Molecular Microbiology

Cover image for Vol. 100 Issue 6

Early View (Online Version of Record published before inclusion in an issue)

Edited By: John D. Helmann

Impact Factor: 3.761

ISI Journal Citation Reports © Ranking: 2015: 32/123 (Microbiology); 86/289 (Biochemistry & Molecular Biology)

Online ISSN: 1365-2958

Associated Title(s): Cellular Microbiology

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  1. 1 - 56
  1. Research Articles

    1. The perilipin-like PPE15 protein in Mycobacterium tuberculosis is required for triacylglycerol accumulation under dormancy-inducing conditions

      Jaiyanth Daniel, Nidhi Kapoor, Tatiana Sirakova, Rajesh Sinha and Pappachan Kolattukudy

      Version of Record online: 21 JUN 2016 | DOI: 10.1111/mmi.13422

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      Triacylglycerol accumulation inside Mycobacterium tuberculosis is associated with its entry into a drug-tolerant, dormant state. The mycobacterial ppe15 gene is shown in this study to be essential for the accumulation of lipid droplets under dormancy-inducing conditions. Deletion of the ppe15 gene diminished the ability of the pathogen to accumulate triacylglycerol in lipid droplets and decreased its ability to develop phenotypic tolerance to rifampicin in the multiple-stress and in vitro granuloma models of dormancy.

    2. RNase E-based degradosome modulates polyadenylation of mRNAs after Rho-independent transcription terminators in Escherichia coli

      Kristen B. Mildenhall, Nicholas Wiese, Daewhan Chung, Valerie F. Maples, Bijoy K. Mohanty and Sidney R. Kushner

      Version of Record online: 16 JUN 2016 | DOI: 10.1111/mmi.13413

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      In Escherichia coli both poly(A) polymerase I (PAP I) and polynucleotide phosphorylase (PNPase) can add nucleotides to the 3′ termini of a variety of RNA molecules (mRNAs, rRNAs, tRNAs and sRNAs). However, the addition of poly(A) tails by PAP I after Rho-independent transcription terminators, surprisingly, requires both an intact RNase E-based degradosome and a functional PNPase protein.

    3. Elucidation of a mechanism of oxidative stress regulation in Francisella tularensis live vaccine strain

      Zhuo Ma, Vincenzo C. Russo, Seham M. Rabadi, Yu Jen, Sally V. Catlett, Chandra Shekhar Bakshi and Meenakshi Malik

      Version of Record online: 16 JUN 2016 | DOI: 10.1111/mmi.13426

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      Francisella tularensis is a highly virulent human pathogen. The mechanism of regulation of the oxidative stress response that facilitates the survival of F. tularensis in phagocytic cells is not known. This study characterized the role of an oxidative stress regulator, OxyR, in F. tularensis LVS. The results demonstrate that OxyR is an important virulence factor and transcriptional regulator of the oxidative stress response of F. tularensis.

  2. MicroReview

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      Interplay of regulatory RNAs and mobile genetic elements in enteric pathogens

      Kathrin S. Fröhlich and Kai Papenfort

      Version of Record online: 16 JUN 2016 | DOI: 10.1111/mmi.13428

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      Abbreviated Summary

      Small, regulatory RNAs (sRNAs) serve important roles in bacterial gene regulation. Frequently, sRNAs also function as key players in the interaction of core genome elements and horizontally-acquired DNA. This MicroReview focuses on sRNAs functioning between existing and newly obtained genetic material in enterobacterial pathogens.

  3. Research Articles

    1. Integration host factor and LuxR synergistically bind DNA to coactivate quorum-sensing genes in Vibrio harveyi

      Ryan R. Chaparian, Stephen G. Olney, Christine M. Hustmyer, Dean A. Rowe-Magnus and Julia C. van Kessel

      Version of Record online: 16 JUN 2016 | DOI: 10.1111/mmi.13425

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      The bacterial communication system called quorum sensing controls group behaviors in Vibrio harveyi through the master transcription factor LuxR. LuxR directly interacts with Integration Host Factor (IHF), a nucleoid-associated protein and global transcription regulator, and LuxR and IHF coregulate 118 genes. LuxR and IHF synergistically bind DNA to control the timing and level of expression of quorum-sensing genes, including the bioluminescence and osmotic stress response genes.

    2. You have full text access to this OnlineOpen article
      Evolved plasmid-host interactions reduce plasmid interference cost

      Hirokazu Yano, Katarznya Wegrzyn, Wesley Loftie-Eaton, Jenny Johnson, Gail E. Deckert, Linda M. Rogers, Igor Konieczny and Eva M. Top

      Version of Record online: 15 JUN 2016 | DOI: 10.1111/mmi.13407

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      The molecular mechanisms by which a broad-host-range antibiotic resistance plasmid can adapt to a novel bacterial host and increase its persistence were investigated using experimentally evolved plasmids. These evolved plasmids encode a modified replication initiation protein that simultaneously increases plasmid copy number and decreases interference cost by decreasing binding affinity to the host helicase (DnaB). This in turn causes plasmid replication to be dependent on host DnaA, an example of host specialization.

    3. L-fucose influences chemotaxis and biofilm formation in Campylobacter jejuni

      Ritika Dwivedi, Harald Nothaft, Jolene Garber, Lin Xin Kin, Martin Stahl, Annika Flint, Arnoud H. M. van Vliet, Alain Stintzi and Christine M. Szymanski

      Version of Record online: 10 JUN 2016 | DOI: 10.1111/mmi.13409

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      The influence of fucose availability on C. jejuni chemotaxis and biofilm formation was investigated. Wildtype (WT) C. jejuni forms biofilms when nutrients are limited, but swims towards L-fucose (blue ovals) and exhibits enhanced growth and reduced biofilms in its presence. Disruption of fucose uptake through mutation of the permease, fucP, results in biofilm formation even though chemotaxis is not affected. The putative dehydrogenase mutant, cj0485, abolishes both phenotypes suggesting a key role in fucose chemotaxis.

