Molecular Microbiology

Cover image for Vol. 101 Issue 5

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


  1. 1 - 47
  1. Research Articles

    1. AvaR2, a pseudo γ-butyrolactone receptor homologue from Streptomyces avermitilis, is a pleiotropic repressor of avermectin and avenolide biosynthesis and cell growth

      Jianya Zhu, Di Sun, Wenshuai Liu, Zhi Chen, Jilun Li and Ying Wen

      Version of Record online: 25 AUG 2016 | DOI: 10.1111/mmi.13479

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      The autoregulator that triggers avermectin biosynthesis in Streptomyces avermitilis is butenolide-type avenolide. We identified AvaR2, a pseudo γ-butyrolactone receptor homologue, as an important repressor of avermectin and avenolide biosynthesis and cell growth, and also as a receptor of endogenous avenolide and exogenous antibiotics. Our findings clarify and extend the regulatory mechanisms of avermectin biosynthesis, and the ecological significance of antibiotics as signals for Streptomyces interspecies communication to induce cellular responses mediated by pseudo GBL receptors.

    2. The DnaA inhibitor SirA acts in the same pathway as Soj (ParA) to facilitate oriC segregation during Bacillus subtilis sporulation

      Yi Duan, Jack D. Huey and Jennifer K. Herman

      Version of Record online: 25 AUG 2016 | DOI: 10.1111/mmi.13477

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      SirA inhibits DNA replication through interactions with DnaA Domain I; this activity is not required for oriC capture. SirA targets DnaA Domain III to maintain oriC in a state favorable for repositioning. In Model I, Soj acts upstream of SirA, generating a conformation of DnaA favorable for SirA association. The association of SirA with DnaA Domain III then permits oriC repositioning. In Model II, Soj acts downstream of SirA to facilitate oriC capture. Model I does not exclude the possibility that Soj may also be required to facilitate oriC capture through an independent, downstream mechanism (open arrow). During Bacillus subtilis sporulation, SirA inhibits new rounds of DNA replication by interacting directly with DnaA Domain I. Through an independent function, SirA facilitates Soj(ParA)-dependent oriC segregation, thus ensuring oriC is captured on the forespore side of the septum following polar division.

    3. Functional characterization of the Aspergillus nidulans glucosylceramide pathway reveals that LCB Δ8-desaturation and C9-methylation are relevant to filamentous growth, lipid raft localization and Psd1 defensin activity

      C. M. Fernandes, P. A. de Castro, A. Singh, F. L. Fonseca, M. D. Pereira, T. V. M. Vila, G. C. Atella, S. Rozental, M. Savoldi, M. Del Poeta, G. H. Goldman and E. Kurtenbach

      Version of Record online: 25 AUG 2016 | DOI: 10.1111/mmi.13474

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      Δ4,Δ8-9,Me-glucosylceramide (GlcCer) is a fungal specific sphingolipid, contributing to growth and virulence. Aspergillus nidulans strains lacking genes involved in GlcCer synthesis (sdeA – sphingolipid Δ8-desaturase, smtA and smtB – sphingolipid C9-methyltransferase and gcsA – glucosylceramide synthase) were constructed and characterized. The accumulation of Δ4-GlcCer, Δ8-Cer and Δ4,Δ8-9,Me-Cer intermediates in ΔsdeA, ΔsmtA niiA::smtB and ΔgcsA mutants compromised growth, suggesting that fungal GlcCer structure specificities and synthesis are relevant for A. nidulans differentiation.

    4. The small membrane protein MgrB regulates PhoQ bifunctionality to control PhoP target gene expression dynamics

      Michael E. Salazar, Anna I. Podgornaia and Michael T. Laub

      Version of Record online: 25 AUG 2016 | DOI: 10.1111/mmi.13471

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      The two-component signaling pathway PhoQ-PhoP exhibits partial adaptation as target genes are initially induced to a maximal level, before decreasing to a level between that of the initial and maximal levels. We show that partial adaptation arises through a negative feedback loop involving the small protein MgrB. Initial activation of PhoP by PhoQ drives expression of MgrB, which then feeds back to inhibit PhoQ kinase activity, producing a partial adaptation of the signaling pathway and the PhoP regulon.

    5. The Staphylococcus aureus group II biotin protein ligase BirA is an effective regulator of biotin operon transcription and requires the DNA binding domain for full enzymatic activity

      Sarah K. Henke and John E. Cronan

      Version of Record online: 24 AUG 2016 | DOI: 10.1111/mmi.13470

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      A prior report argued that the BirA biotin protein ligase of Staphylococcus aureus would be a defective sensor of synthesis and attachment of the vitamin, biotin. We report that this protein is a fully functional sensor of biotin metabolism and that the prior report was due to artifacts of the in vitro assays utilized.

