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  3. Comparison of antibacterial activities and resistance mechanisms of omadacycline and tigecycline against Enterococcus faecium

Comparison of antibacterial activities and resistance mechanisms of omadacycline and tigecycline against Enterococcus faecium

  • J Antibiot (Tokyo). 2022 Aug;75(8):463-471. doi: 10.1038/s41429-022-00538-2.
Xiaoming Liu  # 1 2,  Chaoqin Zhang  # 3 4,  Yuxi Zhao  # 3 4,  Hang Cheng  # 3 4,  Yu Wang 3 4,  Zhanwen Wang 3 4,  Yongpeng Shang 3 4,  Jinxin Zheng 3 4,  Zhijian Yu 5 6,  Yiyi Shi 7 8
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, 518067, China.
  • 2 Department of Gastroenterology, Shenzhen Shekou People's Hospital, Shenzhen, 518067, China.
  • 3 Department of Infectious Diseases and the Key Lab of Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China.
  • 4 Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518052, China.
  • 5 Department of Infectious Diseases and the Key Lab of Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China. yuzhijiansmu@163.com.
  • 6 Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518052, China. yuzhijiansmu@163.com.
  • 7 Department of Infectious Diseases and the Key Lab of Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China. shiyiyi_93@163.com.
  • 8 Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518052, China. shiyiyi_93@163.com.
  • # Contributed equally.
PMID: 35760902 DOI: 10.1038/s41429-022-00538-2
Abstract

This study aims to compare the antimicrobial activity of omadacycline with tigecycline against clinical isolates of Enterococcus faecium and investigate their resistance mechanisms. Non-duplicate clinical E. faecium isolates (n = 224) were collected and the minimal inhibitory concentrations (MICs) of omadacycline and tigecycline were determined by broth microdilution method. The tet genes and the genetic mutations in 16 S rRNA genes and 30 S ribosomal protein S10 were determined by PCR and sequence alignment. The global protein abundances of the omadacycline-induced and parent isolates were determined by a Q Exactive plus mass spectrometer. The MIC50/MIC90 of omadacycline and tigecycline against the 224 E. faecium isolates were 0.25/0.5 mg l-1 and 0.125/0.25 mg l-1, respectively. Among these E. faecium isolates, the frequency of the isolates with omadacycline MICs ≥ 0.25 mg l-1 were significantly higher than that with tigecycline MICs ≥ 0.25 mg l-1. Moreover, the T1473C and/or G1468A mutations in the 16 S rRNA and Lys98Glu mutation in the 30 S ribosomal protein S10 were identified in the 3 series of tigecycline or omadacycline- nonsusceptible isolates selected in vitro. The abundances of 32 proteins changed in the omadacycline-induced isolate, of which 10 increased and 22 decreased. The abundance of tet(M) increased significantly in the omadacycline-induced isolate, and the abundance of proteins included in cellular process and metabolic process decreased. In conclusion, Omadacycline and tigecycline exhibits excellent activities against clinical isolates of E. faecium and exposure to omadacycline and tigecycline can result in significant cross-resistance to both Antibiotics. The high-level expression of tet(M) in E. faecium may confer resistance to omadacycline.

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