    4. A response regulator promotes Francisella tularensis intramacrophage growth by repressing an anti-virulence factor

      Kathryn M. Ramsey and Simon L. Dove

      Version of Record online: 10 JUN 2016 | DOI: 10.1111/mmi.13418

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      It was thought that the response regulator PmrA was essential for the intramacrophage growth of Francisella tularensis because it positively regulated the expression of type VI secretion genes present on the so-called Francisella Pathogenicity Island. We show instead that PmrA promotes intramacrophage growth by repressing a gene that encodes a previously unknown anti-virulence factor. This PmrA-repressed gene is the first F. tularensis gene we are aware of that can interfere with intramacrophage growth and survival.

  4. MicroReviews

    1. The magic dance of the alarmones (p)ppGpp

      Wieland Steinchen and Gert Bange

      Version of Record online: 10 JUN 2016 | DOI: 10.1111/mmi.13412

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      The alarmones (p)ppGpp are essential second messengers conserved among bacteria and the plant chloroplasts. This review discusses the molecular plasticity of enzymes and targets involved in (p)ppGpp metabolism and regulation, respectively.

  5. Research Articles

    1. Function, expression, specificity, diversity and incompatibility of actinobacteriophage parABS systems

      Rebekah M. Dedrick, Travis N. Mavrich, Wei L. Ng, Juan C. Cervantes Reyes, Matthew R. Olm, Rachael E. Rush, Deborah Jacobs-Sera, Daniel A. Russell and Graham F. Hatfull

      Version of Record online: 10 JUN 2016 | DOI: 10.1111/mmi.13414

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      Over 40 completely sequenced temperate actinobacteriophages encode diverse Type Ib partitioning cassettes containing parA and parB genes as well as centromere-like sites parS-L and parS-R. Their prophages replicate extrachromosomally at low copy number and the partitioning systems mediate prophage maintenance, although related phages exhibit lysogenic incompatibility through competition of ParB binding to the parS sites.

    2. A spectrum of CodY activities drives metabolic reorganization and virulence gene expression in Staphylococcus aureus

      Nicholas R. Waters, David J. Samuels, Ranjan K. Behera, Jonathan Livny, Kyu Y. Rhee, Marat R. Sadykov and Shaun R. Brinsmade

      Version of Record online: 10 JUN 2016 | DOI: 10.1111/mmi.13404

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      By analyzing transcriptome profiles and assessing in vitro phenotypes of S. aureus strains producing variants of CodY with variable activity, we shed light on an important link between metabolism and virulence. We show that nutrient acquisition and synthesis, as well as biofilm formation and nuclease production are under graded CodY control. We infer that CodY plays a crucial role in orchestrating responses to environmental nutrient stress, including responses that can be detrimental to the host.

    3. Molybdate uptake by Agrobacterium tumefaciens correlates with the cellular molybdenum cofactor status

      Marie-Christine Hoffmann, Koral Ali, Marleen Sonnenschein, Laura Robrahn, Daria Strauss, Franz Narberhaus and Bernd Masepohl

      Version of Record online: 10 JUN 2016 | DOI: 10.1111/mmi.13421

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      Most bacteria synthesize high-affinity molybdate (Mo) transporters, ModABC, under Mo-limiting conditions. Under Mo-replete conditions, modABC transcription is repressed by molybdate-binding ModE regulators in Escherichia coli and other bacteria. Here, we characterized a ModE regulator lacking a molybdate-binding domain (ModES) from Agrobacterium tumefaciens. We provide first evidence that modABC repression requires the molybdenum cofactor, Moco, rather than directly responding to molybdate in A. tumefaciens and possibly also in other species lacking a full-length ModE regulator.

    4. The function of the PduJ microcompartment shell protein is determined by the genomic position of its encoding gene

      Chiranjit Chowdhury, Sunny Chun, Michael R. Sawaya, Todd O. Yeates and Thomas A Bobik

      Version of Record online: 7 JUN 2016 | DOI: 10.1111/mmi.13423

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      Abbreviated Summary

      Deletion of the pduA gene impairs the function of the 1,2-propanediol utilization microcompartment of Salmonella (Pdu MCP). When PduJ (a close homologue of PduA) is expressed from plasmid, it does not correct the defects of a ΔpduA mutant. However, when PduJ is expressed from the pduA chromosomal locus, it restores normal MCP function. Thus, we propose that the function of the pduJ gene is dependent on the genomic position of its encoding gene.

    5. Glucose induces delocalization of a flagellar biosynthesis protein from the flagellated pole

      Soyoung Park, Young-Ha Park, Chang-Ro Lee, Yeon-Ran Kim and Yeong-Jae Seok

      Version of Record online: 3 JUN 2016 | DOI: 10.1111/mmi.13424

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      Abbreviated Summary

      Making a right decision to stay or move is critical for survival in a changing environment. Here we identify a novel mechanism for glucose-dependent on-off switching of flagellar synthesis in Vibrio vulnificus: When enzyme IIAGlc of the bacterial PEP:carbohydrate phosphotransferase system is dephosphorylated in the presence glucose, it delocalizes a protein required for flagellar biosynthesis from the flagellated pole. This leads to a loss of motility and enables bacteria to stay in a favorable habitat.