    6. Type IV-pili dependent motility is co-regulated by PilSR and PilS2R2 two-component systems via distinct pathways in Myxococcus xanthus

      Daniel J. Bretl, Susanne Müller, Kayla M. Ladd, Samantha N. Atkinson and John R. Kirby

      Version of Record online: 23 AUG 2016 | DOI: 10.1111/mmi.13445

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      M. xanthus uses two signaling pathways (PilSR and PilS2R2) to regulate production of Type IV pili. Uniquely, PilS2R2 regulates the production of outer membrane vesicle chains. These extracellular structures have important functions in M. xanthus motility, biofilm formation and predation.

    7. TbLOK1/ATOM19 is a novel subunit of the noncanonical mitochondrial outer membrane protein translocase of Trypanosoma brucei

      Silvia Desy, Jan Mani, Anke Harsman, Sandro Käser and André Schneider

      Version of Record online: 18 AUG 2016 | DOI: 10.1111/mmi.13476

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      The parasitic protozoan Trypanosoma brucei has an unusual mitochondrial outer membrane protein translocase termed the ATOM complex. Here we show that the previously characterized mitochondrial morphology factor TbLOK1 is a novel essential subunit of the ATOM complex. It has therefore be renamed ATOM19. Unlike any other subunits of the mitochondrial outer membrane translocase in any organism ATOM19 contains two predicted transmembrane domains.

    8. PfRH2b specific monoclonal antibodies inhibit merozoite invasion

      Yaw Aniweh, Xiaohong Gao, Karthigayan Gunalan and Peter R. Preiser

      Version of Record online: 18 AUG 2016 | DOI: 10.1111/mmi.13468

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      PfRH2b bound to its receptor triggers the merozoite intracellular Ca2+ signalling, followed by EBA175 surface expression and leads to the successful invasion.

    9. Lactic acid bacteria differentially regulate filamentation in two heritable cell types of the human fungal pathogen Candida albicans

      Weihong Liang, Guobo Guan, Yu Dai, Chengjun Cao, Li Tao, Han Du, Clarissa J. Nobile, Jin Zhong and Guanghua Huang

      Version of Record online: 18 AUG 2016 | DOI: 10.1111/mmi.13475

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      Candida albicans and Lactobacillus species (LAB) are common members of the human microbiota. Lactic acid produced by LAB plays a distinct role in the regulation of filamentation in white and opaque cells of C. albicans. The cAMP signaling pathway and transcription factors Rfg1, Cup9, and Nrg1 play a major role in this regulation.

    10. RepB proteins of the multipartite Rhizobium leguminosarum bv. trifolii genome discriminate between centromere-like parS sequences for plasmid segregational stability

      Piotr Koper, Kamil Żebracki, Małgorzata Marczak, Anna Skorupska and Andrzej Mazur

      Version of Record online: 18 AUG 2016 | DOI: 10.1111/mmi.13472

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      Stable coexistence of several plasmids equipped with similar repABC replication systems in the multipartite bacterial genome is achieved by specific interaction of centromere binding proteins (CBP) RepB with parS sites. RepB are able to discriminate between parental and non-parental parS sites thus preventing partition proteins from confusing and mis-segregation of several replicons. This specificity is further supported by sequence divergence of individual RepB and respective parS sites, which help to minimize possibility of heterologous interactions.

    11. ManLMN is a glucose transporter and central metabolic regulator in Streptococcus pneumoniae

      Eleanor Fleming and Andrew Camilli

      Version of Record online: 18 AUG 2016 | DOI: 10.1111/mmi.13473

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      During colonization and invasive disease, fermentation of host-derived carbohydrates likely represents the primary mode of energy generation for Streptococcus pneumoniae. Despite encoding 29 predicted carbohydrate transporters, we found a single PTS, ManLMN, to be essential for growth on five nonpreferred carbohydrates. Further examination revealed that ManLMN is also required for induction of some nonpreferred carbohydrate utilization genes, carbon catabolite repression and transport of glucose in some conditions.

    12. Opposing PKA and Hog1 signals control the post-transcriptional response to glucose availability in Cryptococcus neoformans

      Dithi Banerjee, Amanda L. M. Bloom and John C. Panepinto

      Version of Record online: 11 AUG 2016 | DOI: 10.1111/mmi.13461

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      Glucose is limiting in the pulmonary compartment, but upon dissemination to the CNS, C. neoformans encounters increased glucose concentrations. Here, we report that glucose availability controls ribosome biogenesis and translation by modulating mRNA decay through a balance of signaling through PKA and Hog1.

