Abstract: Tigecycline is one of the last choices to treat multidrug-resistant Klebsiella pneumoniae infection. However, the emergence of the tigecycline-resistant Klebsiella pneumoniae has posed a serious threat in clinical treatment. A clinical tigecycline-resistant Klebsiella pneumoniae strain was isolated, and a tigecycline-resistant plasmid was obtained by electroporation. Functional analysis revealed that two frameshift mutations occurred in the tet(A) gene on this plasmid. The antimicobial susceptibility tests indicated that the mutations could increase the minimal inhibition concentrations of tigecycline by 8 folds, whlie the MIC values of minocycline and tetracycline could increase 128 times due to these point mutations. The study confirmed that the plasmid-mediated tet(A) variant could confer the resistance to tigcycline in Klebsiella pneumoniae, which not only broaded the theoretical understanding about the resistance mechanism of Klebsiella pneumoniae to tigecycline, but also provided a basis to control the spread of such resistant gene among the gram-negative organisms.

Key words: tigecycline, Klebsiella pneumoniae, tet(A) mutation, resistance mechanism