    6. The Saccharomyces cerevisiae Ptc1 protein phosphatase attenuates G2-M cell cycle blockage caused by activation of the cell wall integrity pathway

      Laura Tatjer, Asier González, Albert Serra-Cardona, Anna Barceló, Antonio Casamayor and Joaquín Ariño

      Version of Record online: 3 JUN 2016 | DOI: 10.1111/mmi.13416

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      Activation of the cell wall integrity pathway leads to phosphorylation of Cdc28 and delay in cell cycle progression at the G2-M transition. By dephosphorylating and inhibiting the MAPK kinase Mkk1, the Ptc1 phosphatase avoids excessive activation of the Sl2 MAPK and contributes to resume cell cycle.

    7. Rearrangements of α-helical structures of FlgN chaperone control the binding affinity for its cognate substrates during flagellar type III export

      Miki Kinoshita, Yuki Nakanishi, Yukio Furukawa, Keiichi Namba, Katsumi Imada and Tohru Minamino

      Version of Record online: 3 JUN 2016 | DOI: 10.1111/mmi.13415

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      The structure and structure-based functional analyses reveal that the N-loop between α1 and α2 of FlgN acts as a structural switch for the rearrangement of three α helices to control the binding affinity of helix α3 for FlgK.

    8. Structural insights into the inhibition mechanism of bacterial toxin LsoA by bacteriophage antitoxin Dmd

      Hua Wan, Yuichi Otsuka, Zeng-Qiang Gao, Yong Wei, Zhen Chen, Michiaki Masuda, Tetsuro Yonesaki, Heng Zhang and Yu-Hui Dong

      Version of Record online: 2 JUN 2016 | DOI: 10.1111/mmi.13420

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      The antitoxin Dmd from T4 phage is inserted into the deep groove between the N-terminal repeated domain (NRD) and the Dmd-binding domain (DBD) of Escherichia coli toxin LsoA. The conserved Dmd-interacting residues in this groove are vital for LsoA toxicity generated by its RNase activity. Therefore, Dmd can recognize LsoA and inhibit its toxicity by occupying the active site via substrate RNA mimicry.

    9. Concerted action of NIC relaxase and auxiliary protein MobC in RA3 plasmid conjugation

      Jolanta Godziszewska, Gabriel Moncalián, Matilde Cabezas, Aneta A. Bartosik, Fernando de la Cruz and Grazyna Jagura-Burdzy

      Version of Record online: 2 JUN 2016 | DOI: 10.1111/mmi.13401

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      The mobC-nic operon of broad-host-range conjugative RA3 plasmid (IncU incompatibility group) encodes HUH relaxase NIC (MOBP4 subgroup) and a transcriptional regulator MobC. Here we delineated minimal oriTRA3, identified the NIC_RA3 binding site and its metal ions preference. The interplay between these two proteins was demonstrated: the MobC participates in the efficient NIC cleavage of supercoiled oriTRA3 and NIC_RA3 potentiates the MobC repression of the mobC promoter.

    10. Cyclic diguanylate regulation of Bacillus cereus group biofilm formation

      Annette Fagerlund, Veronika Smith, Åsmund K. Røhr, Toril Lindbäck, Marthe P. Parmer, K. Kristoffer Andersson, Leon Reubsaet and Ole Andreas Økstad

      Version of Record online: 2 JUN 2016 | DOI: 10.1111/mmi.13405

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      By a genome-wide approach, we show that the second messenger cyclic-di-GMP regulates biofilm formation, and also affects motility and cytotoxicity, in Bacillus thuringiensis 407. Furthermore, genes linked to c-di-GMP responses (cdg genes) were found to be ubiquitous in Bacillus cereus group bacteria, including the obligate human pathogen Bacillus anthracis. Only two of the cdg genes had orthologs in Bacillus subtilis, highlighting differences in c-di-GMP signalling between B. subtilis and B. cereus group bacteria.

    11. A protein complex supports the production of Spo0A-P and plays additional roles for biofilms and the K-state in Bacillus subtilis

      Eugenie J. Dubnau, Valerie J. Carabetta, Andrew W. Tanner, Mathieu Miras, Christine Diethmaier and David Dubnau

      Version of Record online: 2 JUN 2016 | DOI: 10.1111/mmi.13411

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      In Bacillus subtilis, the proteins YlbF, YmcA and YaaT form a complex needed for the formation of biofilms, for sporulation and for genetic transformation. This paper strongly supports a role for these proteins in stimulating the phosphorylation of the key transcription factor, Spo0A. The present data contradict an alternative published model that proposed a role for the complex in destabilizing the mRNA for SinR, a repressor of biofilm formation.

    12. A new piperidinol derivative targeting mycolic acid transport in Mycobacterium abscessus

      Christian Dupont, Albertus Viljoen, Faustine Dubar, Mickaël Blaise, Audrey Bernut, Alexandre Pawlik, Christiane Bouchier, Roland Brosch, Yann Guérardel, Joël Lelièvre, Lluis Ballell, Jean-Louis Herrmann, Christophe Biot and Laurent Kremer

      Version of Record online: 1 JUN 2016 | DOI: 10.1111/mmi.13406

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      The piperidinol-based lead compound PIPD1 inhibits growth of Mycobacterium abscessus by targeting MAB_4508, an MmpL family member participating in the transport of trehalose monomycolate (TMM), leading to the loss of arabinogalactan mycolylation. Multiple mutations in MAB_4508 conferring high resistance levels to PIPD1 helped to define a potential PIPD1-binding pocket. Our findings emphasize a yet unexploited chemical structure class against M. abscessus infections with promising translational development possibilities.