  2. MicroReviews

    1. You have free access to this content
      Intertwining nutrient-sensory networks and the control of antibiotic production in Streptomyces

      Mia Urem, Magdalena A. Świątek-Połatyńska, Sébastien Rigali and Gilles P. van Wezel

      Version of Record online: 9 AUG 2016 | DOI: 10.1111/mmi.13464

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      Streptomycetes are prolific producers of antibiotics and other natural products, but many biosynthetic gene clusters are silent under standard laboratory conditions. In this review, we look into the global nutrient sensory networks that control antibiotic biosynthetic pathways in Streptomyces, and highlight cross-talk between different pleiotropic regulators. Approaches to harness this information to activate the production of silent antibiotics are discussed.

  3. Research Articles

    1. Spirochetes flagellar collar protein FlbB has astounding effects in orientation of periplasmic flagella, bacterial shape, motility, and assembly of motors in Borrelia burgdorferi

      Ki Hwan Moon, Xiaowei Zhao, Akarsh Manne, Juyu Wang, Zhou Yu, Jun Liu and Md A. Motaleb

      Version of Record online: 9 AUG 2016 | DOI: 10.1111/mmi.13463

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      Spirochetes possess a unique periplasmic flagellar structure called collar that is absent from all externally flagellated bacteria studied to-date. Here, we show for the first time that FlbB assembles around the flagellar basal body and plays important roles in collar assembly.

    2. Invasion of hepatocytes by Plasmodium sporozoites requires cGMP-dependent protein kinase and calcium dependent protein kinase 4

      K. Govindasamy, S. Jebiwott, D. K. Jaijyan, A. Davidow, K. K. Ojo, W. C. Van Voorhis, M. Brochet, O. Billker and P. Bhanot

      Version of Record online: 9 AUG 2016 | DOI: 10.1111/mmi.13466

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      Malaria infection begins with the injection of Plasmodium sporozoites into humans by a feeding mosquito. We demonstrate that two parasite kinases, PKG and CDPK4 are crucial for sporozoite motility and consequently their entry into hepatocytes. Our results have implications for understanding the role of second messenger molecules, cGMP and Ca2+ in regulating the exo-erythrocytic cycle of Plasmodium.

  4. MicroReviews

    1. Flying under the radar: The non-canonical biochemistry and molecular biology of petrobactin from Bacillus anthracis

      A.K. Hagan, P.E. Carlson Jr and P.C. Hanna

      Version of Record online: 9 AUG 2016 | DOI: 10.1111/mmi.13465

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      This review aims to discuss the current state of knowledge regarding petrobactin use by the pathogen Bacillus anthracis. Used to gather iron during infections, petrobactin differs from other siderophores in a number of ways including: regulation, biosynthesis, structure, and transport. We argue that these differences enhance the pathogenic ability of B. anthracis through increased iron acquisition, and identify areas needing further research.

  5. Research Articles

    1. You have full text access to this OnlineOpen article
      Phytohormone sensing in the biotrophic fungus Ustilago maydis – the dual role of the transcription factor Rss1

      Franziska Rabe, Denise Seitner, Lisa Bauer, Fernando Navarrete, Angelika Czedik-Eysenberg, Fernando A. Rabanal and Armin Djamei

      Version of Record online: 8 AUG 2016 | DOI: 10.1111/mmi.13460

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      The biotrophic plant pathogenic fungus Ustilago maydis senses salicylic acid (SA), a major phytohormone. Here we identified one factor important for this process – the binuclear zinc cluster transcription factor Rss1. Rss1 is activated by SA and anthranilic acid and it regulates genes for SA as well as tryptophan degradation during biotrophic growth. However, Rss1 seems to be dispensable for virulence. Our data suggests the presence of redundant pathways that regulate SA-responsive genes during pathogenic development.

    2. Structural stability of flagellin subunit affects the rate of flagellin export in the absence of FliS chaperone

      Yukio Furukawa, Yumi Inoue, Aya Sakaguchi, Yoko Mori, Takuma Fukumura, Tomoko Miyata, Keiichi Namba and Tohru Minamino

      Version of Record online: 2 AUG 2016 | DOI: 10.1111/mmi.13469

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      FliS acts as a flagellar type III export chaperone specific for flagellin FliC. A fliS null mutant produces much shorter flagellar filaments than wild-type cells. Here, we show that the ΔfliS bypass mutations in FliC reduce the structural stability of FliC, probably for more efficient unfolding and export of FliC by the flagellar type III export apparatus in the absence of FliS.

