TY - JOUR
T1 - Cryo-EM structure and complementary drug efflux activity of the Acinetobacter baumannii multidrug efflux pump AdeG
AU - Ouyang, Zhenlin
AU - He, Wenbo
AU - Wu, Di
AU - An, Hao
AU - Duan, Lei
AU - Jiao, Min
AU - He, Xiaoyu
AU - Yu, Qinyue
AU - Zhang, Jiaxin
AU - Qin, Qian
AU - Wang, Ruochen
AU - Zheng, Fang
AU - Hwang, Peter M.
AU - Hua, Xiaoting
AU - Zhu, Li
AU - Wen, Yurong
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2025/3/6
Y1 - 2025/3/6
N2 - Multidrug-resistant Acinetobacter baumannii has emerged as one of the most antibiotic-resistant bacterial pathogens associated with nosocomial infection, with its resistance highly depending on multiple multidrug efflux pumps. Here, we report the cryoelectron microscopy (cryo-EM) structure of Acinetobacter drug efflux G (AdeG), the inner membrane component of one of three important resistance-nodulation-cell division (RND) pump family members in A. baumannii, which is involved in drug resistance to chloramphenicol, trimethoprim, ciprofloxacin, and clindamycin. We systematically compare the structures and substrate binding specificities of AdeG, AdeB, and AdeJ multidrug efflux pumps via molecular docking, revealing potential determinants for drug binding. Knockout experiments demonstrate a functional complementarity between AdeABC, AdeFGH, and AdeIJK. Our study provides a structural understanding of A. baumannii multidrug efflux pump AdeG and reveals complementary drug efflux activity between AdeG and other RND efflux pumps, which may promote further rational drug discovery efforts targeting multidrug efflux pumps.
AB - Multidrug-resistant Acinetobacter baumannii has emerged as one of the most antibiotic-resistant bacterial pathogens associated with nosocomial infection, with its resistance highly depending on multiple multidrug efflux pumps. Here, we report the cryoelectron microscopy (cryo-EM) structure of Acinetobacter drug efflux G (AdeG), the inner membrane component of one of three important resistance-nodulation-cell division (RND) pump family members in A. baumannii, which is involved in drug resistance to chloramphenicol, trimethoprim, ciprofloxacin, and clindamycin. We systematically compare the structures and substrate binding specificities of AdeG, AdeB, and AdeJ multidrug efflux pumps via molecular docking, revealing potential determinants for drug binding. Knockout experiments demonstrate a functional complementarity between AdeABC, AdeFGH, and AdeIJK. Our study provides a structural understanding of A. baumannii multidrug efflux pump AdeG and reveals complementary drug efflux activity between AdeG and other RND efflux pumps, which may promote further rational drug discovery efforts targeting multidrug efflux pumps.
KW - Acinetobacter baumannii
KW - AdeG
KW - cryoelectron microscopy
KW - efflux pump
KW - multidrug resistance
UR - https://www.scopus.com/pages/publications/85217120277
U2 - 10.1016/j.str.2024.12.009
DO - 10.1016/j.str.2024.12.009
M3 - 文章
C2 - 39798571
AN - SCOPUS:85217120277
SN - 0969-2126
VL - 33
SP - 539-551.e4
JO - Structure
JF - Structure
IS - 3
ER -