  6. MicroCommentary

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  7. Research Articles

    1. You have full text access to this OnlineOpen article
      Base J represses genes at the end of polycistronic gene clusters in Leishmania major by promoting RNAP II termination

      David L. Reynolds, Brigitte T. Hofmeister, Laura Cliffe, T. Nicolai Siegel, Britta A. Anderson, Stephen M. Beverley, Robert J. Schmitz and Robert Sabatini

      Version of Record online: 1 JUN 2016 | DOI: 10.1111/mmi.13408

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      Base J regulates gene expression by stimulating premature termination within gene clusters in Leishmania major. Loss of base J within gene clusters leads to read through transcription and upregulation of genes downstream of base J. The loss of base J at the end of gene clusters results in read through transcription into the opposing gene clusters. However, transcription of the opposing DNA strand has no effect on mRNA levels from the sense strand.

    2. PbsP, a cell wall-anchored protein that binds plasminogen to promote hematogenous dissemination of group B Streptococcus

      Marco Buscetta, Arnaud Firon, Giampiero Pietrocola, Carmelo Biondo, Giuseppe Mancuso, Angelina Midiri, Letizia Romeo, Roberta Galbo, Mario Venza, Isabella Venza, Pierre-Alexandre Kaminski, Myriam Gominet, Giuseppe Teti, Pietro Speziale, Patrick Trieu-Cuot and Concetta Beninati

      Version of Record online: 1 JUN 2016 | DOI: 10.1111/mmi.13357

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      We describe here Plasminogen binding surface Protein, or PbsP, a highly conserved virulence factor of group B streptococci. This adhesin contains two Streptococcal Surface Repeat domains, a methionine- and lysine-rich region and an LPXTG cell-wall anchoring motif. PbsP largely mediates the ability of group B streptococcal strain NEM316 to bind plasminogen, acquire proteolytic activity and transmigrate through brain endothelial cells, resulting in meningoencephalitis. Moreover, immunization of mice with PbsP confers protective immunity.

    3. A scaffold protein connects type IV pili with the Chp chemosensory system to mediate activation of virulence signaling in Pseudomonas aeruginosa

      Yuki F. Inclan, Alexandre Persat, Alexander Greninger, John Von Dollen, Jeffery Johnson, Nevan Krogan, Zemer Gitai and Joanne N. Engel

      Version of Record online: 27 MAY 2016 | DOI: 10.1111/mmi.13410

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      Type IV pili (TFP) function as mechanosensors to trigger acute virulence programs in Pseudomonas aeruginosa by signaling through the Chp chemosensory system. We show that FimL, a Chp chemosensory system accessory protein of unknown function, acts as a scaffold to enable spatial colocalization of TFP and Chp system components to coordinate cAMP-dependent transcription of virulence genes upon surface contact. These components are found in other TFP-expressing bacteria, suggesting that mechanochemical surface sensing may be widespread.

    4. A structural comparison of Listeria monocytogenes protein chaperones PrsA1 and PrsA2 reveals molecular features required for virulence

      Laty A. Cahoon, Nancy E. Freitag and Gerd Prehna

      Version of Record online: 27 MAY 2016 | DOI: 10.1111/mmi.13367

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      Listeria monocytogenes PrsA2 is a secreted chaperone that contributes to the folding of proteins translocated across the bacterial membrane and is required for virulence. Targeted mutagenesis based on structure demonstrates that oligomerization of PrsA2 as well as molecular features of the foldase domain are required for protein secretion and virulence, and a functional role was uncovered for the related PrsA1 protein in bacterial resistance to alcohol.

    5. A novel flagellar sheath protein, FcpA, determines filament coiling, translational motility and virulence for the Leptospira spirochete

      Elsio A. Wunder Jr., Cláudio P. Figueira, Nadia Benaroudj, Bo Hu, Brian A. Tong, Felipe Trajtenberg, Jun Liu, Mitermayer G. Reis, Nyles W. Charon, Alejandro Buschiazzo, Mathieu Picardeau and Albert I. Ko

      Version of Record online: 24 MAY 2016 | DOI: 10.1111/mmi.13403

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      Spirochete is a unique group of bacteria with a distinguish morphology and the presence of periplasmic flagella. Both features are essential for their ability to produce thrust even when in contact with high viscous media. In the present report, we describe a novel protein, FcpA, which is expressed exclusively in Leptospira species, confers the unique structural feature of coiled purified flagella, and is essential for the hooked-end morphology of the bacteria. FcpA is an abundant surface expressed protein in the flagella structure, and is fundamental for the pathogen's ability to produce translational motility and virulence.

    6. Coordinated disassembly of the divisome complex in Escherichia coli

      Bill Söderström, Kiavash Mirzadeh, Stephen Toddo, Gunnar von Heijne, Ulf Skoglund and Daniel O. Daley

      Version of Record online: 23 MAY 2016 | DOI: 10.1111/mmi.13400

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      The divisome is the macromolecular complex that carries out cell division in E. coli. Every generation it must be assembled, and then disassembled so that the sequestered proteins can be recycled. Our study shows disassembly occurs in a co-ordinated process that consists of at least five steps. The process is remarkably similar to assembly, indicating that disassembly follows a first-in, first-out principle. We also show that the divisome structure is composed of two concentric rings.

