Molecular Microbiology

Cover image for Vol. 100 Issue 3

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

Edited By: John D. Helmann

Impact Factor: 4.419

ISI Journal Citation Reports © Ranking: 2014: 20/119 (Microbiology); 66/290 (Biochemistry & Molecular Biology)

Online ISSN: 1365-2958

Associated Title(s): Cellular Microbiology

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  1. 1 - 43
  1. Research Articles

    1. 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

      Article first published 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.

  2. MicroCommentary

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      A novel pathway of arsenate detoxification

      Fang-Jie Zhao

      Article first published online: 29 APR 2016 | DOI: 10.1111/mmi.13395

  3. Research Articles

    1. Synergistic interaction of glyceraldehydes-3-phosphate dehydrogenase and ArsJ, a novel organoarsenical efflux permease, confers arsenate resistance

      Jian Chen, Masafumi Yoshinaga, Luis D. Garbinski and Barry P. Rosen

      Article first published online: 20 APR 2016 | DOI: 10.1111/mmi.13371

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      We identified a new pathway of arsenate resistance involving biosynthesis and extrusion of an unusual pentavalent organoarsenical, 1As3PGA, synthesized by glyceraldehyde-3-phosphate dehydrogenase. ArsJ is an efflux permease that extrudes 1As3PGA from cells, where it rapidly dissociates, creating a novel pathway of arsenate resistance.

  4. MicroCommentary

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  5. Research Articles

    1. 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

      Article first published 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.

    2. 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

      Article first published 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.

    3. 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

      Article first published 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.

    4. The CpxRA two-component system contributes to Legionella pneumophila virulence

      Jennifer R. Tanner, Laam Li, Sébastien P. Faucher and Ann Karen C. Brassinga

      Article first published online: 20 APR 2016 | DOI: 10.1111/mmi.13365

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      Overview of the CpxRA regulon and its role in L. pneumophila virulence. We identified the CpxRA system to be essential for survival in protozoa, but not in human macrophages. Expression of cpxRA, genetically organized in an operon structure with three other genes lpg1439-1441, is subjected to positive autoregulation and negative regulation by an unknown factor. Transcriptomic analyses expanded the list of CpxRA regulon members to include Type II secretion system substrates and additional Dot/Icm effectors.

    5. A Trichoderma atroviride stress-activated MAPK pathway integrates stress and light signals

      Edgardo Ulises Esquivel-Naranjo, Mónica García-Esquivel, Elizabeth Medina-Castellanos, Víctor Alejandro Correa-Pérez, Jorge Luis Parra-Arriaga, Fidel Landeros-Jaime, José Antonio Cervantes-Chávez and Alfredo Herrera-Estrella

      Article first published online: 20 APR 2016 | DOI: 10.1111/mmi.13355

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      Cells possess stress-activated signalling pathways, which are activated practically in response to any cellular insult, regulating responses for survival and adaptation to harmful environmental changes. We show that one such pathway (SAPK) of T. atroviride, controls response to osmotic and oxidative stress, cell wall damage, high temperature, cadmium, UV irradiation, and development. Strikingly, light stimulates tolerance to osmotic stress, photoconidiation and expression of light regulated genes through this pathway.

    6. Spatiotemporal choreography of chromosome and megaplasmids in the Sinorhizobium meliloti cell cycle

      Benjamin Frage, Johannes Döhlemann, Marta Robledo, Daniella Lucena, Patrick Sobetzko, Peter L. Graumann and Anke Becker

      Article first published online: 20 APR 2016 | DOI: 10.1111/mmi.13351

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      A considerable share of bacterial species maintains multipartite genomes. The alpha-proteobacterium Sinorhizobium meliloti possesses a tripartite genome composed of one chromosome and the megaplasmids pSymA and pSymB. Monitoring the spatiotemporal dynamics of the origins of replication of these replicons revealed a strict temporal order of segregation events commencing with the chromosome followed by pSymA and then by pSymB.

