Analysis of rILERS, an isoleucyl-tRNA synthetase gene associated with mupirocin production by Pseudomonas fluorescens NCIMB 10586.

Some strains of Pseudomonas fluorescens produce the antibiotic mupirocin, which functions as a competitive inhibitor of isoleucyl-tRNA synthetase (ILERS). Mupirocin-producing strains of P. fluorescens must overcome the inhibitory effects of the antibiotic to avoid self-suicide. However, it is not clear how P. fluorescens protects itself from the toxic effects of mupirocin. In this report, we describe a second gene encoding isoleucyl-tRNA synthetase (rILERS) in P. fluorescens that is associated with the mupirocin biosynthetic gene cluster. Random mutagenesis of the mupirocin-producing strain, P. fluorescens 10586, resulted in a mupirocin-defective mutant disrupted in a region with similarity to ILERS, the target site for mupirocin. The ILERS gene described in the present study was sequenced and shown to be encoded by a 3093 bp ORF, which is 264 bp larger than the ILERS gene previously identified in P. fluorescens 10586. rILERS from P. fluorescens is most closely related to prokaryotic or eukaryotic sources of ILERS that are resistant to mupirocin. Interestingly, the relatedness between rILERS and the ILERS previously described in P. fluorescens 10586 was low (24% similarity), which indicates that P. fluorescens contains two isoforms of isoleucyl-tRNA synthetase.

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