    7. Identification of a cis-acting element in nitrogen fixation genes recognized by CnfR in the nonheterocystous nitrogen-fixing cyanobacterium Leptolyngbya boryana

      Ryoma Tsujimoto, Narumi Kamiya and Yuichi Fujita

      Version of Record online: 23 MAY 2016 | DOI: 10.1111/mmi.13402

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      CnfR is the master transcriptional activator for nitrogen fixation (nif) genes in the cyanobacterium Leptolyngbya boryana. The nif gene cluster in L. boryana is divided into right and left parts by the intergenic region of nifB and nifP, and these nif genes are divergently transcribed from this region. We found a cis-acting element recognized by CnfR by a reporter system in the non-nitrogen fixing cyanobacterium Synechocystis sp. PCC 6803. In the cis-element, six motifs are essential for the transcriptional activation by CnfR. CnfR induced by NtcA may be converted to an active form in low-oxygen and nitrogen-deficient conditions to activate the transcription of the nif genes.

    8. Vital and dispensable roles of Plasmodium multidrug resistance transporters during blood- and mosquito-stage development

      Sanna R. Rijpma, Maarten van der Velden, Takeshi Annoura, Joachim M. Matz, Sanketha Kenthirapalan, Taco W. A. Kooij, Kai Matuschewski, Geert-Jan van Gemert, Marga van de Vegte-Bolmer, Rianne Siebelink-Stoter, Wouter Graumans, Jai Ramesar, Onny Klop, Frans G. M. Russel, Robert W. Sauerwein, Chris J. Janse, Blandine M. Franke-Fayard and Jan B. Koenderink

      Version of Record online: 23 MAY 2016 | DOI: 10.1111/mmi.13373

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      The role of MDR transporters of the ABC superfamily was evaluated in Plasmodium by targeting seven transporter genes, of which three could be successfully deleted. Loss of P. falciparum MDR2 results in reduced asexual growth, while in P. berghei this was the case for MDR3 and MDR5. Interestingly, deletion of MDR2 and MDR5 causes a reduction in oocyst and sporozoite production in both species, indicating a role for ABC transporters in transmission stages.

  8. MicroReviews

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      Ticket to ride: export of proteins to the Plasmodium falciparum-infected erythrocyte

      Jude M. Przyborski, Britta Nyboer and Michael Lanzer

      Version of Record online: 23 MAY 2016 | DOI: 10.1111/mmi.13380

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      Here, we review recent advances in our understanding of protein export in malaria parasites, and highlight gaps in our knowledge that may form the basis for future research.

  9. Research Articles

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      Complex polar machinery required for proper chromosome segregation in vegetative and sporulating cells of Bacillus subtilis

      Tomas G. Kloosterman, Rok Lenarcic, Clare R. Willis, David M. Roberts, Leendert W. Hamoen, Jeff Errington and Ling J. Wu

      Version of Record online: 18 MAY 2016 | DOI: 10.1111/mmi.13393

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      During spore development in Bacillus subtilis, the MinD and ComN proteins take on new roles that are unrelated to their functions in vegetative growth, forming a polar complex which recruits the origin of replication (oriC) region of the chromosome to the cell pole in a pathway that is separate from the sporulation-specific RacA pathway of oriC placement.

    2. SilE is an intrinsically disordered periplasmic “molecular sponge” involved in bacterial silver resistance

      Karishma R. Asiani, Huw Williams, Louise Bird, Matthew Jenner, Mark S. Searle, Jon L. Hobman., David J. Scott and Panos Soultanas

      Version of Record online: 7 MAY 2016 | DOI: 10.1111/mmi.13399

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      We show that the periplasmic SilE protein, which is part of the silver resistance machinery of Escherichia coli, is an intrinsically disordered protein in its apo-form and folds to a holo-form upon binding to Ag+ ions. Maximal folding is induced upon binding to six Ag+ ions but each holo-SilE molecule can bind up to eight Ag+ ions. Coordination of Ag+ ions is mediated via conserved histidine and methionine residues arranged in two characteristic motifs (MxxHxxxxxxHxxMxx and HxxMxxxHxxMxx). SilE may act as a metal-ion chaperone to transport Ag+ ions to the SilABC transporter and/or signal via the histidine kinase sensor SilS to activate the remainder of the silver resistance machinery.

  10. MicroReviews

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      Novel mechanisms power bacterial gliding motility

      Beiyan Nan and David R. Zusman

      Version of Record online: 7 MAY 2016 | DOI: 10.1111/mmi.13389

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      Surfaces are natural habitats for many bacterial species. Some bacteria glide on surfaces without the aid of traditional flagella or pili. The mechanisms of gliding are not well understood. Recent advances revealed that gliding in different bacteria involves diverse motors and a broad spectrum of mechanisms. This review summarizes recent findings on the gliding mechanisms of the myxobacteria, flavobacteria and mycoplasmas.

  11. Research Articles

    1. CRISPR-Cas9-modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine-containing compounds but potentiates artemisinin-based combination therapy partner drugs

      Caroline L. Ng, Giulia Siciliano, Marcus C. S. Lee, Mariana J. de Almeida, Victoria C. Corey, Selina E. Bopp, Lucia Bertuccini, Sergio Wittlin, Rachel G. Kasdin, Amélie Le Bihan, Martine Clozel, Elizabeth A. Winzeler, Pietro Alano and David A. Fidock

      Version of Record online: 7 MAY 2016 | DOI: 10.1111/mmi.13397

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      Thse piperazine-containing compound ACT-451840 is a potent inhibitor of Plasmodium falciparum asexual blood stages and gametocytes. Using selection studies and CRISPR-Cas9 gene editing, we show that resistance can be mediated via mutations in the ATP-binding cassette transporter PfMDR1. These mutations can also sensitize these malaria parasites to the first-line drugs lumefantrine and mefloquine. Exploiting PfMDR1 resistance provides opportunities to develop novel disease-relieving and transmission-blocking antimalarials.

