<p>Among the last-resort antibiotics, tigecycline is a semisynthetic drug derivative of tetracycline used in medical facilities, resulting in tigecycline-resistant <i>Acinetobacter baumannii</i> (TRAB) strain development. Recent reports suggested the emergence of heteroresistance, intermediate-resistance, and resistance strain development against the tigecycline of <i>A. baumannii</i> isolates, causing treatment failure in healthcare facilities. In this study, we developed tigecycline-resistant (AbTGC-R) mutants through experimental evolution to investigate the development of moderate resistance in <i>A. baumannii</i> with the reference strain ATCC19606. Clonal populations derived from the evolved lines demonstrated ~ 20-fold resistance against tigecycline. Evolution of resistance against tigecycline did not accompany fitness cost or impact on adherence to abiotic substratum and biofilm-forming potential. The mutants demonstrated cross-resistance against erythromycin and azithromycin. Whole genome sequencing analysis identified mutations in a number of genes, of which adenosine deaminase encoding <i>add2</i>, and a SAM-dependent methyltransferase encoding <i>gstcD</i> (alias <i>trm</i>) were determined to be associated with moderate tigecycline resistance.</p>

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Resistance associated genomic variations for moderate level tigecycline resistance evolution in Acinetobacter baumannii

  • Kusumita Acharya,
  • Shatarupa Biswas,
  • Sayani Bhattacharyya,
  • Mallika Ghosh,
  • Arijit Bhattacharya

摘要

Among the last-resort antibiotics, tigecycline is a semisynthetic drug derivative of tetracycline used in medical facilities, resulting in tigecycline-resistant Acinetobacter baumannii (TRAB) strain development. Recent reports suggested the emergence of heteroresistance, intermediate-resistance, and resistance strain development against the tigecycline of A. baumannii isolates, causing treatment failure in healthcare facilities. In this study, we developed tigecycline-resistant (AbTGC-R) mutants through experimental evolution to investigate the development of moderate resistance in A. baumannii with the reference strain ATCC19606. Clonal populations derived from the evolved lines demonstrated ~ 20-fold resistance against tigecycline. Evolution of resistance against tigecycline did not accompany fitness cost or impact on adherence to abiotic substratum and biofilm-forming potential. The mutants demonstrated cross-resistance against erythromycin and azithromycin. Whole genome sequencing analysis identified mutations in a number of genes, of which adenosine deaminase encoding add2, and a SAM-dependent methyltransferase encoding gstcD (alias trm) were determined to be associated with moderate tigecycline resistance.