Reviews
- REVIEW] Recent paradigm shift in the assembly of bacterial tripartite efflux pumps and the type I secretion system
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Inseong Jo , Jin-Sik Kim , Yongbin Xu , Jaekyung Hyun , Kangseok Lee , Nam-Chul Ha
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J. Microbiol. 2019;57(3):185-194. Published online February 26, 2019
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DOI: https://doi.org/10.1007/s12275-019-8520-1
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44
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9
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7
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Abstract
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Tripartite efflux pumps and the type I secretion system of
Gram-negative bacteria are large protein complexes that span
the entire cell envelope. These complexes expel antibiotics and
other toxic substances or transport protein toxins from bacterial
cells. Elucidating the binary and ternary complex structures
at an atomic resolution are crucial to understanding the
assembly and working mechanism. Recent advances in cryoelectron
microscopy along with the construction of chimeric
proteins drastically shifted the assembly models. In this review,
we describe the current assembly models from a historical
perspective and emphasize the common assembly mechanism
for the assembly of diverse tripartite pumps and type
I secretion systems.
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Citations
Citations to this article as recorded by

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- MINIREVIEW] Multidrug efflux pumps in Staphylococcus aureus and their clinical implications
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Soojin Jang
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J. Microbiol. 2016;54(1):1-8. Published online January 5, 2016
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DOI: https://doi.org/10.1007/s12275-016-5159-z
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47
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0
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78
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Abstract
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Antibiotic resistance is rapidly spreading among bacteria
such as Staphylococcus aureus, an opportunistic bacterial
pathogen that causes a variety of diseases in humans. For
the last two decades, bacterial multidrug efflux pumps have
drawn attention due to their potential association with clinical
multidrug resistance. Numerous researchers have demonstrated
efflux-mediated resistance in vitro and in vivo
and found novel multidrug transporters using advanced
genomic information about bacteria. This article aims to
provide a concise summary of multidrug efflux pumps and
their important clinical implications, focusing on recent
findings concerning S. aureus efflux pumps.
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Citations
Citations to this article as recorded by

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Manuel Alcalde-Rico, Sara Hernando-Amado, Paula Blanco, José L. Martínez
Frontiers in Microbiology.2016;[Epub] CrossRef
- MINIREVIEW] Molecular architecture of the bacterial tripartite multidrug efflux pump focusing on the adaptor bridging model
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Saemee Song , Jin-Sik Kim , Kangseok Lee , Nam-Chul Ha
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J. Microbiol. 2015;53(6):355-364. Published online May 30, 2015
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DOI: https://doi.org/10.1007/s12275-015-5248-4
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48
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Abstract
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Gram-negative bacteria expel a wide range of toxic substances
through tripartite drug efflux pumps consisting of an inner
membrane transporter, an outer membrane channel protein,
and a periplasmic adaptor protein. These pumps form tripartite
assemblies which can span the entire cell envelope,
including the inner and outer membranes. There have been
controversial findings regarding the assembly of the individual
components in tripartite drug efflux pumps. Recent
structural and functional studies have advanced our understanding
of the assembly and working mechanisms of the
pumps. Here, we re-evaluate the assembly models based on
recent structural and functional studies. In particular, this
study focuses on the ‘adaptor bridging model’, highlighting
the intermeshing cogwheel-like interactions between the tip
regions of the outer membrane channel protein and the periplasmic
adaptor protein in the hexameric assembly.
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Citations
Citations to this article as recorded by