    7. 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

      Article first published 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

    8. Suppression of a deletion mutation in the gene encoding essential PBP2b reveals a new lytic transglycosylase involved in peripheral peptidoglycan synthesis in Streptococcus pneumoniae D39

      Ho-Ching Tiffany Tsui, Jiaqi J. Zheng, Ariel N. Magallon, John D. Ryan, Rachel Yunck, Britta E. Rued, Thomas G. Bernhardt and Malcolm E. Winkler

      Article first published online: 15 APR 2016 | DOI: 10.1111/mmi.13366

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      An endo-lytic transglycosylase, named MltGSpn, is reported as a new component of the peripheral (side-wall-like) peptidoglycan (PG) synthesis machine in the ovococcus pathogen, Streptococcus pneumoniae. ‘Synthetic viable’ combinations of null mutations and a single MltG(Y488D) change suppress the requirement for the essential PBP2b, MreCD, RodZ and RodA proteins and suggest a genetic interaction between PBP2b and RodA. A model is proposed in which MltG releases newly synthesized glycan chains for crosslinking in peripheral PG synthesis.

    9. The Listeria monocytogenes Fur-regulated virulence protein FrvA is an Fe(II) efflux P1B4-type ATPase

      Hualiang Pi, Sarju J. Patel, José M. Argüello and John D. Helmann

      Article first published online: 14 APR 2016 | DOI: 10.1111/mmi.13368

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      We demonstrate that the Listeria monocytogenes Fur-regulated virulence gene frvA encodes a P1B4-type Fe(II) efflux ATPase orthologous to Bacillus subtilis PfeT. FrvA is induced by Fur in response to iron excess and mutants lacking frvA are iron sensitive. Expression of FrvA in B. subtilis depletes cells of iron leading to derepression of both Fur- and PerR-regulated genes.

    10. You have full text access to this OnlineOpen article
      Conditional gene deletion with DiCre demonstrates an essential role for CRK3 in Leishmania mexicana cell cycle regulation

      Samuel M. Duncan, Elmarie Myburgh, Cintia Philipon, Elaine Brown, Markus Meissner, James Brewer and Jeremy C. Mottram

      Article first published online: 13 APR 2016 | DOI: 10.1111/mmi.13375

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      Many protein kinases are essential post-transcriptional regulators of cell cycle and life cycle progression in Leishmania. To investigate their function, we have developed a conditional method for deletion of essential genes, based on diCre-lox mediated excision, which we have applied to the cdc2-related protein kinase CRK3. We demonstrate that CRK3 activity is essential for cell cycle progression through mitosis, and show that conditional deletion of the gene in mammalian infectious L. mexicana promastigotes prevents proliferation in a murine model of infection.

    11. Structural and biochemical characterization of EDTA monooxygenase and its physical interaction with a partner flavin reductase

      Se-Young Jun, Kevin M. Lewis, Buhyun Youn, Luying Xun and ChulHee Kang

      Article first published online: 13 APR 2016 | DOI: 10.1111/mmi.13363

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      EDTA is the most abundant organic pollutant due to its recalcitrance and extensive use. EDTA monooxygenase (EmoA) is an FMNH2-dependent enzyme that requires EmoB to provide FMNH2 for the conversion of EDTA to ED3A and EDDA. The crystal structures, thermodynamics and kinetic studies reveal its dimeric nature, catalytic mechanism, and physical interaction with EmoB. Enhanced activities of both EmoA and EmoB are observed, which might be due to a coupled channeling of FMNH2.

    12. Homologous regulators, CnfR1 and CnfR2, activate expression of two distinct nitrogenase gene clusters in the filamentous cyanobacterium Anabaena variabilis ATCC 29413

      Brenda S. Pratte and Teresa Thiel

      Article first published online: 6 APR 2016 | DOI: 10.1111/mmi.13370

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      In the cyanobacterium Anabaena variabilis two Mo-nitrogenase gene clusters, nif1 and nif2, function in two different cell types. Little is known about factors that regulate transcription from the single promoter that drives transcription of each of these two large gene clusters. Putative regulatory proteins, CnfR1 and CnfR2, both members of a homologous group of proteins with a ferredoxin-like domain that is conserved in nitrogen-fixing cyanobacteria, activate expression of nif1 and nif2, respectively.