    3. tRNAPro-mediated downregulation of elongation factor P is required for mgtCBR expression during Salmonella infection

      Daesil Nam, Eunna Choi, Dongwoo Shin and Eun-Jin Lee

      Version of Record online: 2 AUG 2016 | DOI: 10.1111/mmi.13454

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      Salmonella enterica serovar Typhimurium decreases the levels of elongation factor P during course of infection, which are mediated by low levels of charged tRNAPro. The decrease of EF-P levels is required for selective induction of the mgtC virulence gene and Salmonella's survival inside macrophages. Low levels of EF-P induce ribosome stalling at the consecutive proline codons of the short open reading frame mgtP in the mgtCBR leader, promoting mgtC expression.

    4. The protein acyltransferase Pat post-transcriptionally controls HilD to repress Salmonella invasion

      Chien-Che Hung, Colleen R. Eade and Craig Altier

      Version of Record online: 2 AUG 2016 | DOI: 10.1111/mmi.13451

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      The lysine acyltransferase Pat represses Salmonella Pathogenicity Island 1 (SPI1), which is essential for this bacterial pathogen to penetrate the host intestinal epithelium. The post-transcriptional control of the SPI1 master regulator HilD is key for Pat to exert its invasion control. As chemical means to mimic the effect of Pat are known, using deacylase inhibitors, this work therefore identifies the potential of both targets and means for the control of salmonellosis.

    5. You have full text access to this OnlineOpen article
      Unstable tandem gene amplification generates heteroresistance (variation in resistance within a population) to colistin in Salmonella enterica

      Karin Hjort, Hervé Nicoloff and Dan I Andersson

      Version of Record online: 2 AUG 2016 | DOI: 10.1111/mmi.13459

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      Heteroresistance, a phenomenon where subpopulations of a bacterial isolate exhibit different susceptibilities to an antibiotic, is a growing clinical problem. Here we show that gene amplification of large chromosomal regions containing resistance genes confers a colistin heteroresistant phenotype. We propose that variability in gene copy number of resistance genes is a common explanation for the heteroresistance observed in clinically isolated bacteria.

    6. The Aspergillus fumigatus conidial melanin production is regulated by the bifunctional bHLH DevR and MADS-box RlmA transcription factors

      Vito Valiante, Clara Baldin, Peter Hortschansky, Radhika Jain, Andreas Thywißen, Maria Straßburger, Ekaterina Shelest, Thorsten Heinekamp and Axel A. Brakhage

      Version of Record online: 28 JUL 2016 | DOI: 10.1111/mmi.13462

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      The promoter region present in the DHN-melanin cluster can be specifically recognized by two transcriptional regulators belonging to the bHLH (DevR) and MADS-box MEF2-like (RlmA) families. In vitro and in vivo experiments proved that these transcription factors cooperatively regulate DHN-melanin gene expression acting both as repressors and activators in a mutually exclusive manner. In addition, the dual role executed by these regulators depends on specific DNA motifs recognized in promoter regions.

    7. Cyclic di-AMP targets the cystathionine beta-synthase domain of the osmolyte transporter OpuC

      TuAnh Ngoc Huynh, Philip H. Choi, Kamakshi Sureka, Hannah E. Ledvina, Julian Campillo, Liang Tong and Joshua J. Woodward

      Version of Record online: 26 JUL 2016 | DOI: 10.1111/mmi.13456

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      Osmoadaptation is mediated in part through the uptake of the compatible solutes carnitine and betaine. Osmotolerance is inversely correlated with the production of the nucleotide c-di-AMP in Listeria monocytogenes, which directly binds to the CBS domain of the ATPase component of the carnitine transporter OpuC. These findings expand the link between c-di-AMP production and osmoadaptation among bacteria that produce this second messenger.

    8. GerM is required to assemble the basal platform of the SpoIIIA–SpoIIQ transenvelope complex during sporulation in Bacillus subtilis

      Christopher D. A. Rodrigues, Fernando H. Ramírez-Guadiana, Alexander J. Meeske, Xindan Wang and David Z. Rudner

      Version of Record online: 22 JUL 2016 | DOI: 10.1111/mmi.13457

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      During Bacillus subtilis sporulation a multimeric membrane complex connects the mother cell and developing spore. Assembly of this complex starts with a transenvelope interaction between SpoIIQ and SpoIIIAH. SpoIIQ anchors SpoIIIAH in the septum on the mother-cell side. How SpoIIQ is targeted to the forespore septal membranes has remained unclear. Here, we identify GerM as the missing factor that localizes SpoIIQ suggesting that these three proteins constitute the basal assembly platform for this complex.

