TY - JOUR
T1 - Functional and phylogenetic analysis of TetX variants to design a new classification system
AU - Cheng, Qipeng
AU - Cheung, Yanchu
AU - Liu, Chenyu
AU - Chan, Edward Wai Chi
AU - Wong, Kwok Yin
AU - Zhang, Rong
AU - Chen, Sheng
N1 - Funding Information:
The work was supported by the Guangdong Major Project of Basic and Applied Basic Research (2020B0301030005) and NSFC/RGC grant (N_CityU521/18).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/5
Y1 - 2022/5
N2 - Recently, many TetX variants such as Tet(X3~14) were reported to confer resistance to tigecycline which is a last-resort antibiotic used to treat infections caused by multidrug-resistant bacteria. In this study, we identified essential residues including 329, 339, 340, 350, and 351 in TetX variants that mediated the evolution of the tigecycline-inactive Tet(X2) enzyme to the active forms of Tet(X3) and Tet(X4). Based on their amino acid sequences and functional features, we classified TetX variants into TetX-A class, TetX-B class and TetX-C class. We further found that TetX-A class variants originated from Bacteroidetes, with some variants further evolving to TetX-C class and acquired by Enterobacteriaceae. On the other hand, our data showed that some variants genes belonging to TetX-A class evolved directly to TetX-B class, which was further transmitted to Acinetobacter spp. This new classification system may facilitate better clinical management of patients infected by TetX-producing strains.
AB - Recently, many TetX variants such as Tet(X3~14) were reported to confer resistance to tigecycline which is a last-resort antibiotic used to treat infections caused by multidrug-resistant bacteria. In this study, we identified essential residues including 329, 339, 340, 350, and 351 in TetX variants that mediated the evolution of the tigecycline-inactive Tet(X2) enzyme to the active forms of Tet(X3) and Tet(X4). Based on their amino acid sequences and functional features, we classified TetX variants into TetX-A class, TetX-B class and TetX-C class. We further found that TetX-A class variants originated from Bacteroidetes, with some variants further evolving to TetX-C class and acquired by Enterobacteriaceae. On the other hand, our data showed that some variants genes belonging to TetX-A class evolved directly to TetX-B class, which was further transmitted to Acinetobacter spp. This new classification system may facilitate better clinical management of patients infected by TetX-producing strains.
UR - http://www.scopus.com/inward/record.url?scp=85130983152&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-03465-y
DO - 10.1038/s42003-022-03465-y
M3 - Journal article
C2 - 35641548
AN - SCOPUS:85130983152
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 522
ER -