin uptake, as demonstrated in growth promotion assays. This new set of mutants allows differentiation of siderophores that supply mycobacteria with iron by ligand exchange with exochelin or mycobactin, by the use of separate siderophore uptake routes, or by the use of the exochelin permease. All these types of iron uptake routes were identified with 25 exogenous siderophores as test substances. Siderophores that act without ligand exchange are potential candidates as drug vectors that can be used to overcome permeability-mediated resistance.

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          Author and article information

          Journal
          Antimicrob Agents Chemother
          Antimicrobial agents and chemotherapy
          American Society for Microbiology
          0066-4804
          0066-4804
          May 2001
          : 45
          : 5
          Affiliations
          [1 ] Department of Infection Biology, Hans-Knöll-Institut für Naturstoff-Forschung e.V., D-07708 Jena, Germany.
          Article
          10.1128/AAC.45.5.1317-1322.2001
          90468
          11302790
          29176e0f-8b9e-40c4-9f31-c4510b72eac0
          History

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