    13. Fine-tuning of choline metabolism is important for pneumococcal colonization

      Calum Johnston, Christoph Hauser, Peter W.M. Hermans, Bernard Martin, Patrice Polard, Hester J. Bootsma and Jean-Pierre Claverys

      Article first published online: 6 APR 2016 | DOI: 10.1111/mmi.13360

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      The human pathogen Streptococcus pneumoniae has a strict requirement for choline, the import and metabolism of which is ensured by products of the lic1 and lic2 operons. Here we uncover a complex regulatory mechanism controlling the CiaR-dependent Plic1P1 promoter, resulting in its induction upon choline depletion. This regulation allows rapid response to fluctuating choline levels to maximize choline metabolism in harsh environments and is shown to be important for pneumococcal colonization.

    14. Autoregulation of the tufB operon in Salmonella

      Gerrit Brandis, Jessica M. Bergman and Diarmaid Hughes

      Article first published online: 5 APR 2016 | DOI: 10.1111/mmi.13364

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      The amount of EF-Tu expressed from tufB can vary two-fold but the mechanism of this regulation is unknown. Based on analysis of selected and constructed mutations, and using transcriptional and translational fusions, we propose a model where translational speed is used as a sensor for EF-Tu concentration and where the expression of tufB is post-transcriptionally regulated. This model describes for the first time how expression of the most abundant Salmonella protein is autoregulated.

    15. 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

      Article first published 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.

    16. Mycobacterium tuberculosis RuvX is a Holliday junction resolvase formed by dimerisation of the monomeric YqgF nuclease domain

      Astha Nautiyal, P. Sandhya Rani, Gary J. Sharples and K. Muniyappa

      Article first published online: 1 APR 2016 | DOI: 10.1111/mmi.13338

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      Mycobacterium tuberculosis genome possesses homologues of the ruvC and ruvX (yqgF) genes that encode putative Holliday junction (HJ) resolvases. However, their enzymatic properties have not been experimentally defined. This work reveals that although both MtRuvC and MtRuvX cleaved HJ, the latter displayed robust HJ resolution activity. Strikingly, we found that disulfide-bond mediated dimerization is essential for MtRuvX activity. This is the first example of a Holliday junction resolvase requiring inter-molecular disulfide-bond formation for biological activity.

    17. Polypeptide release factors and stop codon recognition in the apicoplast and mitochondrion of Plasmodium falciparum

      Suniti Vaishya, Vikash Kumar, Ankit Gupta, Mohammad Imran Siddiqi and Saman Habib

      Article first published online: 30 MAR 2016 | DOI: 10.1111/mmi.13369

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      Partitioning of nuclear-encoded release factors that recognize stop-codons for peptide release in organelles of the malaria parasite was determined. A single RF1 and a single RF2 target to the mitochondrion and apicoplast, respectively to recognize the UAA codons that terminate protein synthesis in the former and the UAA and UGA codons in the latter. A non-canonical RF, ICT1, also partitions to the mitochondrion and mediates codon nonspecific peptide release.

    18. BsdABsd2-dependent vacuolar turnover of a misfolded version of the UapA transporter along the secretory pathway: prominent role of selective autophagy

      Minoas Evangelinos, Olga Martzoukou, Koar Chorozian, Sotiris Amillis and George Diallinas

      Article first published online: 28 MAR 2016 | DOI: 10.1111/mmi.13358

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      A misfolded version of UapA transporter (ΔR481) partially escapes ERAD and is degraded in vacuoles via a non-endocytic pathway. ΔR481 vacuolar degradation is dependent on its interaction with the BsdA ER-adaptor of HulA ubiquitin ligase. Selective autophagy is shown to be the primary mechanism for ΔR481 vacuolar degradation, although degradation can also take place via Golgi traffic in autophagy deficient mutants. In conclusion, multiple overlapping turnover mechanisms seem to detoxify A. nidulans from misfolded transporters.