    2. NapM, a new nucleoid-associated protein, broadly regulates gene expression and affects mycobacterial resistance to anti-tuberculosis drugs

      Yu Liu, Hongyang Wang, Tao Cui, Xiling Zhou, Yanxia Jia, Hua Zhang and Zheng-Guo He

      Version of Record online: 7 MAY 2016 | DOI: 10.1111/mmi.13383

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      NapM represents a new nucleoid-associated protein and is conserved in all of the sequenced mycobacterial genomes. It recognizes DNA in a length-dependent but sequence-independent manner. NapM globally regulates the expression of more than 150 genes and the resistance of Mycobacterium smegmatis to two anti-tuberculosis drugs.

    3. L-2,3-diaminopropionate generates diverse metabolic stresses in Salmonella enterica

      Dustin C. Ernst, Mary E. Anderson and Diana M. Downs

      Version of Record online: 6 MAY 2016 | DOI: 10.1111/mmi.13384

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      L-2,3-diaminopropionic acid (Dap) is an important molecular building block found throughout nature. Our report describes the specific metabolic consequences of Dap accumulation in S. enterica, and demonstrates the importance of RidA in preventing 2-aminoacrylate stress encountered as a by-product of Dap degradation.

    4. Plasmenylethanolamine synthesis in Leishmania major

      Mattie C. Pawlowic, Fong-fu Hsu, Samrat Moitra, Neha Biyani and Kai Zhang

      Version of Record online: 6 MAY 2016 | DOI: 10.1111/mmi.13387

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      Leishmania parasites synthesize a high level of plasmenylethanolamine (PME), a special class of glycerophospholipids. Effects of PME synthesis on Leishmania survival and virulence are investigated in this study.

    5. Discovery of a novel periplasmic protein that forms a complex with a trimeric autotransporter adhesin and peptidoglycan

      Masahito Ishikawa, Shogo Yoshimoto, Ayumi Hayashi, Junichi Kanie and Katsutoshi Hori

      Version of Record online: 6 MAY 2016 | DOI: 10.1111/mmi.13398

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      Trimeric autotransporter adhesins (TAAs) usually form homotrimer on bacterial cell surfaces. AtaA is a TAA of Acinetobacter sp. Tol 5. We identified tpgA, which is transcribed with ataA, encodes a periplasmic protein forming a complex with AtaA and peptidoglycan, and functions to assist an efficient surface display of AtaA. The genes encoding the TAA–TpgA-like protein cassette can be found in diverse Gram-negative bacteria, suggesting a common contribution of TpgA homologues to TAA biogenesis.

    6. Identification and functional characterization of lysine methyltransferases of Entamoeba histolytica

      Jessica Borbolla-Vázquez, Esther Orozco, Christian Medina-Gómez, Aarón Martínez-Higuera, Rosario Javier-Reyna, Bibiana Chávez, Abigail Betanzos and Mario A. Rodríguez

      Version of Record online: 6 MAY 2016 | DOI: 10.1111/mmi.13394

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      We identified four HKMTs in E. histolytica (EhHKMT1 to EhHKMT4). Enzymatic assays indicated that all of them are able to transfer methyl groups to commercial histones. EhHKMT1, EhHKMT2 and EhHKMT4 were detected in nucleus and cytoplasm of trophozoites. EhHKMT2 and EhHKMT4 were located in phagosomes associated with EhADH, a protein involved in the phagocytosis of this parasite. Results suggest that E. histolytica uses its HKMTs to regulate transcription by epigenetic mechanisms, and at least two of them could also be implicated in methylation of proteins that participate in phagocytosis.

    7. You have full text access to this OnlineOpen article
      A large family of anti-activators accompanying XylS/AraC family regulatory proteins

      Araceli E. Santiago, Michael B. Yan, Minh Tran, Nathan Wright, Deborah H. Luzader, Melissa M. Kendall, Fernando Ruiz-Perez and James P. Nataro

      Version of Record online: 6 MAY 2016 | DOI: 10.1111/mmi.13392

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      AraC Negative Regulators (ANR) suppress virulence genes by directly down-regulating AraC/XylS members in Gram-negative bacteria. In this study we provide important insights into mechanistic aspects of the ANR family. By employing a bacterial two hybrid system, pull-down assays, and surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR-activated regulator), a prototype member of ANR family in EAEC, binds with high affinity to the N-terminal linker domain of AraC-like member AggR. Binding of Aar to AggR disrupted the ability of the latter to bind DNA. Our finding suggested that ANR is a common, highly conserved mechanism of regulation of the AraC family.

    8. You have full text access to this OnlineOpen article
      The green tea polyphenol EGCG inhibits E. coli biofilm formation by impairing amyloid curli fibre assembly and downregulating the biofilm regulator CsgD via the σE-dependent sRNA RybB

      Diego O. Serra, Franziska Mika, Anja M. Richter and Regine Hengge

      Version of Record online: 6 MAY 2016 | DOI: 10.1111/mmi.13379

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      Bacterial biofilms are characterized by an extracellular matrix containing amyloid fibres, exopolysaccharide and other biopolymers which contributes to the pronounced antibiotic resistance of biofilms. Using Escherichia coli macrocolonies as a model biofilm, the green tea polyphenol epigallocatachin gallate is shown here to be a potent antibiofilm agent. Its mechanisms of action affect molecular processes of general importance for bacterial biofilm matrix formation, suggesting applications as an adjuvant in antibiotic and biofilm-related intestinal infection therapy.

