Naslov
The aminoglycoside resistance methyltransferase Sgm impedes RsmF methylation at an adjacent rRNA nucleotide in the ribosomal A site

Autori
Čubrilo, Sonja ; Babić, Fedora ; Douthwaite, Stephen ; Maravić Vlahoviček, Gordana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Book of Abstracts / Maravić Vlahoviček, Gordana - Zagreb : Hrvatsko mikrobiološko društvo, 2009, 61-61

ISBN
978-953-96567-9-3

Skup
Central European Symposium on Antimicrobial Resistance

Mjesto i datum
Zadar, Hrvatska, 23.09.2009. - 26.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
aminoglycoside antibiotics; 16S rRNA methylation; methyltransferase Sgm
(amioglycoside antibiotics; bacterial resistance; methyltransferase Sgm)

Sažetak
Sgm methyltransferase is a member of the Arm family of enzymes that confer resistance to aminoglycoside antibiotics by modifying the ribosomal RNA within the binding site of the aminoglycosides, the A site of the ribosome. The Sgm enzyme was isolated from sisomicin producing actinomycete Micromonospora zionensis, where it protects the cell from the toxic effect of the antibiotic. Recently, some new members of this family have emerged in clinical practice, posing a serious threat to the successful treatment of various bacterial infections with the aminoglycosides. Therefore, there is a great need for the functional characterisation of these enzymes. In all kingdoms of life, a series of covalent modifications in ribosomal RNA is needed for the proper assembly of the ribosome. In bacteria, the most common type of rRNA modification is the methylation of the base, followed by the methylation at the 2’ -O-position of the ribose and the conversion of uridine to pseuouridine. Each indigenous rRNA methylation in bacteria is carried out by its own specific housekeeping methyltransferase. It is therefore interesting how an extra methylation conferring antibiotic resistance can be exerted within a heavily modified rRNA region. In this work we show that the Sgm methyltransferase confers resistance to 4, 6-disubstituted deoxystreptamine aminoglycosides by introducing the 16S rRNA modification m7G1405 within the ribosomal A site. In the vicinity of the nucleotide G1405 there are several nucleotides methylated by housekeeping methyltransferases, such as m4Cm1402 and m5C1407. We also show that the modification at m5C1407 by the methyltransferase RsmF is impeded as Sgm gains access to its adjacent G1405 target on the 30S ribosomal subunit. Our data indicate that methyltransferases that cause antibiotic resistance due to the methylation of the functionally important region of rRNA could affect the indigenous rRNA methylation caused by housekeeping methyltransferases and thus play an important role in determining resistance levels.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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