Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii

Okada, Ui; Yamashita, Eiki; Neuberger, Arthur; Morimoto, Masaharu; Veen, Hendrik W. van; Murakami, Satoshi

doi:10.1038/s41467-017-01399-2

Cited by 89 publications

(113 citation statements)

References 60 publications

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“…From the ABC efflux pump superfamily, the genes A1S_0536 and A1S_1535 were selected. These genes encode permeases from the only two thus-far-identified ABC transporters involved in antimicrobial resistance, and both have been identified in strain ATCC 17978 (17,18). In addition, by analyzing the annotated genome of the same A. baumannii strain, several genes annotated as possible permeases of ABC transporters were identified.…”

Section: Resultsmentioning

confidence: 99%

Roles of Efflux Pumps from Different Superfamilies in the Surface-Associated Motility and Virulence of Acinetobacter baumannii ATCC 17978

Pérez-Varela

Corral

Aranda

et al. 2019

Antimicrob Agents Chemother

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Although the relationship between Acinetobacter baumannii efflux pumps and antimicrobial resistance is well documented, less is known about the involvement of these proteins in the pathogenicity of this nosocomial pathogen. In previous work, we identified the AbaQ major facilitator superfamily (MFS) efflux pump and demonstrated its participation in the motility and virulence of A. baumannii. In the present study, we examined the role in these processes of A. baumannii transporters belonging to different superfamilies of efflux pumps. Genes encoding known or putative permeases belonging to efflux pump superfamilies other than the MFS were selected, and the corresponding knockouts were constructed. The antimicrobial susceptibilities of these mutants were consistent with previously reported data. In mutants of A. baumannii strain ATCC 17978 carrying inactivated genes encoding the efflux pumps A1S_2736 (resistance nodulation division [RND]), A1S_3371 (multidrug and toxic compound extrusion [MATE]), and A1S_0710 (small multidrug resistance [SMR]), as well as the newly described ATP-binding cassette (ABC) permeases A1S_1242 and A1S_2622, both surface-associated motility and virulence were reduced compared to the parental strain. However, inactivation of the genes encoding the known ABC permeases A1S_0536 and A1S_1535, the newly identified putative ABC permeases A1S_0027 and A1S_1057, or the proteobacterial antimicrobial compound efflux (PACE) transporters A1S_1503 and A1S_2063 had no effects on bacterial motility or virulence. Our results demonstrate the involvement of antimicrobial transporters belonging at least to five of the six known efflux pump superfamilies in both surface-associated motility and virulence in A. baumannii ATCC 17978.

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Section: Resultsmentioning

confidence: 99%

Roles of Efflux Pumps from Different Superfamilies in the Surface-Associated Motility and Virulence of Acinetobacter baumannii ATCC 17978

Pérez-Varela

Corral

Aranda

et al. 2019

Antimicrob Agents Chemother

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“…The ABC transporter ATP-binding protein gene expression was increased by 6-fold in the eravacycline induced ATCC19606 strain when compared with the uninduced strain; however, the MacB protein subunit was under-expressed with a negative 2-fold change in the same strain. The MacA-MacB-TolC is a three protein efflux system that expels out mainly macrolide class of antibiotics, and their expression may not be influenced in a large way by the eravacycline [61]. MATE family pumps are not much related to resistance towards the tetracycline class of drugs and basically confer resistance towards fluoroquinolones and imipenems [62].…”

Section: Degs As Resistance Determinantsmentioning

confidence: 99%

Integrative analysis of outer membrane vesicles proteomics and whole-cell transcriptome analysis of eravacycline induced Acinetobacter baumannii strains

