DOCSLIB.ORG

The Lyse Superfamily: Topology of the Lysine Exporter Lyse of Corynebacterium Glutamicum, a Paradyme for a Novel Superfamily of Transmembrane Solute Translocators

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Lyse Superfamily: Topology of the Lysine Exporter Lyse of Corynebacterium Glutamicum, a Paradyme for a Novel Superfamily of Transmembrane Solute Translocators J. Mol. Microbiol. Biotechnol. (1999) 1(2): 327-336. Topology of LysE and aJMMB Novel Superfamily Research of Exporters Article 327 The LysE Superfamily: Topology of the Lysine Exporter LysE of Corynebacterium glutamicum, a Paradyme for a Novel Superfamily of Transmembrane Solute Translocators M. Vrljic1, J. Garg2, A. Bellmann1, S. Wachi2, thereby regulating the intracellular concentration of this R. Freudl1, M. J. Malecki2, H. Sahm1, amino acid. The need for this function is surprising as the V. J. Kozina2, L. Eggeling1*, and M. H. Saier Jr.2 L-lysine biosynthetic pathway in C. glutamicum, as in other bacteria, is strictly regulated (Nakayama, 1985; Eggeling, 1Institut für Biotechnologie, 1994). However, L-lysine export is essential in Forschungszentrum Jülich GmbH, environments containing peptides: in the presence of low 52428 Jülich, Germany concentrations of lysine-containing peptides and upon 2Department of Biology, deletion of the export carrier gene lysE, exceptionally high University of California at San Diego, cytoplasmic concentrations (>1M) of L-lysine build up La Jolla, CA 92093-0116, USA leading to bacteriostasis. The specific export function provided by LysE is also a prerequisite for the production of L-lysine with C. glutamicum, mutants of which are used Abstract for the production of about 3.5x105 tons of this amino acid per year (Leuchtenberger, 1996). LysE therefore provides In Corynebacterium glutamicum the LysE carrier a new function in regulating a cytoplasmic amino acid con- protein exhibits the unique function of exporting L- centration, and it is the first example of export as a target lysine. We here analyze the membrane topology of for the improvement of industrial amino acid production. LysE, a protein of 236 amino acyl residues, using In addition to the unique physiological function of LysE, PhoA- and LacZ-fusions. The amino-terminal end of its structure is unusual. The carrier consists of 236 amino LysE is located in the cytoplasm whereas the carboxy- acyl residues (Vrljic et al., 1996), and it exhibits six terminal end is found in the periplasm. Although 6 hydrophobic domains that could correspond to six hydrophobic domains were identified based on transmembrane helical spanners typical of many polytopic hydropathy analyses, only five transmembrane membrane transport proteins. LysE lacks significant spanning helices appear to be present. The additional sequence similarity to known export translocators which hydrophobic segment may dip into the membrane or are constituent members of the identified 12 families be surface localized. We show that LysE is a member catalyzing efflux of organic molecules and cations (Saier, of a family of proteins found, for example, in 1994; Saier et al., 1994; Paulsen et al., 1996). It therefore Escherichia coli, Bacillus subtilis, Mycobacterium represents a novel family of proteins distinct from all other tuberculosis and Helicobacter pylori. This family, which established families of transporters (Vrljic et al., 1996). The we have designated the LysE family, is distantly related current veritable flood of genome sequencing activities has to two additional protein families which we have resulted in the realization that numerous putative LysE designated the YahN and CadD families. These three homologues are encoded on bacterial chromosomes and families, the members of which exhibit similar sizes, plasmids. LysE evidently represents the tip of an iceberg hydropathy profiles, and sequence motifs comprise of a novel class of transporters which may exhibit