강유리 (성균관대학교 의과대학, 삼성서울병원)

한빛사논문

조회507

성균관대학교 의과대학, 삼성서울병원

CV File 169 kb

Int. J. Antimicrob. Agents, Sep 14 2023, S0924-8579(23)00250-9 | https://doi.org/10.1016/j.ijantimicag.2023.106971 Genetic alterations in methicillin-susceptible Staphylococcus aureus associated with high vancomycin minimum inhibitory concentration.

Yu Ri Kang ^1,2, Doo Ryeon Chung ^1,2,3, Jae-Hoon Ko ¹, Kyungmin Huh ^1,2, Sun Young Cho ^1,3, Cheol-In Kang¹, Kyong Ran Peck ¹

¹Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

²Asia Pacific Foundation for Infectious Diseases (APFID), Seoul, Republic of Korea

³Center for Infection Prevention and Control, Samsung Medical Center, Seoul, Republic of Korea

Corresponding author: Doo Ryeon Chung, M.D., Ph.D.

Abstract

Background: There are many reports on gene mutations observed in methicillin-resistant Staphylococcus aureus (MRSA) showing reduced susceptibility to vancomycin. However, there are limited studies on the genetic alterations that contribute to high vancomycin minimum inhibitory concentration (MIC) in methicillin-susceptible S. aureus (MSSA). This study aimed to compare MSSA strains with high vancomycin MIC to those with low MIC and identify specific genetic alterations associated with increased vancomycin MIC.

Methods: We analyzed 124 MSSA strains, with 62 having vancomycin MICs of 1-2 mg/l (MS-HV) and the remaining 62 having MIC < 1 mg/l (MS-LV) as control. PCR amplification and sequencing were conducted to identify point mutations and amino acid changes in the vraSR, graRS, and walRK operons and rpoB gene. We compared the number of single nucleotide polymorphisms (SNPs) and specific mutations in the indicated gene between the two groups.

Results: MS-HV had a significantly higher median number of SNPs in studied genes than MS-LV (5 vs. 3; P < 0.0001), with higher frequency of SNPs in graR and walK genes. MS-HV also displayed a significantly higher prevalence of specific mutations in graR (V135I, I136V, and V136I) compared to MS-LV. Odds of having a high vancomycin MIC was 5.54 times higher in strains with a mutation in graR, and 5.32 times higher in strains with a mutation in walK, compared to those without these mutations.

Conclusions: Mutations in graR and walK genes may contribute to reduced vancomycin susceptibility in MSSA. Our study gives key insights into the mechanisms underlying this phenomenon.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-20)
연구진국내 연구진
분야 의약학 > 감염의학

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