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REVIEW] 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
J. Microbiol. 2019;57(3):185-194.   Published online February 26, 2019
DOI: https://doi.org/10.1007/s12275-019-8520-1
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  • 9 Web of Science
  • 7 Crossref
AbstractAbstract
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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MINIREVIEW] Multidrug efflux pumps in Staphylococcus aureus and their clinical implications
Soojin Jang
J. Microbiol. 2016;54(1):1-8.   Published online January 5, 2016
DOI: https://doi.org/10.1007/s12275-016-5159-z
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  • 0 Download
  • 78 Crossref
AbstractAbstract
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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MINIREVIEW] 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
J. Microbiol. 2015;53(6):355-364.   Published online May 30, 2015
DOI: https://doi.org/10.1007/s12275-015-5248-4
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AbstractAbstract
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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  • 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
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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
Seunghwa Lee , Saemee Song , Minho Lee , Soonhye Hwang , Ji-Sun Kim , Nam-Chul Ha , Kangseok Lee
J. Microbiol. 2014;52(2):148-153.   Published online February 1, 2014
DOI: https://doi.org/10.1007/s12275-014-3578-2
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AbstractAbstract
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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    Yue Gong, Rui Hong Guo, Joon Haeng Rhee, Young Ran Kim
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    Inseong Jo, Jin-Sik Kim, Yongbin Xu, Jaekyung Hyun, Kangseok Lee, Nam-Chul Ha
    Journal of Microbiology.2019; 57(3): 185.     CrossRef
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  • 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
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    Seunghwa Lee, Saemee Song, Kangseok Lee
    Current Microbiology.2014; 68(6): 729.     CrossRef

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