Multi-omics based characterization of antibiotic response in clinical isogenic isolates of methicillin-susceptible/-resistantStaphylococcus aureus
- 주제(기타) Chemistry, Multidisciplinary
- 설명문(일반) [Jo, Sung-Hyun; Park, Han-Gyu; Lee, Jae-Seung; Jeon, Hyo-Jin; Kim, Yun-Gon] Soongsil Univ, Coll Engn, Dept Chem Engn, 369 Sangdo Ro, Seoul 06978, South Korea; [Song, Won-Suk] Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 08826, South Korea; [Lee, Yeon-Hee; Joo, Hwang-Soo] Duksung Womens Univ, Dept Biotechnol, Seoul 01369, South Korea; [Kim, Wooseong] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea; [Yang, Yung-Hun] Konkuk Univ, Dept Microbial Engn, Coll Engn, Seoul 05029, South Korea; [Kim, Jae-Seok] Hallym Univ, Kangdong Sacred Heart Hosp, Dept Lab Med, Coll Med, Seoul 05355, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 ROYAL SOC CHEMISTRY
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000174565
- 본문언어 영어
- Published As http://dx.doi.org/10.1039/d0ra05407k
- PubMed https://pubmed.ncbi.nlm.nih.gov/35516943
초록/요약
As demands for new antibiotics and strategies to control methicillin-resistantStaphylococcus aureus(MRSA) increase, there have been efforts to obtain more accurate and abundant information about the mechanism of the bacterial responses to antibiotics. However, most of the previous studies have investigated responses to antibiotics without considering the genetic differences between MRSA and methicillin-susceptibleS. aureus(MSSA). Here, we initially applied a multi-omics approach into the clinical isolates (i.e.,S. aureusWKZ-1 (MSSA) andS. aureusWKZ-2 (MRSA)) that are isogenic except for the mobile genetic element called staphylococcal cassette chromosomemec(SCCmec) type IV to explore the response to beta-lactam antibiotics (oxacillin). First, the isogenic pair showed a similar metabolism without oxacillin treatment. The quantitative proteomics demonstrated that proteins involved in peptidoglycan biosynthesis (MurZ, PBP2, SgtB, PrsA), two-component systems (VrsSR, WalR, SaeSR, AgrA), oxidative stress (MsrA1, MsrB), and stringent response (RelQ) were differentially regulated after the oxacillin treatment of the isogenic isolates. In addition, targeted metabolic profiling showed that metabolites belonging to the building blocks (lysine, glutamine, acetyl-CoA, UTP) of peptidoglycan biosynthesis machinery were specifically decreased in the oxacillin-treated MRSA. These results indicate that the difference in metabolism of this isogenic pair with oxacillin treatment could be caused only by SCCmectype IV. Understanding and investigating the antibiotic response at the molecular level can, therefore, provide insight into drug resistance mechanisms and new opportunities for antibiotics development.
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