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Antibiotics 2016, 5(2), 17; doi:10.3390/antibiotics5020017

The Oligopeptide Permease Opp Mediates Illicit Transport of the Bacterial P-site Decoding Inhibitor GE81112

1
Laboratory of Genetics, University of Camerino, via Gentile III da Varano, Camerino 62032 (MC), Italy
2
NAICONS Scrl, Viale Ortles 22/4, Milano 20139, Italy
Dedicated to the fond memory of Knud H. Nierhaus (April 7, 1941–April 7, 2016), a distinguished scientist, a dear colleague, a sincere friend.
Work carried out in partial fulfilment of the requirements for a Doctoral thesis, University of Camerino, Camerino 62032, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Christopher C. Butler
Received: 20 March 2016 / Revised: 10 May 2016 / Accepted: 12 May 2016 / Published: 24 May 2016
(This article belongs to the Special Issue Inhibitors of the Translational Apparatus)
View Full-Text   |   Download PDF [1611 KB, uploaded 24 May 2016]   |  

Abstract

GE81112 is a tetrapeptide antibiotic that binds to the 30S ribosomal subunit and specifically inhibits P-site decoding of the mRNA initiation codon by the fMet-tRNA anticodon. GE81112 displays excellent microbiological activity against some Gram-positive and Gram-negative bacteria in both minimal and complete, chemically defined, broth, but is essentially inactive in complete complex media. This is due to the presence of peptides that compete with the antibiotic for the oligopeptide permease system (Opp) responsible for its illicit transport into the bacterial cells as demonstrated in the cases of Escherichia coli and Bacillus subtilis. Mutations that inactivate the Opp system and confer GE81112 resistance arise spontaneously with a frequency of ca. 1 × 10−6, similar to that of the mutants resistant to tri-l-ornithine, a known Opp substrate. On the contrary, cells expressing extrachromosomal copies of the opp genes are extremely sensitive to GE81112 in rich medium and GE81112-resistant mutations affecting the molecular target of the antibiotic were not detected upon examining >109 cells of this type. However, some mutations introduced in the 16S rRNA to confer kasugamycin resistance were found to reduce the sensitivity of the cells to GE81112. View Full-Text
Keywords: peptide antibiotic; MIC; translation inhibitors; peptide transport; antibiotic resistance; cross resistance peptide antibiotic; MIC; translation inhibitors; peptide transport; antibiotic resistance; cross resistance
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MDPI and ACS Style

Maio, A.; Brandi, L.; Donadio, S.; Gualerzi, C.O. The Oligopeptide Permease Opp Mediates Illicit Transport of the Bacterial P-site Decoding Inhibitor GE81112. Antibiotics 2016, 5, 17.

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