    19. Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence

      Ariane Cristina Mendes de Oliveira Bruder Nascimento, Thaila Fernanda dos Reis, Patrícia Alves de Castro, Juliana I. Hori, Vinícius Leite Pedro Bom, Leandro José de Assis, Leandra Naira Zambelli Ramalho, Marina Campos Rocha, Iran Malavazi, Neil Andrew Brown, Vito Valiante, Axel A. Brakhage, Daisuke Hagiwara and Gustavo H. Goldman

      Article first published online: 23 MAR 2016 | DOI: 10.1111/mmi.13354

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      We investigated which stress responses were influenced by the MpkC and SakA mitogen-activated protein (MAP) kinases of the high-osmolarity glycerol (HOG) pathway in the fungal pathogen Aspergillus fumigatus. The ΔsakA and the double ΔmpkC ΔsakA mutants were more sensitive to osmotic and oxidative stresses, and to cell wall damaging agents. A. fumigatus ΔsakA and ΔmpkC were virulent in mouse survival experiments. In contrast, the ΔmpkC ΔsakA double mutant showed highly attenuated virulence. We propose that both Cell Wall Integrity (CWI) and HOG pathways collaborate, and that MpkC could act by modulating SakA activity upon exposure to several types of stresses and during cell wall biosynthesis.

    20. A novel regulator controls Clostridium difficile sporulation, motility and toxin production

      Adrianne N. Edwards, Rita Tamayo and Shonna M. McBride

      Article first published online: 22 MAR 2016 | DOI: 10.1111/mmi.13361

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      Although sporulation is critical for Clostridium difficile survival outside of the host, little is known about the regulatory factors that govern early sporulation events. This study describes a novel, bifunctional protein, named RstA, which positively controls sporulation while decreasing toxin production, motility and virulence. The gene encoding RstA is conserved in several clostridial organisms, suggesting that RstA may direct sporulation and virulence in several important, endospore-forming pathogens.

    21. Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation

      Jorge Ripoll-Rozada, Yolanda García-Cazorla, María Getino, Cristina Machón, David Sanabria-Ríos, Fernando de la Cruz, Elena Cabezón and Ignacio Arechaga

      Article first published online: 22 MAR 2016 | DOI: 10.1111/mmi.13359

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      Antibiotic resistance is an emergent threat to human health. Bacterial conjugation is the main mechanism for the wide spread dissemination of antibiotic resistance genes. Here, we found that conjugative traffic ATPases are the molecular target for the inhibition of conjugation by unsaturated fatty acids. Identification of this molecular target will provide us with a new tool for the rational design of more potent and efficient drugs to stop the transmission of antibiotic resistance genes.

    22. Revisiting the cell biology of the acyl-ACP:phosphate transacylase PlsX suggests that the phospholipid synthesis and cell division machineries are not coupled in Bacillus subtilis

      Diego Emiliano Sastre, Alexandre Bisson-Filho, Diego de Mendoza and Frederico J. Gueiros-Filho

      Article first published online: 22 MAR 2016 | DOI: 10.1111/mmi.13337

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      We have re-investigated the localization of PlsX, a central enzyme in phospholipid synthesis of Bacillus subtilis. We determined that PlsX is uniformly distributed on the membrane of cells, but occasionally appears as motile membrane foci as well. PlsX does not colocalize with the divisome and the depletion of PlsX does not affect Z-ring formation if phospholipid synthesis is maintained. Thus, coordination between membrane synthesis and cell division may not involve an interaction between both machineries.

