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

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.