title: 16S rRNA methyltransferase KsgA contributes to oxidative stress resistance and virulence in Staphylococcus aureus.
abstract: We previously reported that the rRNA methyltransferases RsmI and RsmH, which are responsible for cytidine dimethylation at position 1402 of 16S rRNA in the decoding center of the ribosome, contribute to Staphylococcus aureus virulence. Here we evaluated other 16S rRNA methyltransferases, including KsgA (RsmA), RsmB/F, RsmC, RsmD, RsmE, and RsmG. Knockout of KsgA, which methylates two adjacent adenosines at positions 1518 and 1519 of 16S rRNA in the intersubunit bridge of the ribosome, attenuated the S. aureus killing ability against silkworms. The ksgA knockout strain was sensitive to oxidative stress and had a lower survival rate in murine macrophages than the parent strain. The ksgA knockout strain exhibited decreased translational fidelity in oxidative stress conditions. Administration of N-acetyl-l-cysteine, a free-radical scavenger, restored the killing ability of the ksgA knockout strain against silkworms. These findings suggest that the methyl-modifications of 16S rRNA by KsgA contribute to maintain ribosome function under oxidative conditions and thus to S. aureus virulence.
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kyuma
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Kizaki
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ryuno
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan. Electronic address: kaito@mol.f.u-tokyo.ac.jp.
authors.forename: Chikara
authors.initials: C
authors.lastname: Kaito
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D012831:Bombyx / Q000254:growth & development / Q000382:microbiology; D055786:Gene Knockout Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000254:growth & development / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D050296:Microbial Viability; D018384:Oxidative Stress; D010587:Phagocytosis; D014176:Protein Biosynthesis; D000067996:RAW 264.7 Cells; D012323:RNA Processing, Post-Transcriptional; D012329:RNA, Bacterial / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D007527:Isoenzymes; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D008780:Methyltransferases; C047346:16S rRNA (adenine(1518)-N(6)-adenine(1519)-N(6))-dimethyltransferase; D000241:Adenosine; D000111:Acetylcysteine
keywords: 16S rRNA; Intersubunit bridge; Oxidative stress; Staphylococcus aureus; rRNA methyl modifications