unique the LysE superfamily. Functionally characterized physiological functions analogous to that of LysE. members of the LysE superfamily export L-lysine, In the present paper we report investigations into the cadmium and possibly quarternary amines. We membrane topology of LysE using the well established suggest that LysE superfamily members will prove to methodology of alkaline phosphatase and ß-galactosidase catalyze export of a variety of biologically important fusion constructions. Additionally, we searched the DNA solutes. and protein databases for the presence of LysE homologues. A thorough analysis revealed that LysE is a Introduction member of a novel superfamily of carriers that consists of three discrete families. The functionally characterized An unusual bacterial transport protein was recently members of this superfamily exclusively catalyze solute characterized biochemically, physiologically, and export. molecularly (Broer and Krämer, 1991; Vrljic et al., 1995; 1996). This carrier is LysE from the Gram-positive Results bacterium Corynebacterium glutamicum. It exports L-lysine, The LysE Family Currently sequenced members of the LysE family are Received January 29, 1999; revised April 27, 1999; accepted May 4, 1999. *For correspondence. Email [email protected]; presented in Table 1. The LysE protein of C. glutamicum is Tel. +49 2461 61 5132; Fax. +49 2461 61 2710. the only functionally characterized member of this family. © 1999 Horizon Scientific Press Further Reading Caister Academic Press is a leading academic publisher of advanced texts in microbiology, molecular biology and medical research. Full details of all our publications at caister.com • MALDI-TOF Mass Spectrometry in Microbiology Edited by: M Kostrzewa, S Schubert (2016) www.caister.com/malditof • Aspergillus and Penicillium in the Post-genomic Era Edited by: RP Vries, IB Gelber, MR Andersen (2016) www.caister.com/aspergillus2 • The Bacteriocins: Current Knowledge and Future Prospects Edited by: RL Dorit, SM Roy, MA Riley (2016) www.caister.com/bacteriocins • Omics in Plant Disease Resistance Edited by: V Bhadauria (2016) www.caister.com/opdr • Acidophiles: Life in Extremely Acidic Environments Edited by: R Quatrini, DB Johnson (2016) www.caister.com/acidophiles • Climate Change and Microbial Ecology: Current Research and Future Trends Edited by: J Marxsen (2016) www.caister.com/climate • Biofilms in Bioremediation: Current Research and Emerging Technologies • Flow Cytometry in Microbiology: Technology and Applications Edited by: G Lear (2016) www.caister.com/biorem Edited by: MG Wilkinson (2015) www.caister.com/flow • Microalgae: Current Research and Applications • Probiotics and Prebiotics: Current Research and Future Trends Edited by: MN Tsaloglou (2016) www.caister.com/microalgae Edited by: K Venema, AP Carmo (2015) www.caister.com/probiotics • Gas Plasma Sterilization in Microbiology: Theory, Applications, Pitfalls and New Perspectives • Epigenetics: Current Research and Emerging Trends Edited by: H Shintani, A Sakudo (2016) Edited by: BP Chadwick (2015) www.caister.com/gasplasma www.caister.com/epigenetics2015 • Virus Evolution: Current Research and Future Directions • Corynebacterium glutamicum: From Systems Biology to Biotechnological Applications Edited by: SC Weaver, M Denison, M Roossinck, et al. (2016) www.caister.com/virusevol Edited by: A Burkovski (2015) www.caister.com/cory2 • Arboviruses: Molecular Biology, Evolution and Control Edited by: N Vasilakis, DJ Gubler (2016) • Advanced Vaccine Research Methods for the Decade of www.caister.com/arbo Vaccines Edited by: F Bagnoli, R Rappuoli (2015) • Shigella: Molecular and Cellular Biology www.caister.com/vaccines Edited by: WD Picking, WL Picking (2016) www.caister.com/shigella • Antifungals: From Genomics to Resistance and the Development of Novel Agents • Aquatic Biofilms: Ecology, Water Quality and Wastewater Edited by: AT Coste, P Vandeputte (2015) Treatment www.caister.com/antifungals Edited by: AM Romaní, H Guasch, MD Balaguer (2016) www.caister.com/aquaticbiofilms • Bacteria-Plant Interactions: Advanced Research and Future Trends Edited by: J Murillo, BA Vinatzer, RW Jackson, et al. (2015) • Alphaviruses: Current Biology www.caister.com/bacteria-plant Edited by: S Mahalingam, L Herrero, B Herring (2016) www.caister.com/alpha • Aeromonas Edited by: J Graf (2015) • Thermophilic Microorganisms www.caister.com/aeromonas Edited by: F Li (2015) www.caister.com/thermophile • Antibiotics: Current Innovations and Future Trends Edited by: S Sánchez, AL Demain (2015) www.caister.com/antibiotics • Leishmania: Current Biology and Control Edited by: S Adak, R Datta (2015) www.caister.com/leish2 • Acanthamoeba: Biology and Pathogenesis (2nd edition) Author: NA Khan (2015) www.caister.com/acanthamoeba2 • Microarrays: Current Technology, Innovations and Applications Edited by: Z He (2014) www.caister.com/microarrays2 • Metagenomics of the Microbial Nitrogen Cycle: Theory, Methods and Applications Edited by: D Marco (2014) www.caister.com/n2 Order from caister.com/order 328 Vrljic et al. Table 1. Protein Members of the LysE Family Abbreviation Name or description in database Organism Size (no. residues) Database and accession no. LysE Cgl Lysine exporter protein Corynebacterium glutamicum 236 gbX96471 Orf1 Mtu* Hypothetical 20.9 KD protein CY20G9.14 Mycobacterium tuberculosis 212 spQ11154 Orf2 Mtu Hypothetical 20.8 KD protein CY39.33C Mycobacterium tuberculosis 199 spQ10871 YggA Eco Hypothetical 23.2 KD protein in SBM-FBA intergenic region Escherichia coli 211 spP11667 YggA Asa* Lysine export homologue Aeromonas salmonicida 206 gbU65741 YggA Ahy* YggA homologue gene product Aeromonas hydrophila 206 gbX89469 Orf Bsu Hypothetical protein YisU Bacillus subtilis 220 gbY09476 Orf Hpy Conserved hypothetical integral membrane protein Helicobacter pylori 210 gbAE000585 * Based on the DNA sequences; the amino acid sequences of these three proteins (used in the reported analyses) were modified
Load more

Recommended publications
  • Comparative Genomics and Functional Annotation of Bacterial Transporters
    Physics of Life Reviews 5 (2008) 22–49 www.elsevier.com/locate/plrev Review Comparative genomics and functional annotation of bacterial transporters Mikhail S. Gelfand a,b,∗, Dmitry A. Rodionov a,c a Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karetny pereulok 19, Moscow 127994, Russia b Department of Bioengineering and Bioinformatics, Moscow State University, Russia c Burnham Institute for Medical Research, La Jolla, CA 92037, USA Received 6 October 2007; received in revised form 8 October 2007; accepted 10 October 2007 Available online 24 October 2007 Communicated by M. Frank-Kamenetskii Abstract Transport proteins are difficult to study experimentally, and because of that their functional characterization trails that of en- zymes. The comparative genomic analysis is a powerful approach to functional annotation of proteins, which makes it possible to utilize the genomic sequence data from thousands of organisms. The use of computational techniques allows one to identify candidate transporters, predict their structure and localization in the membrane, and perform detailed functional annotation, which includes substrate specificity and cellular role. We overview the main techniques of analysis of transporters’ structure and function. We consider the most popular algorithms to identify transmembrane segments in protein sequences and to predict topology of multispanning proteins. We describe the main approaches of the comparative genomics, and how they may be applied to the analysis of transporters, and provide examples showing how combinations of these techniques is used for functional annotation of new transporter specificities in known families, characterization of new families, and prediction of novel transport mechanisms. © 2007 Elsevier B.V.