    9. RpoS-dependent sRNA RgsA regulates Fis and AcpP in Pseudomonas aeruginosa

      Pei Lu, Yifei Wang, Yong Zhang, Yangbo Hu, Karl M. Thompson and Shiyun Chen

      Version of Record online: 22 JUL 2016 | DOI: 10.1111/mmi.13458

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      RgsA is a conserved sRNA in Pseudomonas species. Two direct regulatory targets of RgsA, the mRNAs coding for the global transcriptional regulator Fis and the acyl carrier protein AcpP, were identified in P. aeruginosa. RgsA downregulates the synthesis of Fis and AcpP by base-pairing, this regulation requires the RNA chaperone protein Hfq. Our study suggests a novel regulatory role of sRNA in which the versatile transcriptional regulator Fis and the stress regulator RpoS are connected by RgsA.

    10. You have full text access to this OnlineOpen article
      The bacterial SRP receptor, FtsY, is activated on binding to the translocon

      Albena Draycheva, Thomas Bornemann, Sergey Ryazanov, Nils-Alexander Lakomek and Wolfgang Wintermeyer

      Version of Record online: 19 JUL 2016 | DOI: 10.1111/mmi.13452

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      Cotranslational membrane targeting of ribosomes by the signal recognition particle (SRP) pathway in bacteria involves an interaction of the SRP protein Ffh and the SRP receptor, FtsY, through their homologous NG domains. SRP is activated on the ribosome by exposing the NG domain. Here we show that the activation for targeting complex formation is symmetric in that the NG domain of FtsY is exposed on binding to the translocon in a phospholipid environment.

    11. R-loop induced stress response by second (p)ppGpp synthetase in Mycobacterium smegmatis: functional and domain interdependence

      Sushma Krishnan, Anushya Petchiappan, Albel Singh, Apoorva Bhatt and Dipankar Chatterji

      Version of Record online: 19 JUL 2016 | DOI: 10.1111/mmi.13453

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      Due to the presence of a RNase HII domain and a (p)ppGpp synthesizing domain together in MS_RHII-RSD, R-loops are degraded, and the interrupted RNA polymerase is destabilized by unknown mechanism to rescue the organism from replicative stress. Consistent with this observation, MS_RHII-RSD gene expression was upregulated under ultra violet (UV) stress and increased R-loop accumulation was observed in this gene deleted strain. We have further elucidated its domain dependence for the optimal protein function.

    12. Functional compartmentalization of Rad9 and Hus1 reveals diverse assembly of the 9-1-1 complex components during the DNA damage response in Leishmania

      Jeziel D. Damasceno, Ricardo Obonaga, Elaine V. Santos, Alan Scott, Richard McCulloch and Luiz R. O. Tosi

      Version of Record online: 19 JUL 2016 | DOI: 10.1111/mmi.13441

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      The Rad9-Rad1-Hus1 (9-1-1) complex is a key component of the DNA metabolism in eukaryotes. The protozoan Leishmania express a 9-1-1-homolog clamp, which associate with chromatin and participate in the cellular response to genotoxic stress. LmRad9 and LmHus1-deficient cells have opposite phenotypes. Remarkably, LmRad9 forms an alternative complex, and LmHus1 exists as a monomer. These alternative forms may mediate the observed functional compartmentalization with a direct impact on the response to genotoxic stress.

    13. The genes that encode the gonococcal transferrin binding proteins, TbpB and TbpA, are differentially regulated by MisR under iron-replete and iron-depleted conditions

      Justin L. Kandler, Rosuany Vélez Acevedo, Mary Kathryne Dickinson, Devin R. Cash, William M. Shafer and Cynthia Nau Cornelissen

      Version of Record online: 18 JUL 2016 | DOI: 10.1111/mmi.13450

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      MisR regulates expression of the gonococcal genes that encode the transferrin-binding proteins (tbpA and tbpB). Phosphorylated MisR binds to the promoter of the tbp operon. The tbp genes are down-regulated by MisR under iron-replete conditions and up-regulated by MisR under iron-depleted conditions. This is the first demonstration that the gonococcal tbp genes are controlled by a trans-acting factor in addition to Fur.

    14. You have full text access to this OnlineOpen article
      Feedback control of Campylobacter jejuni flagellin levels through reciprocal binding of FliW to flagellin and the global regulator CsrA

      Katarzyna A. Radomska, Soledad R. Ordoñez, Marc M. S. M. Wösten, Jaap A. Wagenaar and Jos P. M. van Putten

      Version of Record online: 18 JUL 2016 | DOI: 10.1111/mmi.13455

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      We discovered a novel mechanism of regulation of flagellin biosynthesis in the bacterial pathogen Campylobacter jejuni. This mechanism controls flagellin levels through interaction of the flagellin assembly factor FliW with flagellin and the global post-transcriptional regulator CsrA.

