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mikrobiologie@vetmed.fu-berlin.de
The emergence of various genes mediating tigecycline resistance poses a significant risk to public health safety. Since the description of tet(X4), which was located on a plasmid and mediated high-level resistance to tigecycline, numerous studies have been conducted on tigecycline resistance. In previous reports, tet(A) variants have been considered to mediate low-level resistance to tigecycline, which received much less attention in clinical research. In this study, we found a greatly high rate (62.1%, 998/1,607) of tet(A) variants carriage in 1,607 carbapenem-resistant Klebsiella pneumoniae isolates from Henan Province, China. Moreover, we confirmed that high-level tigecycline resistance could be rapidly produced by the amplification of tet(A) variants in these isolates. The amplification and overexpression of tet(A) variants were verified by the determination of gene copy numbers and qRT-PCR. Through the analysis of the raw sequencing data and the plasmid mapping depth, we found that the ∆tnpA homologous sequence of Tn1721 supports the amplification of the region that harbors the tet(A) variants and forms a large number of repeat arrays through translocatable units (TUs). Moreover, the epidemiological analysis of tet(A) variant-carrying structures among 1,607 clinical carbapenem-resistant Klebsiella pneumoniae isolates indicated that the TU structure formed by the homologous sequence ∆tnpA is widely present. These results indicated that the presence of tigecycline resistance-mediating tet(A) variants in this clinical pathogen represents a greater health concern than initially thought and should be monitored consistently.