    [Show full text]
  • The Genome and Genetics of a High Oxidative Stress Tolerant Serratia Sp
    Vicente et al. BMC Genomics (2016) 17:301 DOI 10.1186/s12864-016-2626-1 RESEARCH ARTICLE Open Access The genome and genetics of a high oxidative stress tolerant Serratia sp. LCN16 isolated from the plant parasitic nematode Bursaphelenchus xylophilus Claudia S. L. Vicente1,2, Francisco X. Nascimento1, Yoriko Ikuyo2, Peter J. A. Cock3, Manuel Mota1,4 and Koichi Hasegawa2* Abstract Background: Pine wilt disease (PWD) is a worldwide threat to pine forests, and is caused by the pine wood nematode (PWN) Bursaphelenchus xylophilus. Bacteria are known to be associated with PWN and may have an important role in PWD. Serratia sp. LCN16 is a PWN-associated bacterium, highly resistant to oxidative stress in vitro, and which beneficially contributes to the PWN survival under these conditions. Oxidative stress is generated as a part of the basal defense mechanism used by plants to combat pathogenic invasion. Here, we studied the biology of Serratia sp. LCN16 through genome analyses, and further investigated, using reverse genetics, the role of two genes directly involved in the neutralization of H2O2,namelytheH2O2 transcriptional factor oxyR;andtheH2O2-targeting enzyme, catalase katA. Results: Serratia sp. LCN16 is phylogenetically most closely related to the phytosphere group of Serratia, which includes S. proteamaculans, S. grimessi and S. liquefaciens.Likewise,Serratia sp. LCN16 shares many features with endophytes (plant-associated bacteria), such as genes coding for plant polymer degrading enzymes, iron uptake/ transport, siderophore and phytohormone synthesis, aromatic compound degradation and detoxification enzymes. OxyR and KatA are directly involved in the high tolerance to H2O2 of Serratia sp. LCN16. Under oxidative stress, Serratia sp.
    [Show full text]
  • Helicobacter Pylori: Comparative Genomics and Structure-Function Analysis of the Flagellum Biogenesis Protein HP0958
    UCC Library and UCC researchers have made this item openly available. Please let us know how this has helped you. Thanks! Title Helicobacter pylori: comparative genomics and structure-function analysis of the flagellum biogenesis protein HP0958 Author(s) de Lacy Clancy, Ceara A. Publication date 2014 Original citation de Lacy Clancy, C. A. 2014. Helicobacter pylori: comparative genomics and structure-function analysis of the flagellum biogenesis protein HP0958. PhD Thesis, University College Cork. Type of publication Doctoral thesis Rights © 2014, Ceara A. De Lacy Clancy. http://creativecommons.org/licenses/by-nc-nd/3.0/ Item downloaded http://hdl.handle.net/10468/1684 from Downloaded on 2021-10-10T14:33:51Z Helicobacter pylori: Comparative genomics and structure-function analysis of the flagellum biogenesis protein HP0958 A Thesis Presented in Partial Fulfilment of the Requirements for the Degree of Doctor of Philosophy by Ceara de Lacy Clancy, B.Sc. School of Microbiology National University of Ireland, Cork Supervisor: Prof. Paul W. O’Toole Head of School of Microbiology: Prof. Gerald Fitzgerald February 2014 Table of Contents Table of Contents Abstract ........................................................................................................................ i Chapter 1 Literature Review....................................................................................................... 1 1 Helicobacter pylori .................................................................................................. 2 1.1 Discovery
    [Show full text]
  • Transport Capabilities of Eleven Gram-Positive Bacteria: Comparative Genomic Analyses
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1768 (2007) 1342–1366 www.elsevier.com/locate/bbamem Review Transport capabilities of eleven gram-positive bacteria: Comparative genomic analyses Graciela L. Lorca 1,2, Ravi D. Barabote 1, Vladimir Zlotopolski, Can Tran, Brit Winnen, Rikki N. Hvorup, Aaron J. Stonestrom, Elizabeth Nguyen, ⁎ Li-Wen Huang, David S. Kim, Milton H. Saier Jr. Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, USA Received 5 October 2006; received in revised form 29 December 2006; accepted 7 February 2007 Available online 17 February 2007 Abstract The genomes of eleven Gram-positive bacteria that are important for human health and the food industry, nine low G+C lactic acid bacteria and two high G+C Gram-positive organisms, were analyzed for their complement of genes encoding transport proteins. Thirteen to 18% of their genes encode transport proteins, larger percentages than observed for most other bacteria. All of these bacteria possess channel proteins, some of which probably function to relieve osmotic stress. Amino acid uptake systems predominate over sugar and peptide cation symporters, and of the sugar uptake porters, those specific for oligosaccharides and glycosides often outnumber those for free sugars. About 10% of the total transport proteins are constituents of putative multidrug efflux pumps with Major Facilitator Superfamily (MFS)-type pumps (55%) being more prevalent than ATP-binding cassette (ABC)-type pumps (33%), which, however, usually greatly outnumber all other types. An exception to this generalization is Streptococcus thermophilus with 54% of its drug efflux pumps belonging to the ABC superfamily and 23% belonging each to the Multidrug/Oligosaccharide/Polysaccharide (MOP) superfamily and the MFS.
