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Indigenous and acquired modifications in the aminoglycoside binding sites of Pseudomonas aeruginosa rRNAs

Investigación publicada en RNA Biology

1 de agosto de 2013

Aminoglycoside antibiotics remain the drugs of choice for treatment of Pseudomonas aeruginosa infections, particularly for respiratory complications in cystic-fibrosis patients. Previous studies on other bacteria have shown that aminoglycosides have their primary target within the decoding region of 16S rRNA helix 44 with a secondary target in 23S rRNA helix 69. Here, we have mapped P. aeruginosa rRNAs using MALDI mass spectrometry and reverse transcriptase primer extension to identify nucleotide modifications that could influence aminoglycoside interactions. Helices 44 and 45 contain indigenous (housekeeping) modifications at m ( 4) Cm1402, m ( 3) U1498, m ( 2) G1516, m ( 6) 2A1518, and m ( 6) 2A1519; helix 69 is modified at m ( 3) Ψ1915, with m ( 5) U1939 and m ( 5) C1962 modification in adjacent sequences. All modifications were close to stoichiometric, with the exception of m ( 3) Ψ1915, where about 80% of rRNA molecules were methylated. The modification status of a virulent clinical strain expressing the acquired methyltransferase RmtD was altered in two important respects: RmtD stoichiometrically modified m ( 7) G1405 conferring high resistance to the aminoglycoside tobramycin and, in doing so, impeded one of the methylation reactions at C1402. Mapping the nucleotide methylations in P. aeruginosa rRNAs is an essential step toward understanding the architecture of the aminoglycoside binding sites and the rational design of improved drugs against this bacterial pathogen




Gutierrez B., Douthwaite S. y Gonzalez-Zorn B..




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Indigenous and acquired modifications in the aminoglycoside binding sites of Pseudomonas aeruginosa rRNAs

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Indigenous and acquired modifications in the aminoglycoside binding sites of Pseudomonas aeruginosa rRNAs


Participantes:

Universidad ComplutenseDepartamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM).

Universidad ComplutenseServicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

University of Southern DenmarkDepartment of Biochemistry and Molecular Biology. University of Southern Denmark (SDU).







FACTOR YEAR Q
5.377 2013

NLMID: 101235328

PMID: 23948732

ISSN: 1547-6286



TÍTULO: Indigenous and acquired modifications in the aminoglycoside binding sites of Pseudomonas aeruginosa rRNAs


REVISTA: RNA Biol


NUMERACIÓN: 10(8):1324-32


AÑO: 2013


EDITORIAL: Georgetown, TX : Landes Bioscience


AUTORES: Gutierrez B., Douthwaite S. and Gonzalez-Zorn B..


PARTICIPANTES VISAVET


Bruno González Zorn

DOI: https://doi.org/10.4161/rna.25984


CITA ESTA PUBLICACIÓN:

Gutierrez B., Douthwaite S. y Gonzalez-Zorn B. Indigenous and acquired modifications in the aminoglycoside binding sites of Pseudomonas aeruginosa rRNAs. RNA Biology. 10(8):1324-32. 2013. (A). ISSN: 1547-6286. DOI: 10.4161/rna.25984


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