    9. A novel membrane anchor for FtsZ is linked to cell wall hydrolysis in Caulobacter crescentus

      Elizabeth L. Meier, Shiva Razavi, Takanari Inoue and Erin D. Goley

      Version of Record online: 3 MAY 2016 | DOI: 10.1111/mmi.13388

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      The bacterial tubulin homolog FtsZ forms a ring (Z-ring) at midcell essential for division. Membrane attachment has long been considered central to FtsZ function, yet few membrane anchors have been studied. We characterized a novel FtsZ membrane anchor in Caulobacter crescentus, FzlC. In vitro FzlC binds and recruits FtsZ to membranes while in vivo synthetic interactions implicate FzlC in cell wall hydrolysis. FzlC thus represents a new link between the Z-ring and cell wall remodeling.

    10. Polyphosphate is involved in cell cycle progression and genomic stability in Saccharomyces cerevisiae

      Samuel Bru, Joan Marc Martínez-Laínez, Sara Hernández-Ortega, Eva Quandt, Javier Torres-Torronteras, Ramón Martí, David Canadell, Joaquin Ariño, Sushma Sharma, Javier Jiménez and Josep Clotet

      Version of Record online: 3 MAY 2016 | DOI: 10.1111/mmi.13396

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      The phosphate concentration in cells remains constant through the cell cycle, although there are stages where a higher demand of phosphate is required (DNA replication). The faithful duplication of genomes is reliant upon a constant supply of deoxynucleotide triphosphates (dNTP). Here, we show that the degradation of polyphosphate is involved in buffering the cyclical intracellular variations in the phosphate concentration and thus is an important process in sustaining dNTP synthesis and maintaining correct cell proliferation.

    11. The hypoxia-induced dehydrogenase HorA is required for coenzyme Q10 biosynthesis, azole sensitivity and virulence of Aspergillus fumigatus

      Kristin Kroll, Elena Shekhova, Derek J. Mattern, Andreas Thywissen, Ilse D. Jacobsen, Maria Strassburger, Thorsten Heinekamp, Ekaterina Shelest, Axel A. Brakhage and Olaf Kniemeyer

      Version of Record online: 3 MAY 2016 | DOI: 10.1111/mmi.13377

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      Here we characterized the fungus-specific mitochondrial oxidoreductase HorA in Aspergillus fumigatus. HorA is involved in the coenzyme Q biosynthesis and consequently important for function of respiratory chain complex I and redox homeostasis. Our results indicate that HorA is crucial for virulence and drug tolerance of A. fumigatus. Moreover, HorA conceptionally provides an attractive mitochondrial target for therapy of fungal infections due to its absence in mammals.

    12. A role for adenine nucleotides in the sensing mechanism to purine starvation in Leishmania donovani

      Jessica L. Martin, Phillip A. Yates, Jan M. Boitz, Dennis R. Koop, Audrey L. Fulwiler, Maria Belen Cassera, Buddy Ullman and Nicola S. Carter

      Version of Record online: 3 MAY 2016 | DOI: 10.1111/mmi.13390

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      Purine-sensing in Leishmania donovani: perturbation of intracellular adenine nucleotide levels trigger an adaptive response to extracellular purine restriction and ensure prolonged parasite survival within a purine scarce environment.

    13. Direct sensing and signal transduction during bacterial chemotaxis toward aromatic compounds in Comamonas testosteroni

      Zhou Huang, Bin Ni, Cheng-Ying Jiang, Yu-Fan Wu, Yun-Zhe He, Rebecca E. Parales and Shuang-Jiang Liu

      Version of Record online: 2 MAY 2016 | DOI: 10.1111/mmi.13385

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      • The existence of chemoreceptors that bind to aromatic attractants and subsequently trigger chemotaxis had long been speculated, but not demonstrated.
      • Though a series of phenotype screening and biochemical identification, a new methyl-accepting chemotaxis protein (MCP) namely MCP2901 in Comamonas testosteroni was evidenced to mediate chemotaxis to 2,6-dihydroxybenzoate and 2-hydroxybenzoate by direct binding. Results demonstrated also that MCP2901 triggered chemotaxis via binding to citrate.
    14. The cytochrome bd oxidase of Escherichia coli prevents respiratory inhibition by endogenous and exogenous hydrogen sulfide

      Sergey Korshunov, Karin R. C. Imlay and James A. Imlay

      Version of Record online: 2 MAY 2016 | DOI: 10.1111/mmi.13372

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      Toxic levels of intracellular sulfide arise either from the degradation of excess cysteine or from an influx of hydrogen sulfide itself. Sulfide inhibits the primary respiratory cytochrome bo oxidase, and continued respiration depends upon the presence of the secondary cytochrome bd oxidase. This scenario is likely common to sulfidic environments, such as the mammalian gut.

    15. BcIqg1, a fungal IQGAP homolog, interacts with NADPH oxidase, MAP kinase and calcium signaling proteins and regulates virulence and development in Botrytis cinerea

      Robert Marschall and Paul Tudzynski

      Version of Record online: 29 APR 2016 | DOI: 10.1111/mmi.13391

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      A homolog of the RasGAP scaffold protein IQGAP links cytosolic and catalytic NADPHoxidase subunits in the grey mold fungus Botrytis cinerea, interacts with modules of the MAP kinase- and calcium-dependent signaling pathways, and is involved in resistance against oxidative and membrane stress and in several developmental processes such as formation of sclerotia, conidial anastomosis tubes and infection cushions as well as in virulence.

    16. CDK phosphorylates the polarisome scaffold Spa2 to maintain its localization at the site of cell growth

      Haitao Wang, Zhen-Xing Huang, Jie Ying Au Yong, Hao Zou, Guisheng Zeng, Jiaxin Gao, Yanming Wang, Ada Hang-Heng Wong and Yue Wang

      Version of Record online: 20 APR 2016 | DOI: 10.1111/mmi.13386

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      Polarisome is a protein complex that plays an important role in polarized growth in fungi. Polarisome must localize to the right place at the right time for normal morphogenesis. We demonstrate that the cyclin dependent kinase Cdc28 in association with cyclins Clb2 and Hgc1 phosphorylates the polarisome scaffold Spa2 and maintains polarisome localization at the bud tip during yeast growth and at the hyphal tip during hyphal growth in the dimorphic fungus Candida albicans.

