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Pregled bibliografske jedinice broj: 587549

Ribosomal A site binding pattern differs between Arm methyltransferases from clinical pathogens and a natural producer of aminoglycosides


Obranić, Sonja; Babić, Fedora; Maravić Vlahoviček, Gordana
Ribosomal A site binding pattern differs between Arm methyltransferases from clinical pathogens and a natural producer of aminoglycosides // FEBS3+ meeting: From molecules to life and back Book of Abstracts / Dumić, Jerka ; Kovarik, Zrinka ; Varljen, Jadranka (ur.).
Rijeka: Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2012. str. 174-174 (poster, međunarodna recenzija, sažetak, znanstveni)


CROSBI ID: 587549 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Ribosomal A site binding pattern differs between Arm methyltransferases from clinical pathogens and a natural producer of aminoglycosides

Autori
Obranić, Sonja ; Babić, Fedora ; Maravić Vlahoviček, Gordana

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

Izvornik
FEBS3+ meeting: From molecules to life and back Book of Abstracts / Dumić, Jerka ; Kovarik, Zrinka ; Varljen, Jadranka - Rijeka : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2012, 174-174

ISBN
978-953-95551-4-4

Skup
FEBS3+ meeting: From molecules to life and back

Mjesto i datum
Opatija, Hrvatska, 13.06.2012. - 16.06.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
ribosomal antibiotics; microbial resistance; rRNA methyltransferases

Sažetak
One of the self-protecting systems that evolved within the aminoglycoside-producing bacteria was the employment of enzymes that add a methyl group to specific ribonucleotides in antibiotic-binding sites of the ribosome, thereby disrupting the antibiotic binding. In our previous research we have extensively studied biochemical and functional properties of one such enzyme, Sgm methyltransferase from the natural producer of aminoglycoside G-52 (6-N-methyl-sisomicin), Micromonospora zionensis, that belongs to the Arm (aminoglycoside resistance methyltransferase) family of enzymes. Recently, members of Arm family of enzymes were found to be spreading by horizontal transfer in growing number of clinical strains, which poses a serious threat for the successful treatment of severe bacterial infections. In this work, we compared the ribosomal A site binding pattern of the Sgm methyltransferase from the natural producer of aminoglycosides, with the Arm members isolated from clinical pathogens, RmtA, RmtB, RmtC and RmtD. We used a specialized E. coli system, in which all rrn operons were inactivated, and ribosomal RNA was transcribed from a vector-based rrn operon. We constructed single nucleotide mutations in the part of the operon corresponding to the A site of 16S rRNA. We determined generation time and investigated the ability of these cells to grow in the presence of various concentrations of aminoglycoside kanamycin. We then introduced actively expressing Arm methyltransferases into these cells and monitored the impact of the mutations on the enzyme activity by determining minimal inhibitory concentration of kanamycin and analyzing the target nucleotide methylation with primer extension. Our results show that the recognition motif of Arm enzymes on the bacterial ribosome differs for the Sgm enzyme versus the enzymes from clinical pathogens. Our data confirm that the Arm enzymes from clinical isolates can efficiently methylate the target nucleotide despite the individual A site mutations. However, Sgm methyltransferase cannot methylate the target nucleotide for some of the mutations introduced. This suggests that even though Arm enzymes from clinical strains and a natural producer of aminoglycosides methylate the same target nucleotide, thereby causing high-level aminoglycoside resistance, their mode of action is slightly different. In order to successfully fight the aminoglycoside resistance, it is therefore of great importance to analyze these differences in more detail and consider them for the design of effective inhibitors that would block the action of all the members of Arm family.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Farmacija



POVEZANOST RADA


Projekti:
006-0982913-1219 - Molekularne osnove djelovanja antibiotika i mehanizmi bakterijske rezistencije (Maravić Vlahoviček, Gordana, MZOS ) ( CroRIS)

Ustanove:
Farmaceutsko-biokemijski fakultet, Zagreb


Citiraj ovu publikaciju:

Obranić, Sonja; Babić, Fedora; Maravić Vlahoviček, Gordana
Ribosomal A site binding pattern differs between Arm methyltransferases from clinical pathogens and a natural producer of aminoglycosides // FEBS3+ meeting: From molecules to life and back Book of Abstracts / Dumić, Jerka ; Kovarik, Zrinka ; Varljen, Jadranka (ur.).
Rijeka: Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2012. str. 174-174 (poster, međunarodna recenzija, sažetak, znanstveni)
Obranić, S., Babić, F. & Maravić Vlahoviček, G. (2012) Ribosomal A site binding pattern differs between Arm methyltransferases from clinical pathogens and a natural producer of aminoglycosides. U: Dumić, J., Kovarik, Z. & Varljen, J. (ur.)FEBS3+ meeting: From molecules to life and back Book of Abstracts.
@article{article, author = {Obrani\'{c}, Sonja and Babi\'{c}, Fedora and Maravi\'{c} Vlahovi\v{c}ek, Gordana}, year = {2012}, pages = {174-174}, keywords = {ribosomal antibiotics, microbial resistance, rRNA methyltransferases}, isbn = {978-953-95551-4-4}, title = {Ribosomal A site binding pattern differs between Arm methyltransferases from clinical pathogens and a natural producer of aminoglycosides}, keyword = {ribosomal antibiotics, microbial resistance, rRNA methyltransferases}, publisher = {Hrvatsko dru\v{s}tvo za biokemiju i molekularnu biologiju (HDBMB)}, publisherplace = {Opatija, Hrvatska} }
@article{article, author = {Obrani\'{c}, Sonja and Babi\'{c}, Fedora and Maravi\'{c} Vlahovi\v{c}ek, Gordana}, year = {2012}, pages = {174-174}, keywords = {ribosomal antibiotics, microbial resistance, rRNA methyltransferases}, isbn = {978-953-95551-4-4}, title = {Ribosomal A site binding pattern differs between Arm methyltransferases from clinical pathogens and a natural producer of aminoglycosides}, keyword = {ribosomal antibiotics, microbial resistance, rRNA methyltransferases}, publisher = {Hrvatsko dru\v{s}tvo za biokemiju i molekularnu biologiju (HDBMB)}, publisherplace = {Opatija, Hrvatska} }




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