title: Single amino acid substitution Gly186Val in AdeS restores tigecycline susceptibility of Acinetobacter baumannii.
abstract: Amino acid substitutions within the AdeRS two-component system are believed to result in overexpression of the AdeABC efflux pump and extensive resistance to antibiotics in clinical Acinetobacter baumannii isolates. However, the exact amino acid substitutions in AdeRS that cause overexpression of the AdeABC efflux pump remain unclear. We elucidated the role of amino acid substitutions in AdeRS by a complementation assay in an adeRS knockout strain of A. baumannii.
  
  
  
  Five types of adeRS operon from tigecycline-resistant XDR A. baumannii (XDRAB) were cloned and introduced into the adeRS knockout strain to reverse its tigecycline susceptibility.
  
  
  
  Through shuffling gene segments among those five adeRS operons and performing site-directed mutagenesis, we found that the specific amino acid substitution Gly186Val in AdeS is crucial for reducing tigecycline susceptibility of A. baumannii.
  
  
  
  Our result demonstrates that a critical amino acid substitution in AdeS alters the AdeABC efflux pump-mediated tigecycline resistance of A. baumannii.
authors: Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors: Jun-Ren
authors: JR
authors: Sun
authors: University Center for Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan, Republic of China Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan 701, Taiwan, Republic of China.
authors: Wen-Yih
authors: WY
authors: Jeng
authors: Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China Graduate Institute of Pathology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors: Cherng-Lih
authors: CL
authors: Perng
authors: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors: Ya-Sung
authors: YS
authors: Yang
authors: Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien, Taiwan, Republic of China.
authors: Po-Chi
authors: PC
authors: Soo
authors: Graduate Institute of Pathology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors: Yen-Sen
authors: YS
authors: Chiang
authors: Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China drche0523@gmail.com.
authors: Tzong-Shi
authors: TS
authors: Chiueh
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics*; D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D032621:DNA Shuffling; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D026901:Membrane Transport Proteins / Q000235:genetics*; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D000078304:Tigecycline; D008911:Minocycline