Pregled bibliografske jedinice broj: 600870
Sgm methyltransferase exhibits a unique ribosomal A site binding pattern among Arm family of enzymes.
Sgm methyltransferase exhibits a unique ribosomal A site binding pattern among Arm family of enzymes. // 5th Croatian Congress of Microbiology with International participation Book of Abstracts / Černi, Silvija ; Šeruga Musić, Martina ; Škorić, Dijana (ur.).
Zagreb: Hrvatsko mikrobiološko društvo, 2012. str. 68-68 (poster, domaća recenzija, sažetak, znanstveni)
CROSBI ID: 600870 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Sgm methyltransferase exhibits a unique ribosomal A site binding pattern among Arm family of enzymes.
Autori
Obranić, Sonja ; Babić, Fedora ; Maravić Vlahoviček, Gordana
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
5th Croatian Congress of Microbiology with International participation Book of Abstracts
/ Černi, Silvija ; Šeruga Musić, Martina ; Škorić, Dijana - Zagreb : Hrvatsko mikrobiološko društvo, 2012, 68-68
ISBN
978-953-7778-05-7
Skup
5th Croatian Congress of Microbiology with International participation
Mjesto i datum
Primošten, Hrvatska, 26.09.2012. - 30.09.2012
Vrsta sudjelovanja
Poster
Vrsta recenzije
Domaća recenzija
Ključne riječi
aminoglycoside resistance; methyltransferases; Arm; Kam; Ribosome; A site; mutagenesis
Sažetak
Sgm methyltransferase was isolated from the natural producer of aminoglycoside antibiotic G-52 (6-N-methyl-sisomicin), Micromonospora zionensis. This enzyme is a member of Arm family of enzymes and modifies nucleotide G1405 in the A site of 16S rRNA, causing highlevel resistance to aminoglycoside antibiotics. Recently, members of Arm family of enzymes were found to be spreading by horizontal transfer in growing number of clinical strains, which significantly reduces the odds of a successful treatment of various bacterial infections. In this work, we explored the ribosomal A site binding pattern of the Sgm methyltransferase from the natural producer of aminoglycosides and the Arm enzymes isolated from clinical pathogens, ArmA, RmtA, RmtB, RmtC and RmtD. In our experiments we introduced various 16S rRNA mutations in E. coli strain carrying only one copy of 16S rRNA gene. Those cells had a uniform population of mutated ribosomes. We 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 methyltransferase activity by determining minimal inhibitory concentration of kanamycin for these cells and analyzing the target nucleotide methylation with primer extension. Our results indicate that the mutations introduced in the A site of 16S rRNA affect the interaction between aminoglycoside resistance methyltransferase Sgm and bacterial ribosome. However, Arm methyltransferases isolated from clinical pathogens do not show the same ribosomal binding pattern, which suggests that Sgm methyltransferase exhibits a unique ribosomal A site binding pattern among Arm enzymes. So even though Arm enzymes from clinical strains and natural producer of aminoglycosides methylate the same target nucleotide, thereby causing high-level aminoglycoside resistance, their mode of action is slightly different. It is therefore of great importance to functionally characterize more members of the family in order to construct effective inhibitors of the members of the whole Arm family, thus fighting aminoglycoside resistance.
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