Kesavan

Vasudevan

et al. 2020

BMC Microbiol

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Background: Acinetobacter baumannii is a multidrug-resistant (MDR) hazardous bacterium with very high antimicrobial resistance profiles. Outer membrane vesicles (OMVs) help directly and/or indirectly towards antibiotic resistance in these organisms. The present study aims to look on the proteomic profile of OMV as well as on the bacterial transcriptome upon exposure and induction with eravacycline, a new synthetic fluorocycline. RNA sequencing analysis of whole-cell and LC-MS/MS proteomic profiling of OMV proteome abundance were done to identify the differential expression among the eravacycline-induced A. baumannii ATCC 19606 and A. baumannii clinical strain JU0126. Results: The differentially expressed genes from the RNA sequencing were analysed using R package and bioinformatics software and tools. Genes encoding drug efflux and membrane transport were upregulated among the DEGs from both ATCC 19606 and JU0126 strains. As evident with the induction of eravacycline resistance, ribosomal proteins were upregulated in both the strains in the transcriptome profiles and also resistance pumps, such as MFS, RND, MATE and ABC transporters. High expression of stress and survival proteins were predominant in the OMVs proteome with ribosomal proteins, chaperons, OMPs OmpA, Omp38 upregulated in ATCC 19606 strain and ribosomal proteins, toluene tolerance protein, siderophore receptor and peptidases in the JU0126 strain. The induction of resistance to eravacycline was supported by the presence of upregulation of ribosomal proteins, resistance-conferring factors and stress proteins in both the strains of A. baumannii ATCC 19606 and JU0126, with the whole-cell gene transcriptome towards both resistance and stress genes while the OMVs proteome enriched more with survival proteins.Conclusion: The induction of resistance to eravacycline in the strains were evident with the increased expression of ribosomal and transcription related genes/proteins. Apart from this resistance-conferring efflux pumps, outer membrane proteins and stress-related proteins were also an essential part of the upregulated DEGs. However, the expression profiles of OMVs proteome in the study was independent with respect to the whole-cell RNA expression profiles with low to no correlation. This indicates the possible role of OMVs to be more of back-up additional protection to the existing bacterial cell defence during the antibacterial stress.

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“…Unlike canonical ABC transporters, ABC3 members (also known as type VII ABC transporters) (33) are not proposed to transport substrates across the membrane in which they are embedded. At present, MacB, a toxin and antibiotic transporter (33)(34)(35), is the only representative of the ABC3 superfamily to be structurally characterized (33,(36)(37)(38). Each monomer of the MacB homodimer has a distinctive four-transmembrane helix topology and an N-terminally fused nucleotide binding domain.…”

Section: Significancementioning

confidence: 99%

Insights into bacterial lipoprotein trafficking from a structure of LolA bound to the LolC periplasmic domain

Kaplan

Greene

Crow

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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In Gram-negative bacteria, outer-membrane lipoproteins are essential for maintaining cellular integrity, transporting nutrients, establishing infections, and promoting the formation of biofilms. The LolCDE ABC transporter, LolA chaperone, and LolB outer-membrane receptor form an essential system for transporting newly matured lipoproteins from the outer leaflet of the cytoplasmic membrane to the innermost leaflet of the outer membrane. Here, we present a crystal structure of LolA in complex with the periplasmic domain of LolC. The structure reveals how a solvent-exposed β-hairpin loop (termed the "Hook") and trio of surface residues (the "Pad") of LolC are essential for recruiting LolA from the periplasm and priming it to receive lipoproteins. Experiments with purified LolCDE complex demonstrate that association with LolA is independent of nucleotide binding and hydrolysis, and homology models based on the MacB ABC transporter predict that LolA recruitment takes place at a periplasmic site located at least 50 Å from the inner membrane. Implications for the mechanism of lipoprotein extraction and transfer are discussed. The LolA-LolC structure provides atomic details on a key protein interaction within the Lol pathway and constitutes a vital step toward the complete molecular understanding of this important system.

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Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii

Cited by 89 publications

References 60 publications

Roles of Efflux Pumps from Different Superfamilies in the Surface-Associated Motility and Virulence of Acinetobacter baumannii ATCC 17978

Roles of Efflux Pumps from Different Superfamilies in the Surface-Associated Motility and Virulence of Acinetobacter baumannii ATCC 17978

Integrative analysis of outer membrane vesicles proteomics and whole-cell transcriptome analysis of eravacycline induced Acinetobacter baumannii strains

Insights into bacterial lipoprotein trafficking from a structure of LolA bound to the LolC periplasmic domain

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