    23. The roles of the hybrid cluster protein, Hcp and its reductase, Hcr, in high affinity nitric oxide reduction that protects anaerobic cultures of Escherichia coli against nitrosative stress

      Jing Wang, Claire E. Vine, Basema K. Balasiny, John Rizk, Charlene L. Bradley, Mariana Tinajero-Trejo, Robert K. Poole, Linda L. Bergaust, Lars R. Bakken and Jeffrey A. Cole

      Article first published online: 22 MAR 2016 | DOI: 10.1111/mmi.13356

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      The hybrid cluster protein, Hcp, contains a unique 4Fe-2S-2O iron-sulfur-oxygen cluster. Hcp protects various bacteria from nitrosative stress, but the mechanism is unknown. We demonstrate that the Escherichia coli Hcp is a high affinity nitric oxide (NO) reductase that is the major enzyme for reducing NO stoichiometrically to N2O, but only under physiologically relevant conditions of submicromolar [NO].

    24. Novobiocin binding to NalD induces the expression of the MexAB-OprM pump in Pseudomonas aeruginosa

      Weizhong Chen, Dan Wang, Wenquan Zhou, Hong Sang, Xichun Liu, Zhiyun Ge, Jin Zhang, Lefu Lan, Cai-Guang Yang and Hao Chen

      Article first published online: 16 MAR 2016 | DOI: 10.1111/mmi.13346

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      NalD is the secondary repressor of the MexAB-OprM multidrug efflux pump, the major system contributing to intrinsic multidrug resistance in Pseudomonas aeruginosa. We identify novobiocin as binding directly to NalD, which leads NalD to dissociate from DNA promoter and thus de-represses the expression of the MexAB-OprM efflux pump.

    25. Transfer of the methicillin resistance genomic island among staphylococci by conjugation

      M. D. Ray, S. Boundy and G. L. Archer

      Article first published online: 14 MAR 2016 | DOI: 10.1111/mmi.13340

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      SCCmec, the genomic island containing the gene that encodes methicillin resistance, was captured on a conjugative plasmid by recombination at IS elements and transferred by conjugation between different Staphylococcus aureus sequence types and between S. aureus and Staphylococcus epidermidis. In some of the recipients SCCmec excised from the plasmid and inserted site-specifically into the recipient chromosome. This is the first demonstration of a mechanism for the interspecies dissemination of methicillin resistance among staphylococci.

    26. Alarmone (p)ppGpp regulates the transition from pathogenicity to mutualism in Photorhabdus luminescens

      Ragnhild Bager, Mohammad Roghanian, Kenn Gerdes and David J. Clarke

      Article first published online: 11 MAR 2016 | DOI: 10.1111/mmi.13345

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      Photorhabdus luminescens is an enterobacterium that is highly virulent to insects whilst also maintaining a mutualistic association with nematodes from the family Heterorhabditis. We have identified the alarmone (p)ppGpp as a key regulator of the transition from pathogenicity to mutualism in P. luminescens. We determined that (p)ppGpp is not required for pathogenicity but is essential for bacterial secondary metabolism, and for the ability of the bacteria to support normal nematode growth and development.

    27. The phosphocarrier protein HPr of Neisseria meningitidis interacts with the transcription regulator CrgA and its deletion affects capsule production, cell adhesion, and virulence

      Meriem Derkaoui, Ana Antunes, Sandrine Poncet, Jamila Nait Abdallah, Philippe Joyet, Alain Mazé, Céline Henry, Muhamed-Kheir Taha, Josef Deutscher and Ala-Eddine Deghmane

      Article first published online: 10 MAR 2016 | DOI: 10.1111/mmi.13349

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      The Neisseria meningitidis crgA gene (contact-regulated gene A) encodes a LysR type transcription regulator, which inhibits its own expression, but stimulates that of the upstream gene mdaB and of pilE. The phosphocarrier protein HPr and its two phospho-forms bind to CrgA and enhance its affinity for its operator (contact regulatory element of Neisseria, CREN) preceding crgA and pilE. The signal triggering the CrgA/HPr interaction is not known yet, but might be a metabolite/second messenger.

