Emergence of a (M) Variant Conferring Resistance to Tigecycline in .

The aim of this study was to gain insight into the resistance determinants conferring resistance to tigecycline in (.) and to investigate the genetic elements involved in their horizontal transfer. A total of 31 tetracycline-resistant isolates were screened for tigecycline resistance by broth microdilution. isolate SC128 was subjected to whole genome sequencing with particular reference to resistance determinants involved in tigecycline resistance. Transferability of genomic island (GI) GISC128 was investigated by transformation. The roles of (L) or (M) in contributing to tigecycline resistance in were confirmed by transformation using different (L)- or (M)-carrying constructs. Only SC128 showed a tigecycline resistance phenotype. A (L)-(M) and co-carrying GISC128 was identified in this isolate. After transfer of the novel GI into a susceptible recipient, this recipient showed the same tigecycline resistance phenotype. Further transfer experiments with specific (L)- or (M)-carrying constructs confirmed that only (M), but not (L), contributes to resistance to tigecycline. Protein sequence analysis identified a Tet(M) variant, which is responsible for tigecycline resistance in SC128. It displayed 94.8% amino acid identity with the reference Tet(M) of DO plasmid 1. To the best of our knowledge, this is the first time that a (M) variant conferring resistance to tigecycline was identified in . Its location on a GI will accelerate its transmission among the population.