    15. Overexpression of SepJ alters septal morphology and heterocyst pattern regulated by diffusible signals in Anabaena

      Vicente Mariscal, Dennis J. Nürnberg, Antonia Herrero, Conrad W. Mullineaux and Enrique Flores

      Version of Record online: 18 JUL 2016 | DOI: 10.1111/mmi.13436

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      Overexpression of septal protein SepJ in the filamentous, heterocyst-forming cyanobacterium Anabaena alters the structure of the intercellular septa and the heterocyst pattern regulated by the PatS morphogen and a HetN-related signal. The drawings show parts of a heterocyst and adjacent vegetative cell in wild-type Anabaena (upper panel) and the SepJ overexpressing strain (lower panel). Note the different sizes of the septum in the two strains and the possible presence of a higher number of SepJ-related septal junctions (red lines) in the SepJ overexpressing strain than in the wild type.

    16. Diphosphates at the 5′ end of the positive strand of yeast L-A double-stranded RNA virus as a molecular self-identity tag

      Tsutomu Fujimura and Rosa Esteban

      Version of Record online: 15 JUL 2016 | DOI: 10.1111/mmi.13446

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      The positive strand of the yeast L-A dsRNA viral genome has mostly 5′ diphosphates. These phosphates are not only essential for the cap-snatching reaction to synthesize capped viral mRNAs, but also crucial for viral transcription. Because host cytosolic RNAs (mRNA, tRNA, and rRNA) are uniformly devoid of 5′ pp-structures, the L-A virus takes advantage of its 5′ diphosphates, using them as a self-identity tag to propagate in the host cytoplasm.

    17. You have full text access to this OnlineOpen article
      Mutational analysis of the Aspergillus ambient pH receptor PalH underscores its potential as a target for antifungal compounds

      Daniel Lucena-Agell, América Hervás-Aguilar, Tatiana Múnera-Huertas, Olga Pougovkina, Joanna Rudnicka, Antonio Galindo, Joan Tilburn, Herbert N. Arst Jr and Miguel A. Peñalva

      Version of Record online: 15 JUL 2016 | DOI: 10.1111/mmi.13438

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      Fungi colonize environments with different values of pH by adapting their patterns of gene expression to the needs imposed by ambient pH. pH regulation is important for fungal pathogenicity, but therapeutically useful drugs targeting the pH signalling pathway are yet to be developed. We show that the ascomycete ambient pH receptor PalH resembles a major class of mammalian receptors, denoted GPCRs. Thus our data pave the way for the identification of specific inhibitors of the ambient pH receptor for antifungal intervention.

    18. Comprehensive analysis of type 1 fimbriae regulation in fimB-null strains from the multidrug resistant Escherichia coli ST131 clone

      Sohinee Sarkar, Leah W. Roberts, Minh-Duy Phan, Lendl Tan, Alvin W. Lo, Kate M. Peters, David L. Paterson, Mathew Upton, Glen C. Ulett, Scott A. Beatson, Makrina Totsika and Mark A. Schembri

      Version of Record online: 15 JUL 2016 | DOI: 10.1111/mmi.13442

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      Uropathogenic E. coli ST131 strains from the globally dominant fluoroquinolone-resistant subgroup possess an ISEc55 insertion in the fimB gene that regulates fimS, an invertible DNA element containing the type 1 fimbriae promoter. Using fimbrial expression assays and a novel Illumina-based read-mapping approach, we show that fimS inversion is reduced in these strains and controlled by other recombinases. The figure highlights differences in type 1 fimbriae regulation between reference ST131 (EC958) and non-ST131 (UTI89) strains.

    19. Global Tn-seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi

      Erin B. Troy, Tao Lin, Lihui Gao, David W. Lazinski, Maureen Lundt, Andrew Camilli, Steven J. Norris and Linden T. Hu

      Version of Record online: 15 JUL 2016 | DOI: 10.1111/mmi.13437

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      This work establishes Tn-seq as a new tool for performing high-throughput genetic fitness analyses in Borrelia burgdorferi. We used the technique to perform an in vitro screen exploring mechanisms of mannose, maltose, trehalose and N-acetyl-glucosamine metabolism in B. burgdorferi as well as a complementing in vivo screen in mice. In doing so we obtained insight into the potential functions of genes annotated as encoding carbohydrate transporters and an additional function of the response regulator Rrp1.