    28. Anatomy of the bacitracin resistance network in Bacillus subtilis

      Jara Radeck, Susanne Gebhard, Peter Shevlin Orchard, Marion Kirchner, Stephanie Bauer, Thorsten Mascher and Georg Fritz

      Article first published online: 10 MAR 2016 | DOI: 10.1111/mmi.13336

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      The bacitracin resistance network of Bacillus subtilis consists of two interdependent lines of defense. The primary, drug-sensing layer of resistance is provided by the bacitracin-specific ABC transporter BceAB. Its activity directly influences the response behavior of the secondary, damage sensing layer (BcrC, LiaIH). The observed compensatory regulation between these two layers results in an active redundancy within the bacitracin resistance network that can also be found in other antibiotic resistance networks.

    29. The cystathionine-β-synthase domains on the guanosine 5′’-monophosphate reductase and inosine 5′-monophosphate dehydrogenase enzymes from Leishmania regulate enzymatic activity in response to guanylate and adenylate nucleotide levels

      Sabrina Smith, Jan Boitz, Ehzilan Subramanian Chidambaram, Abhishek Chatterjee, Maria Ait-Tihyaty, Buddy Ullman and Armando Jardim

      Article first published online: 10 MAR 2016 | DOI: 10.1111/mmi.13352

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      The cystathionine-β-synthase domains on the guanosine 5′-monophosphate reductase and inosine 5′-monophosphate dehydrogenase enzymes from Leishmania regulate enzymatic activity in response to guanylate and adenylate nucleotide levels

    30. 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

      Article first published 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.

    31. Signaling by the heavy-metal sensor CusS involves rearranged helical interactions in specific transmembrane regions

      Danny Ka Chun Fung, Yongzheng Ma, Tingying Xia, Jakson Chak Hon Luk and Aixin Yan

      Article first published online: 10 MAR 2016 | DOI: 10.1111/mmi.13348

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      Signal transduction of bacterial two-component systems (TCSs) depends on the proper coupling of signal sensing to response output across biological membranes. Here we show that activation of the CusS sensor histidine kinase (HK) of the CusSR TCS is mediated by the dissociation of a transmembrane (TM) intra-molecular constraint containing T17 in TM1 and V202 in TM2. Conservancy of this TM helical interface suggested that it represents a common cross-membrane signal transduction mechanism in the heavy metal sensing TCSs.

    32. Staphylococcus aureus lactate- and malate-quinone oxidoreductases contribute to nitric oxide resistance and virulence

      Nicole A. Spahich, Nicholas P. Vitko, Lance R. Thurlow, Brenda Temple and Anthony R. Richardson

      Article first published online: 2 MAR 2016 | DOI: 10.1111/mmi.13347

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      The ability of Staphylococcus aureus to replicate in the presence of host immune effectors such as nitric oxide (NO) contributes to the high virulence potential of this bacterium. Here, we characterize a metabolic scheme employed by S. aureus undergoing moderate NO-stress whereby the combined use of lactate and peptides allows S. aureus to thrive during infection. This scheme requires both Mqo and Lqo, the founding members of a family of staphylococcal 2-hydroxyacid-quinone oxidoreductases.

    33. The signal peptide peptidase SppA is involved in sterol regulatory element-binding protein cleavage and hypoxia adaptation in Aspergillus nidulans

      Chinbayar Bat-Ochir, Jun-Yong Kwak, Sun-Ki Koh, Mee-Hyang Jeon, Dawoon Chung, Yin-Won Lee and Suhn-Kee Chae

      Article first published online: 2 MAR 2016 | DOI: 10.1111/mmi.13341

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      A finely orchestrated process is required for cleavage-activation of an endoplasmic reticulum (ER)-tethered transcription factor sterol regulatory element-binding protein (SREBP) SrbA for hypoxia adaptation in Aspergillus species. An ER-localized signal peptide peptidase SppA was newly identified as a protease for sequential cleavage of SrbA preceded by Dsc ubiquitin E3 ligase complex-linked proteolysis. Given SppA belongs to the intramembranous cleaving proteases (I-CLiPs), this study provides new insights into regulated intramembrane proteolysis (RIP) for fungal SREBP processing.