    [Show full text]
  • The Transcriptional Regulator Lysg (Rv1985c) of Mycobacterium Tuberculosis Activates Lyse (Rv1986) in a Lysine-Dependent Manner
    RESEARCH ARTICLE The transcriptional regulator LysG (Rv1985c) of Mycobacterium tuberculosis activates lysE (Rv1986) in a lysine-dependent manner Marie Schneefeld1, Tobias Busche2, Robert Geffers3, JoÈ rn Kalinowski2*, Franz- Christoph Bange1* 1 Department of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany, 2 Microbial Genomics and Biotechnology, Center for Biotechnology, Bielefeld University, Bielefeld, Germany, 3 Research Group Genome Analytics, Helmholtz Center for Infection Research, Braunschweig, a1111111111 Germany a1111111111 a1111111111 * [email protected] (FCB); [email protected] (JK) a1111111111 a1111111111 Abstract The Mycobacterium tuberculosis protein encoded by the Rv1986 gene is a target for mem- ory T cells in patients with tuberculosis, and shows strong similarities to a lysine exporter OPEN ACCESS LysE of Corynebacterium glutamicum. During infection, the pathogen Mycobacterium tuber- Citation: Schneefeld M, Busche T, Geffers R, Kalinowski J, Bange F-C (2017) The transcriptional culosis adapts its metabolism to environmental changes. In this study, we found that the regulator LysG (Rv1985c) of Mycobacterium expression of Rv1986 is controlled by Rv1985c. Rv1985c is located directly upstream of tuberculosis activates lysE (Rv1986) in a lysine- Rv1986 with an overlapping promoter region between both genes. Semiquantitative reverse dependent manner. PLoS ONE 12(10): e0186505. transcription PCR using an isogenic mutant of Mycobacterium tuberculosis lacking Rv1985c
    [Show full text]
  • Supplemental Table 7. Every Significant Association
    Supplemental Table 7. Every significant association between an individual covariate and functional group (assigned to the KO level) as determined by CPGLM regression analysis. Variable Unit RelationshipLabel See also CBCL Aggressive Behavior K05914 + CBCL Emotionally Reactive K05914 + CBCL Externalizing Behavior K05914 + K15665 K15658 CBCL Total K05914 + K15660 K16130 KO: E1.13.12.7; photinus-luciferin 4-monooxygenase (ATP-hydrolysing) [EC:1.13.12.7] :: PFAMS: AMP-binding enzyme; CBQ Inhibitory Control K05914 - K12239 K16120 Condensation domain; Methyltransferase domain; Thioesterase domain; AMP-binding enzyme C-terminal domain LEC Family Separation/Social Services K05914 + K16129 K16416 LEC Poverty Related Events K05914 + K16124 LEC Total K05914 + LEC Turmoil K05914 + CBCL Aggressive Behavior K15665 + CBCL Anxious Depressed K15665 + CBCL Emotionally Reactive K15665 + K05914 K15658 CBCL Externalizing Behavior K15665 + K15660 K16130 KO: K15665, ppsB, fenD; fengycin family lipopeptide synthetase B :: PFAMS: Condensation domain; AMP-binding enzyme; CBCL Total K15665 + K12239 K16120 Phosphopantetheine attachment site; AMP-binding enzyme C-terminal domain; Transferase family CBQ Inhibitory Control K15665 - K16129 K16416 LEC Poverty Related Events K15665 + K16124 LEC Total K15665 + LEC Turmoil K15665 + CBCL Aggressive Behavior K11903 + CBCL Anxiety Problems K11903 + CBCL Anxious Depressed K11903 + CBCL Depressive Problems K11903 + LEC Turmoil K11903 + MODS: Type VI secretion system K01220 K01058 CBCL Anxiety Problems K11906 + CBCL Depressive
    [Show full text]
  • Supplementary Table S1. the Key Enzymes for Autotrophic Growth in C