    20. Identification of the first transcriptional activator of an archaellum operon in a euryarchaeon

      Yan Ding, John Nash, Alison Berezuk, Cezar M. Khursigara, David N. Langelaan, Steven P. Smith and Ken F. Jarrell

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/mmi.13444

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      Analysis of the complete genome sequence of a mutant of the archaeon Methanococcus maripaludis that had stopped production of components of archaella led to the identification of the first transcriptional activator, EarA, for the archaella operon in this major branch of Archaea. Cells deleted for earA do not transcribe the archaella operon and are nonarchaellated. Both in vitro and in vivo experiments demonstrate that EarA binds directly upstream of the promoter for the archaella operon.

    21. σE-dependent activation of RbpA controls transcription of the furA-katG operon in response to oxidative stress in mycobacteria

      Yangbo Hu, Zhongwei Wang, Lipeng Feng, Zhenkang Chen, Chunyou Mao, Yan Zhu and Shiyun Chen

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/mmi.13449

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      The role of RbpA and its cooperation with σ factors in response to oxidative stress in mycobacteria are investigated, and the effect of RbpA activity in modulating the mycobacterial gene transcription profile under oxidative stress is characterized. We propose that, in the presence of H2O2, σE-dependent activation of RbpA interacts with the principal sigma factor σA and controls the transcription of katG, which encodes an H2O2 scavenging enzyme to decrease the H2O2 concentration in mycobacteria.

    22. More than a hole: the holin lethal function may be required to fully sensitize bacteria to the lytic action of canonical endolysins

      Sofia Fernandes and Carlos São-José

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/mmi.13448

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      We show that bacterial cells under conditions supporting the membrane proton motive force (pmf) can counteract the lytic activity of canonical endolysins. Pmf dissipation by the holin or by ionophores mimicking its action results in drastic increase in endolysin lytic activity. Therefore, in canonical lysis the holin action may be crucial not only for endolysin transport to the cell wall, but also to turn bacteria fully susceptible to endolysin attack.

    23. Following transforming DNA in Helicobacter pylori from uptake to expression

      Christopher Corbinais, Aurélie Mathieu, Thierry Kortulewski, J. Pablo Radicella and Stéphanie Marsin

      Version of Record online: 8 JUL 2016 | DOI: 10.1111/mmi.13440

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      Helicobacter pylori, a major human pathogen at the origin of gastric ulcers and cancer, is characterised by its capacity to constitutively capture exogenous DNA and incorporate it into its genome. We have followed this process in real time by using fluorescently labelled DNA and its subsequent expression, confirming the role of ComEC for the transit of the DNA through the inner membrane.

    24. Trypanosomatid parasites rescue heme from endocytosed hemoglobin through lysosomal HRG transporters

      María Cabello-Donayre, Sophie Malagarie-Cazenave, Jenny Campos-Salinas, Francisco J. Gálvez, Alba Rodríguez-Martínez, Estela Pineda-Molina, Lina M. Orrego, Marta Martínez-García, María P. Sánchez-Cañete, Antonio M. Estévez and José M. Pérez-Victoria

      Version of Record online: 8 JUL 2016 | DOI: 10.1111/mmi.13430

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      An Achilles' heel of pathogenic trypanosomatid parasites is their absolute dependence on scavenging heme from their human hosts. Here, we unravel the mechanism used by Trypanosoma brucei (responsible for sleeping sickness) and Leishmania (leishmaniasis) to rescue heme from host hemoglobin. By using homologous and heterologous systems we show evidences strongly suggesting that parasite HRG transporters are responsible for heme transport from the endolysosomal compartment, where endocytosed hemoglobin is degraded, to the cytosol.

    25. A partial metabolic pathway enables group b streptococcus to overcome quinone deficiency in a host bacterial community

      Thierry Franza, Emilie Delavenne, Aurélie Derré-Bobillot, Vincent Juillard, Mylène Boulay, Emmanuelle Demey, Joelle Vinh, Gilles Lamberet and Philippe Gaudu

      Version of Record online: 8 JUL 2016 | DOI: 10.1111/mmi.13447

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      Group B Streptococcus (GBS) is a human commensal bacterium that can become a pathogen. In polymicrobial population, GBS is able to acquire 1,4-dihydroxy-2-naphthoic acid (DHNA) and use it to synthesize its own demethylmenaquinones (DMKs) by the IspB and MenA enzymes. DMKs are substrates of the CydAB oxidase that also requires oxygen and exogenous heme to be active. Thus, through interspecies metabolic exchanges, GBS is able to switch from fermentation towards a respiratory metabolism that increases its growth capacity and virulence in the host.

    26. Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence

      Jeongjoon Choi and Eduardo A. Groisman

      Version of Record online: 8 JUL 2016 | DOI: 10.1111/mmi.13439

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      How does an organism respond to changes in the pH of its surroundings? We now report that the sensor PhoQ from Salmonella enterica operates as a cytoplasmic pH sensor, and that its ability to sense a decrease in cytoplasmic pH is necessary for Salmonella virulence. By responding to cytoplasmic pH changes PhoQ enables S. enterica to integrate host and bacterial metabolic signals to activate a critical virulence program.