- Structural Features and Energetics of the Periplasmic Entrance Opening of the Outer Membrane Channel TolC Revealed by Molecular Dynamics Simulation and Markov State Model Analysis
Jingwei Weng, Wenning Wang
Journal of Chemical Information and Modeling.2019; 59(5): 2359. CrossRef - Recent paradigm shift in the assembly of bacterial tripartite efflux pumps and the type I secretion system
Inseong Jo, Jin-Sik Kim, Yongbin Xu, Jaekyung Hyun, Kangseok Lee, Nam-Chul Ha
Journal of Microbiology.2019; 57(3): 185. CrossRef - Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?
Ronald Domalaon, Temilolu Idowu, George G. Zhanel, Frank Schweizer
Clinical Microbiology Reviews.2018;[Epub] CrossRef - Genetic identification of factors for extracellular cellulose accumulation in the thermophilic cyanobacterium Thermosynechococcus vulcanus: proposal of a novel tripartite secretion system
Kaisei Maeda, Jyunya Tamura, Yukiko Okuda, Rei Narikawa, Takafumi Midorikawa, Masahiko Ikeuchi
Molecular Microbiology.2018; 109(1): 121. CrossRef - Switch Loop Flexibility Affects Substrate Transport of the AcrB Efflux Pump
Reinke T. Müller, Timothy Travers, Hi-jea Cha, Joshua L. Phillips, S. Gnanakaran, Klaas M. Pos
Journal of Molecular Biology.2017; 429(24): 3863. CrossRef - Molecular Rationale behind the Differential Substrate Specificity of Bacterial RND Multi-Drug Transporters
Venkata Krishnan Ramaswamy, Attilio V. Vargiu, Giuliano Malloci, Jürg Dreier, Paolo Ruggerone
Scientific Reports.2017;[Epub] CrossRef - Structure of the MacAB–TolC ABC-type tripartite multidrug efflux pump
Anthony W. P. Fitzpatrick, Salomé Llabrés, Arthur Neuberger, James N. Blaza, Xiao-Chen Bai, Ui Okada, Satoshi Murakami, Hendrik W. van Veen, Ulrich Zachariae, Sjors H. W. Scheres, Ben F. Luisi, Dijun Du
Nature Microbiology.2017;[Epub] CrossRef - Structural Basis for the Serratia marcescens Lipase Secretion System: Crystal Structures of the Membrane Fusion Protein and Nucleotide-Binding Domain
Daichi Murata, Hiroyuki Okano, Clement Angkawidjaja, Masato Akutsu, Shun-ichi Tanaka, Kenyu Kitahara, Takuya Yoshizawa, Hiroyoshi Matsumura, Yuji Kado, Eiichi Mizohata, Tsuyoshi Inoue, Satoshi Sano, Yuichi Koga, Shigenori Kanaya, Kazufumi Takano
Biochemistry.2017; 56(47): 6281. CrossRef - The Crystal Structure of the YknZ Extracellular Domain of ABC Transporter YknWXYZ from Bacillus amyloliquefaciens
Yongbin Xu, Jianyun Guo, Lulu Wang, Rui Jiang, Xiaoling Jin, Jing Liu, Shengdi Fan, Chun-Shan Quan, Nam-Chul Ha, Bostjan Kobe
PLOS ONE.2016; 11(5): e0155846. CrossRef
Research Support, Non-U.S. Gov't
- Interaction between the α-Barrel Tip of Vibrio vulnificus TolC Homologs and AcrA Implies the Adapter Bridging Model
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Seunghwa Lee , Saemee Song , Minho Lee , Soonhye Hwang , Ji-Sun Kim , Nam-Chul Ha , Kangseok Lee
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J. Microbiol. 2014;52(2):148-153. Published online February 1, 2014
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DOI: https://doi.org/10.1007/s12275-014-3578-2
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46
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10
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Abstract
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The AcrAB-TolC multidrug efflux pump confers resistance to Escherichia coli against many antibiotics and toxic compounds. The TolC protein is an outer membrane factor that participates in the formation of type I secretion systems. The genome of Vibrio vulnificus encodes two proteins homologous to the E. coli TolC, designated TolCV1 and TolCV2. Here, we show that both TolCV1 and TolCV2 partially complement the E. coli TolC function and physically interact with the membrane fusion protein AcrA, a component of the E. coli AcrAB-TolC efflux pump. Using site-directed mutational analyses and an in vivo cross-linking assay, we demonstrated that the α-barrel tip region of TolC homologs plays a critical role in the formation of functional AcrAB-TolC efflux pumps. Our findings suggest the adapter bridging model as a general assembly mechanism for tripartite drug efflux pumps in Gram-negative bacteria.
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Citations
Citations to this article as recorded by

- Progress of Antimicrobial Mechanisms of Stilbenoids
Xiancai Li, Yongqing Li, Binghong Xiong, Shengxiang Qiu
Pharmaceutics.2024; 16(5): 663. CrossRef - Membrane Efflux Pumps of Pathogenic Vibrio Species: Role in Antimicrobial Resistance and Virulence
Jerusha Stephen, Manjusha Lekshmi, Parvathi Ammini, Sanath H. Kumar, Manuel F. Varela
Microorganisms.2022; 10(2): 382. CrossRef - TolCV1 Has Multifaceted Roles During Vibrio vulnificus Infection
Yue Gong, Rui Hong Guo, Joon Haeng Rhee, Young Ran Kim
Frontiers in Cellular and Infection Microbiology.2021;[Epub] CrossRef - Recent paradigm shift in the assembly of bacterial tripartite efflux pumps and the type I secretion system
Inseong Jo, Jin-Sik Kim, Yongbin Xu, Jaekyung Hyun, Kangseok Lee, Nam-Chul Ha
Journal of Microbiology.2019; 57(3): 185. CrossRef - NaCl promotes antibiotic resistance by reducing redox states in Vibrio alginolyticus
Jun Yang, Zao‐Hai Zeng, Man‐Jun Yang, Zhi‐Xue Cheng, Xuan‐Xian Peng, Hui Li
Environmental Microbiology.2018; 20(11): 4022. CrossRef - ATP-Binding Cassette Transporter VcaM from Vibrio cholerae is Dependent on the Outer Membrane Factor Family for Its Function
Wen-Jung Lu, Hsuan-Ju Lin, Thamarai Janganan, Cheng-Yi Li, Wei-Chiang Chin, Vassiliy Bavro, Hong-Ting Lin
International Journal of Molecular Sciences.2018; 19(4): 1000. CrossRef - Functional analysis of Vibrio vulnificus RND efflux pumps homologous to Vibrio cholerae VexAB and VexCD, and to Escherichia coli AcrAB
Seunghwa Lee, Ji-Hyun Yeom, Sojin Seo, Minho Lee, Sarang Kim, Jeehyeon Bae, Kangseok Lee, Jihwan Hwang
Journal of Microbiology.2015; 53(4): 256. CrossRef - Molecular architecture of the bacterial tripartite multidrug efflux pump focusing on the adaptor bridging model
Saemee Song, Jin-Sik Kim, Kangseok Lee, Nam-Chul Ha
Journal of Microbiology.2015; 53(6): 355. CrossRef - Interaction Mediated by the Putative Tip Regions of MdsA and MdsC in the Formation of a Salmonella-Specific Tripartite Efflux Pump
Saemee Song, Soonhye Hwang, Seunghwa Lee, Nam-Chul Ha, Kangseok Lee, Eric Cascales
PLoS ONE.2014; 9(6): e100881. CrossRef - Functional Analysis of TolC Homologs in Vibrio vulnificus
Seunghwa Lee, Saemee Song, Kangseok Lee
Current Microbiology.2014; 68(6): 729. CrossRef