    Electronic Supplementary Material (ESI) for Metallomics. This journal is © The Royal Society of Chemistry 2015 Supplementary Table S1. The key enzymes for autotrophic growth in C. metallidurans Name Rmet-number Spec. Predicted Mass, (kDa) Determined Mass, (kDa) Activity HOS Rmet_1522 to Rmet_1525 28.7 65.2, 25.4, 23.4, 52.8 = 166.8 62.4±1.8, 26.4±1.3, 24.0±0.6, 54.1±2.5, =235±20a HOP Rmet_1297, Rmet_1298, 67.0 69.0 + 38.6 = 108 148±24a CAX Rmet_1500, Rmet_1501 2.82 8 * (13.6 + 52.5) = 529 475±36a PRK Rmet_1512 0.994 8 * 32.4 = 259 256±11a aMean value of masses determined by S300 size exclusion chromatography and sucrose gradient centrifugation. HOS, NAD-reducing soluble hydrogenase; HOP, membrane-bound hydrogenase; CAX, ribulose-bis-phosphate carboxylase/oxygenase; PRK, phosphoribulokinase. Specific activity in U/mg protein. Supplementary Table S2. Genes expressed differently in AE104 compared to CH34 wild typea Operon Region Name Gene Q D Description UP Op1321r Rmet_4594 zntA 1.72 2.88 Q1LEH0 Heavy metal translocating P -type ATPase Op1322f Rmet_4595 czcI2 2.03 2.92 Q1LEG9 Putative uncharacterized protein Op1322f Rmet_4596 czcC2 23.34 5.36 Q1LEG8 Outer membrane efflux protein Op1322f Rmet_4597 czcB2' 15.36 9.68 Q1LEG7 Secretion protein HlyD Op0075f Rmet_0260 - 2.31 2.48 Q1LRT0 Putative transmembrane protein Op0075f Rmet_0261 coxB 2.08 2.49 Q1LRS9 Cytochrome c oxidase subunit 2 Adjacent to CMGI-7 Op0335f Rmet_1171 tnpA 7.03 21.74 Q9F8S6 Transposase (Transposase, IS4 family) CMGI-2 Op0362r Rmet_1251 tnp 4.08 0.61 Q1LNY9 Putative uncharacterized
    [Show full text]
  • Mycobacterium Tuberculosis to Eradicate Persistent Infection
    Research Collection Journal Article Derailing the aspartate pathway of Mycobacterium tuberculosis to eradicate persistent infection Author(s): Hasenoehrl, Erik J.; Sajorda, Dannah R.; Berney-Meyer, Linda; Johnson, Samantha; Tufariello, JoAnn M.; Fuhrer, Tobias; Cook, Gregory M.; Jacobs, William R., Jr.; Berney, Michael Publication Date: 2019 Permanent Link: https://doi.org/10.3929/ethz-b-000367423 Originally published in: Nature Communications 10, http://doi.org/10.1038/s41467-019-12224-3 Rights / License: Creative Commons Attribution 4.0 International This page was generated automatically upon download from the ETH Zurich Research Collection. For more information please consult the Terms of use. ETH Library ARTICLE https://doi.org/10.1038/s41467-019-12224-3 OPEN Derailing the aspartate pathway of Mycobacterium tuberculosis to eradicate persistent infection Erik J. Hasenoehrl1, Dannah Rae Sajorda1, Linda Berney-Meyer1, Samantha Johnson1, JoAnn M. Tufariello1,6, Tobias Fuhrer 2, Gregory M. Cook3,4, William R. Jacobs Jr.1,5 & Michael Berney 1 A major constraint for developing new anti-tuberculosis drugs is the limited number of validated targets that allow eradication of persistent infections. Here, we uncover a vulner- 1234567890():,; able component of Mycobacterium tuberculosis (Mtb) persistence metabolism, the aspartate pathway. Rapid death of threonine and homoserine auxotrophs points to a distinct sus- ceptibility of Mtb to inhibition of this pathway. Combinatorial metabolomic and tran- scriptomic analysis reveals that inability to produce threonine leads to deregulation of aspartate kinase, causing flux imbalance and lysine and DAP accumulation. Mtb’s adaptive response to this metabolic stress involves a relief valve-like mechanism combining lysine export and catabolism via aminoadipate.
