Single amino acid substitution Gly186Val in AdeS restores tigecycline susceptibility of Acinetobacter baumannii

Jun Ren Sun, Wen-Yih Jeng, Cherng Lih Perng, Ya Sung Yang, Po Chi Soo, Yen Sen Chiang, Tzong Shi Chiueh

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusions: Our result demonstrates that a critical amino acid substitution in AdeS alters the AdeABC efflux pump-mediated tigecycline resistance of A. baumannii.

Original languageEnglish
Pages (from-to)1488-1492
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number6
DOIs
Publication statusPublished - 2016 Jun 13

Fingerprint

Acinetobacter baumannii
Amino Acid Substitution
Operon
Microbial Drug Resistance
Site-Directed Mutagenesis
tigecycline
Genes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Sun, Jun Ren ; Jeng, Wen-Yih ; Perng, Cherng Lih ; Yang, Ya Sung ; Soo, Po Chi ; Chiang, Yen Sen ; Chiueh, Tzong Shi. / Single amino acid substitution Gly186Val in AdeS restores tigecycline susceptibility of Acinetobacter baumannii. In: Journal of Antimicrobial Chemotherapy. 2016 ; Vol. 71, No. 6. pp. 1488-1492.
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Single amino acid substitution Gly186Val in AdeS restores tigecycline susceptibility of Acinetobacter baumannii. / Sun, Jun Ren; Jeng, Wen-Yih; Perng, Cherng Lih; Yang, Ya Sung; Soo, Po Chi; Chiang, Yen Sen; Chiueh, Tzong Shi.

In: Journal of Antimicrobial Chemotherapy, Vol. 71, No. 6, 13.06.2016, p. 1488-1492.

Research output: Contribution to journalArticle

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AU - Sun, Jun Ren

AU - Jeng, Wen-Yih

AU - Perng, Cherng Lih

AU - Yang, Ya Sung

AU - Soo, Po Chi

AU - Chiang, Yen Sen

AU - Chiueh, Tzong Shi

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Y1 - 2016/6/13

N2 - Objectives: 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. Methods: 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. Results: 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. Conclusions: Our result demonstrates that a critical amino acid substitution in AdeS alters the AdeABC efflux pump-mediated tigecycline resistance of A. baumannii.

AB - Objectives: 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. Methods: 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. Results: 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. Conclusions: Our result demonstrates that a critical amino acid substitution in AdeS alters the AdeABC efflux pump-mediated tigecycline resistance of A. baumannii.

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