    17. Production of the Streptomyces scabies coronafacoyl phytotoxins involves a novel biosynthetic pathway with an F420-dependent oxidoreductase and a short-chain dehydrogenase/reductase

      Luke Bown, Mead S. Altowairish, Joanna K. Fyans and Dawn R. D. Bignell

      Version of Record online: 20 APR 2016 | DOI: 10.1111/mmi.13378

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      Coronafacoyl phytotoxins are plant hormone mimics that are produced by multiple phytopathogenic bacteria, including Pseudomonas syringae and Streptomyces scabies. In this study, we show that the biosynthesis of coronafacoyl-isoleucine in S. scabies involves two genes, oxr and sdr, which encode a predicted oxidoreductase and a short-chain dehydrogenase/reductase respectively. Such enzymes have not been implicated in coronafacoyl phytotoxin production previously, and our results suggest that S. scabies utilizes a novel biosynthetic pathway for phytotoxin production.

    18. Tpd3-Pph21 phosphatase plays a direct role in Sep7 dephosphorylation in Candida albicans

      Qizheng Liu, Qi Han, Na Wang, Guangyin Yao, Guisheng Zeng, Yanming Wang, Zhenxing Huang, Jianli Sang and Yue Wang

      Version of Record online: 20 APR 2016 | DOI: 10.1111/mmi.13376

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      Septins are a component of the cytoskeleton and play important roles in cell cycle control, cytokinesis, and polarized growth. In fungi, septin organization and function are regulated by phosphorylation. Here, we demonstrate the PP2A family Tpd3-Pph21 phosphatase dephophorylates the septin Sep7 in the fungal pathogen Candida albicans, which is important for morphogenesis, cytokinesis, and virulence.

    19. Metal-specific control of gene expression mediated by Bradyrhizobium japonicum Mur and Escherichia coli Fur is determined by the cellular context

      Thomas H. Hohle and Mark R. O'Brian

      Version of Record online: 17 APR 2016 | DOI: 10.1111/mmi.13381

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      The iron-dependent transcriptional regulator Fur from E. coli (ecFur) responds to manganese when expressed in Bradyrhizobium japonicum. Similarly, the manganese-dependent regulator Mur from B. japonicum represses genes in an iron-dependent manner in E. coli. Thus, the cellular environment is a major factor in determining metal selectivity of the two Fur family proteins. The findings likely explain why B. japonicum and related bacteria do not harbor Fur to mediate iron control of gene expression

    20. You have full text access to this OnlineOpen article
      Acyldepsipeptide antibiotics kill mycobacteria by preventing the physiological functions of the ClpP1P2 protease

      Kirsten Famulla, Peter Sass, Imran Malik, Tatos Akopian, Olga Kandror, Marina Alber, Berthold Hinzen, Helga Ruebsamen-Schaeff, Rainer Kalscheuer, Alfred L. Goldberg and Heike Brötz-Oesterhelt

      Version of Record online: 1 APR 2016 | DOI: 10.1111/mmi.13362

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      The mechanism of action of antibiotic acyldepsipeptides (ADEP) has been commonly accepted to function by activating unregulated protease activity of bacterial ClpP peptidase. Here, we show enhanced killing by ADEP upon depletion of the ClpP1P2 level in a conditional Mycobacterium bovis BCG mutant. Our data reveal killing of mycobacteria by ADEPs through abrogating the interaction between ClpP and its cognate Clp-ATPases rather than ClpP activation like in many other bacteria.

    21. Listeria monocytogenes wall teichoic acid decoration in virulence and cell-to-cell spread

      Patricia A. Spears, Edward A. Havell, Terri S. Hamrick, John B. Goforth, Alexandra L. Levine, S. Thomas Abraham, Christian Heiss, Parastoo Azadi and Paul E. Orndorff

      Version of Record online: 10 MAR 2016 | DOI: 10.1111/mmi.13353

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      Phage resistant (ΦR) Listeria monocytogenes mutants (green) exhibit short actin tails (red) during cytosolic growth, and spread cell-to-cell poorly compared to the parent. Phage resistance was associated with the absence of a single decorating sugar (galactose) on wall teichoic acid (WTA). The mutants were additionally dramatically attenuated in a mouse oral infection model. A hypothetical pathway for WTA galactosylation is proposed.

    22. Highly conserved nucleotide phosphatase essential for membrane lipid homeostasis in Streptococcus pneumoniae

      Kirsten Kuipers, Clement Gallay, Václav Martínek, Manfred Rohde, Markéta Martínková, Samantha L. van der Beek, Wouter S. P. Jong, Hanka Venselaar, Aldert Zomer, Hester Bootsma, Jan-Willem Veening and Marien I. de Jonge

      Version of Record online: 19 FEB 2016 | DOI: 10.1111/mmi.13312

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      The nucleotide phosphatase PapP was reported to play an important role in virulence of Streptococcus pneumoniae. PapP is able to hydrolyse pAp and pApA, two compounds produced during lipid biosynthesis and ci-di-AMP degradation. Deletion of papP resulted in membrane integrity alteration, morphological defects and mis-localization of cell division proteins. Furthermore, partial inactivation of lipid biosynthesis pathway phenocopied ΔpapP mutant. Taken together, the data support a role for PapP in membrane lipid homeostasis.

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