    [Show full text]
  • Table S6. Extended Description of Enzymes, Shown in Figure S8
    Table S6. Extended description of enzymes, shown in Figure S8. Full name of enzyme Short name of enzyme ATP-binding cassette (ABC) Superfamily ABC superfamily Arsenite-Antimonite (ArsAB) Efflux family ArsAB family The F-type/V-type/A-type (F-ATPase) Superfamily F-ATPase superfamily The P-type ATPase (P-ATPase) Superfamily P-ATPase superfamily The ATP:ADP Antiporter (AAA) Family AAA family The Amino Acid/Auxin Permease (AAAP) Family AAAP family The Aspartate:Alanine Exchanger (AAE) Family AAE family The p-Aminobenzoyl-glutamate Transporter (AbgT) Family AbgT family The Arsenical Resistance-3 (ACR3) Family ACR3 family The Anion Exchanger (AE) Family AE family The Alanine or Glycine:Cation Symporter (AGCS) Family AGCS family The Amino Acid-Polyamine-Organocation (APC) Family APC family The Arsenite-Antimonite (ArsB) Efflux Family ArsB Family The Bile Acid:Na+ Symporter (BASS) Family BASS family The Betaine/Carnitine/Choline Transporter (BCCT) Family BCCT family The Benzoate:H+ Symporter (BenE) Family BenE family The Ca2+:Cation Antiporter (CaCA) Family CaCA family The Cadmium Resistance (CadD) Family CadD family The Cation-Chloride Cotransporter (CCC) Family CCC family The Cation Diffusion Facilitator (CDF) Family CDF family The Chromate Ion Transporter (CHR) Family CHR family The Citrate-Mg2+:H+Citrate-Ca2+:H+ Symporter (CitMHS) Family CitMHS family The Concentrative Nucleoside Transporter (CNT) Family CNT family The Monovalent Cation:Proton Antiporter-1 (CPA1) Family CPA1 family The Monovalent Cation:Proton Antiporter-2 (CPA2) Family CPA2
    [Show full text]
  • Mycobacterium Tuberculosis to Eradicate Persistent Infection
    ARTICLE https://doi.org/10.1038/s41467-019-12224-3 OPEN Derailing the aspartate pathway of Mycobacterium tuberculosis to eradicate persistent infection Erik J. Hasenoehrl1, Dannah Rae Sajorda1, Linda Berney-Meyer1, Samantha Johnson1, JoAnn M. Tufariello1,6, Tobias Fuhrer 2, Gregory M. Cook3,4, William R. Jacobs Jr.1,5 & Michael Berney 1 A major constraint for developing new anti-tuberculosis drugs is the limited number of validated targets that allow eradication of persistent infections. Here, we uncover a vulner- 1234567890():,; able component of Mycobacterium tuberculosis (Mtb) persistence metabolism, the aspartate pathway. Rapid death of threonine and homoserine auxotrophs points to a distinct sus- ceptibility of Mtb to inhibition of this pathway. Combinatorial metabolomic and tran- scriptomic analysis reveals that inability to produce threonine leads to deregulation of aspartate kinase, causing flux imbalance and lysine and DAP accumulation. Mtb’s adaptive response to this metabolic stress involves a relief valve-like mechanism combining lysine export and catabolism via aminoadipate. We present evidence that inhibition of the aspartate pathway at different branch-point enzymes leads to clearance of chronic infections. Together these findings demonstrate that the aspartate pathway in Mtb relies on a combination of metabolic control mechanisms, is required for persistence, and represents a target space for anti-tuberculosis drug development. 1 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA. 2 Institute of Molecular Systems Biology, Swiss Federal Institute of Technology, Zurich, Switzerland. 3 Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand. 4 Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1042, New Zealand.