    27. Structural organization of membrane-inserted hexamers formed by Helicobacter pylori VacA toxin

      Tasia M. Pyburn, Nora J. Foegeding, Christian González-Rivera, Nathan A. McDonald, Kathleen L. Gould, Timothy L. Cover and Melanie D. Ohi

      Version of Record online: 8 JUL 2016 | DOI: 10.1111/mmi.13443

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      Helicobacter pylori colonizes the stomach and increases the risk of gastroduodenal disease in infected individuals. H. pylori VacA, a secreted toxin, forms channels in cell membranes and causes alterations in host cells. The vacA genotype of a strain correlates with the risk of H. pylori-associated gastric cancer and the various forms of VacA have different activities in vitro. We show that upon binding to membrane, monomeric VacA oligomerizes into membrane-inserted hexamers. There is a visible structural difference in the pore-forming domain of VacA when comparing soluble and membrane-bound hexamers. These results provide important new insights into mechanisms of VacA oligomerization and membrane insertion.

    28. The crystal structure of the major pneumococcal autolysin LytA in complex with a large peptidoglycan fragment reveals the pivotal role of glycans for lytic activity

      Tatyana Sandalova, Mijoon Lee, Birgitta Henriques-Normark, Dusan Hesek, Shahriar Mobashery, Peter Mellroth and Adnane Achour

      Version of Record online: 5 JUL 2016 | DOI: 10.1111/mmi.13435

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      The atomic resolution crystal structure of the S. pneumonia-associated major autolysin LytA in complex with a large peptidoglycan fragment allows for precise determination of the conformation of the substrate as well as for a thorough investigation of the role of twenty-one substrate-interacting residues within the binding crevice. The present study demonstrates that several glycan-interacting residues located outside the catalytic site play nonetheless a critical role in the lytic activity of this key bacterial enzyme.

    29. Pseudopilin residue E5 is essential for recruitment by the type 2 secretion system assembly platform

      Mangayarkarasi Nivaskumar, Javier Santos-Moreno, Christian Malosse, Nathalie Nadeau, Julia Chamot-Rooke, Guy Tran Van Nhieu and Olivera Francetic

      Version of Record online: 5 JUL 2016 | DOI: 10.1111/mmi.13432

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      The highly conserved Glu residue at position 5 (E5) in the transmembrane segments of T2SS pseudopilins and type 4 pilins is essential for fibre assembly and function. Using the bacterial two-hybrid and copurification approaches, we show that the major T2SS pseudopilin and one of four minor pseudopilins interact with the assembly platform components PulM and PulF. Residue E5 is specifically required for interactions with PulM, suggesting a role in pseudopilin recruitment to the assembly complex.

    30. Identification and functional analysis of two toxin–antitoxin systems in Campylobacter jejuni

      Zhangqi Shen, Rocky D. Patil, Orhan Sahin, Zuowei Wu, Xiao-Ying Pu, Lei Dai, Paul J. Plummer, Michael J. Yaeger and Qijing Zhang

      Version of Record online: 4 JUL 2016 | DOI: 10.1111/mmi.13431

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      Campylobacter jejuni is a major zoonotic pathogen. Here we present the first identification of toxin-antitoxin (TA) systems in this organism, which play an important role in maintaining the stability of virulence plasmid pVir. Both toxins are proteic and inhibit cell growth by degrading cellular mRNA. Antitoxin VirA neutralizes toxin VirT by protein-protein interaction, while antitoxin cjrA detoxifies toxin CjpT by binding to its mRNA.

    31. The LysR-type transcriptional regulator, CidR, regulates stationary phase cell death in Staphylococcus aureus

      Sujata S. Chaudhari, Vinai C. Thomas, Marat R. Sadykov, Jeffrey L. Bose, Daniel J. Ahn, Matthew C. Zimmerman and Kenneth W. Bayles

      Version of Record online: 4 JUL 2016 | DOI: 10.1111/mmi.13433

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      Within a developing bacterial biofilm, a subpopulation of cells undergoes cell death and release critical biofilm matrix components. Interference of such homeostatic bacterial death mechanisms hinders biofilm maturation and thus represents a potential therapeutic target. Here, we elucidate the role of various members of the CidR regulon in controlling cell death in staphylococcal populations. Notably, we demonstrate that two integral membrane proteins, CidA and CidB antithetically regulate cell death by modulating intracellular carbon partitioning into acetate and acetoin generating pathways.


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