    34. A streptococcal NRAMP homologue is crucial for the survival of Streptococcus agalactiae under low pH conditions

      Sarah Shabayek, Richard Bauer, Stefanie Mauerer, Boris Mizaikoff and Barbara Spellerberg

      Article first published online: 29 FEB 2016 | DOI: 10.1111/mmi.13335

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      Group B Streptococci are human commensals capable of causing neonatal sepsis, pneumonia and meningitis. Maternal vaginal carriage is the most important risk factor for neonatal disease. In eukaryotes, the Natural Resistance-Associated Macrophage Protein (NRAMP) functions as a divalent cation transporters for Fe2+ and Mn2+ and confers on macrophages the ability to control replication of bacterial pathogens. Here we describe for first time, a pH-regulated NRAMP transporter in GBS, designated MntH, as an important colonization determinant for GBS as it helps bacteria to adapt the harsh acidic environments, facilitates bacterial adherence, contributes to the coexistence with the vaginal microbiota and plays a role in GBS survival inside macrophages.

    35. Streptomyces coelicolor XdhR is a direct target of (p)ppGpp that controls expression of genes encoding xanthine dehydrogenase to promote purine salvage

      Smitha Sivapragasam and Anne Grove

      Article first published online: 29 FEB 2016 | DOI: 10.1111/mmi.13342

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      Xanthine dehydrogenase (Xdh) functions in purine salvage pathways by converting hypoxanthine to xanthine, thereby favoring GTP synthesis. In S. coelicolor, the genes encoding Xdh are regulated by XdhR. We show that XdhR is a direct target of (p)ppGpp, which is a signaling molecule derived from GTP that accumulates during stress and starvation. We suggest that expression of xdhABC is upregulated by (p)ppGpp to promote purine salvage pathways and maintain GTP homeostasis.

    36. The toxin GraT inhibits ribosome biogenesis

      Andres Ainelo, Hedvig Tamman, Margus Leppik, Jaanus Remme and Rita Hõrak

      Article first published online: 26 FEB 2016 | DOI: 10.1111/mmi.13344

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      We report on ribosome biogenesis as a novel target of toxin-antitoxin systems. The toxin GraT of the GraTA module from Pseudomonas putida causes a processing defect of pre-rRNA and an accumulation of assembly-defective ribosome subunits. The findings that a C-terminal truncation of the chaperone DnaK can suppress the GraT-mediated ribosome maturation defect and that GraT can interact with DnaK suggest that GraT toxicity to ribosome biogenesis involves toxin interaction with DnaK.

    37. The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli

      Manon Morin, Delphine Ropers, Fabien Letisse, Sandrine Laguerre, Jean-Charles Portais, Muriel Cocaign-Bousquet and Brice Enjalbert

      Article first published online: 26 FEB 2016 | DOI: 10.1111/mmi.13343

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      This work demonstrated the pivotal role of post-transcriptional regulation to shape the E. coli carbon metabolism. The CSR system was shown here to be essential for the effective functioning of the upper glycolysis mainly through its control of PfkA.

    38. Lysine acetylation of the Mycobacterium tuberculosis HU protein modulates its DNA binding and genome organization

      Soumitra Ghosh, Bhavna Padmanabhan, Chinmay Anand and Valakunja Nagaraja

      Article first published online: 22 FEB 2016 | DOI: 10.1111/mmi.13339

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      A number of small histone-like DNA binding proteins now known as nucleoid-associated proteins (NAP) organize the bacterial nucleoid. We have identified and characterized acetylation of MtHU, the major NAP in Mycobacterium tuberculosis. We show that MtHU is a substrate for Eis, an acetyltransferase previously known to acetylate aminoglycoside antibiotics. The acetylation of lysine residues of the protein alters its DNA binding and compaction ability to regulate nucleoid organization.

    39. 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

      Article first published 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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