    [Show full text]
  • Publications (PDF, 182
    Publications of the IBG-1 research group „Bacterial Protein Secretion“ Head: Prof. Dr. Roland Freudl ------------------------------------------------------------- 2019 ----------------------------------------------------------------- Hemmerich, J.; Moch, M.; Jurischka, S.; Wiechert, W.; Freudl, R.; Oldiges, M. (2019) Combinatorial impact of Sec signal peptides from Bacillus subtilis and bioprocess conditions on heterologous cutinase secretion by Corynebacterium glutamicum. Biotechnol. Bioeng. 116, 644-655. (https://doi.org/10.1002/bit.26873) ------------------------------------------------------------- 2018 ----------------------------------------------------------------- Ulfig, A.; Freudl, R. (2018) The early mature part of bacterial twin-arginine translocation (Tat) precursor proteins contributes to TatBC receptor binding. J Biol. Chem. 293, 7281-7299. (https://doi.org/10.1074/jbc.RA118.002576) Freudl, R. (2018) Signal peptides for recombinant protein secretion in bacterial expression systems. Microb. Cell Fact. 17:52. (https://doi.org/10.1186/s12934-018-0901-3) --------------------------------------------------------------2017 ----------------------------------------------------------------- Kleine, B.; Chattopadhyay, A.; Polen, T.; Pinto, D.; Mascher, T.; Bott, M.; Brocker, M.; Freudl, R. (2017) The three-component system EsrISR regulates a cell envelope stress response in Corynebacterium glutamicum. Mol. Microbiol. 106, 719-741. (http://dx.doi.org/10.1111/mmi.13839) Hauer, R. S.; Freudl, R.; Dittmar, J.; Jakob, M.; Klösgen, R. B.
    [Show full text]
  • Lysine Catabolism and in Vivo Substrate Specificity of D-Amino Acid Dehydrogenases in Pseudomonas Aeruginosa PAO1
    Georgia State University ScholarWorks @ Georgia State University Biology Dissertations Department of Biology 12-15-2016 Lysine Catabolism and In Vivo Substrate Specificity of D-Amino Acid Dehydrogenases in Pseudomonas Aeruginosa PAO1 Sai Madhuri Indurthi Georgia State University Follow this and additional works at: https://scholarworks.gsu.edu/biology_diss Recommended Citation Indurthi, Sai Madhuri, "Lysine Catabolism and In Vivo Substrate Specificity of D-Amino Acid Dehydrogenases in Pseudomonas Aeruginosa PAO1." Dissertation, Georgia State University, 2016. https://scholarworks.gsu.edu/biology_diss/175 This Dissertation is brought to you for free and open access by the Department of Biology at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Biology Dissertations by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. LYSINE CATABOLISM AND IN VIVO SUBSTRATE SPECIFICITY OF D-AMINO ACID DEHYDROGENASES IN PSEUDOMONAS AERUGINOSA PAO1 by SAI MADHURI INDURTHI Under the Direction of Chung-Dar Lu, PhD ABSTRACT Among multiple interconnected pathways for L-Lysine catabolism in pseudomonads, it has been reported that Pseudomonas aeruginosa PAO1 employs the decarboxylase and the transaminase pathways. However, knowledge of several genes involved in operation and regulation of these pathways was still missing. Transcriptome analyses coupled with promoter activity measurements and growth phenotype analyses led us to identify new members in L-Lys and D-Lys catabolism and regulation, including gcdR-gcdHG for glutarate utilization, dpkA, amaR-amaAB and PA2035 for D-Lys catabolism, lysR-lysXE for putative L-Lys efflux and lysP for putative L-Lys uptake. The amaAB operon is induced by L-Lys, D-Lys and pipecolate supporting the convergence of Lys catabolic pathways to pipecolate.
    [Show full text]