Molecular Microbiology

Cover image for Vol. 102 Issue 2

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 - 43
  1. Research Articles

    1. ClpAP is an auxiliary protease for DnaA degradation in Caulobacter crescentus

      Jing Liu, Laura I. Francis, Kristina Jonas, Michael T. Laub and Peter Chien

      Version of Record online: 17 OCT 2016 | DOI: 10.1111/mmi.13537

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      In Caulobacter crescentus, levels of the replication initiator protein DnaA are known to be controlled through proteolysis by the Lon protease. In this work, we show that the ClpAP protease also contributes to DnaA degradation in a process inhibited by the ClpS adaptor. ClpAP degrading DnaA is particularly important during extended growth and entry into the stationary phase. Having two proteolytic pathways controlling an essential replication factor is an excellent strategy to ensure robust control under different growth conditions.

    2. Developmental change in translation initiation alters the localization of a common microbial protein necessary for Toxoplasma chronic infection

      Kathryn Milligan-Myhre, Sarah K. Wilson and Laura J. Knoll

      Version of Record online: 14 OCT 2016 | DOI: 10.1111/mmi.13538

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      A Toxoplasma mutant that is disrupted in a protein highly conserved in microbes but is not present in humans, produces fewer cysts in mouse brains during chronic infection. In cell culture, translation of this protein initiates at the third methionine to produce a 25 kDa form, whereas in brain cysts translation begins at the first methionine to produce a 51 kDa form that is secreted from the parasites and localizes to the cyst wall.

  2. MicroReview

    1. To ∼P or Not to ∼P? Non-canonical activation by two-component response regulators

      Stuti K. Desai and Linda J. Kenney

      Version of Record online: 11 OCT 2016 | DOI: 10.1111/mmi.13532

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      A majority of response regulators are activated by a phosphorylation-driven switch in response to environmental sensing by membrane-bound sensor kinases. In this microreview, we describe examples of non-canonical signaling involving unphosphorylated or unphosphorylable response regulators across bacterial phyla. Some of these non-canonical response regulators bind to silenced promoter sequences as homo or heterodimers and mediate transcriptional activation by anti-silencing.

  3. Research Articles

    1. A functional link between hyphal maintenance and quorum sensing in Candida albicans

      Melanie Polke, Marcel Sprenger, Kirstin Scherlach, María Cristina Albán-Proaño, Ronny Martin, Christian Hertweck, Bernhard Hube and Ilse D. Jacobsen

      Version of Record online: 11 OCT 2016 | DOI: 10.1111/mmi.13526

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      The deletion of the Candida albicans EED1 gene (eed1Δ), which is essential for hyphal maintenance, leads to the unique phenotype of both, an increased sensitivity to and increased production of the quorum sensing molecule farnesol. The enhanced farnesol signaling activity in eed1Δ is independent of cAMP signaling, promotes the reverse morphogenesis under hypha-inducing conditions without inducing cell death, and contributes to the hyphal maintenance defect of the mutant.

    2. The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence

      Patrícia Alves de Castro, Thaila Fernanda dos Reis, Stephen K. Dolan, Adriana Oliveira Manfiolli, Neil Andrew Brown, Gary W. Jones, Sean Doyle, Diego M. Riaño-Pachón, Fábio Márcio Squina, Camila Caldana, Ashutosh Singh, Maurizio Del Poeta, Daisuke Hagiwara, Rafael Silva-Rocha and Gustavo H. Goldman

      Version of Record online: 7 OCT 2016 | DOI: 10.1111/mmi.13484

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      Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. We characterized the A. fumigatus Sch9 homologue (SchA) showing that SchA is important for integrating calcium signalling, sphingolipid biosynthesis, hyperosmotic stress, and was involved in iron metabolism. The ΔschA was avirulent in a low dose murine infection model. SchA represents an important protein kinase at the interface between osmotic stress, iron sensing, sphingolipid biosynthesis, calcium metabolism, and pathogenicity in this important opportunistic human pathogen.

    3. You have full text access to this OnlineOpen article
      Off-pathway assembly of fimbria subunits is prevented by chaperone CfaA of CFA/I fimbriae from enterotoxigenic E. coli

      Rui Bao, Yang Liu, Stephen J. Savarino and Di Xia

      Version of Record online: 7 OCT 2016 | DOI: 10.1111/mmi.13530

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      The colonization factor antigen I (CFA/I) pili are archetypal of a group of human-specific enterotoxigenic E. coli (ETEC) and are assembled via the alternate chaperone-usher pathway. Here, we present the structure of the chaperone CfaA in complex with subunit CfaB and demonstrate that the role of CfaA in CFA/I pilus assembly is to avoid off pathway self-polymerization of the subunit CfaB (dotted arrows).

    4. The bacteriophage-derived transcriptional regulator, LscR, activates the expression of levansucrase genes in Pseudomonas syringae

      Khaled Abdallah, Katharina Hartman, Daniel Pletzer, Daria Zhurina and Matthias S. Ullrich

      Version of Record online: 7 OCT 2016 | DOI: 10.1111/mmi.13536

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      Bacterial blight pathogen of soybean, Pseudomonas syringae pv. glycinea PG4180, produces the exopolymer levan under sucrose-rich conditions using the enzyme levansucrase. By functional screening of the PG4180 genome for regulators of levansucrase expression, a prophage-borne transcriptional activator termed LscR was identified and shown to physically interact with the upstream region of levansucrase genes. A lscR-deficient mutant of PG4180 showed a clear levan-negative phenotype (right) compared to the wildtype (left) when grown on sucrose-rich agar medium.

    5. Candida albicans responds to glycostructure damage by Ace2-mediated feedback regulation of Cek1 signaling

      Lasse van Wijlick, Marc Swidergall, Philipp Brandt and Joachim F. Ernst

      Version of Record online: 7 OCT 2016 | DOI: 10.1111/mmi.13494

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      Defective glycosyl structures are sensed by the Msb2 cell wall protein, which transmits its signal to the Cek1 MAPK, which in turn activates the Ace2 transcription factor. Ace2 then upregulates expression of PMT genes encoding mannosyltransferases and amplifies the pathway further by transcriptional upregulation of upstream components. The activity of the pathway is downregulated eventually by the Cst20 MAPKKK (green staining), which enters the nucleus (red staining) and inhibits Ace2 activitiy.

    6. Thiol-based switch mechanism of virulence regulator AphB modulates oxidative stress response in vibrio cholerae

      Zhi Liu, Hui Wang, Zhigang Zhou, Ying Sheng, Nawar Naseer, Biao Kan and Jun Zhu

      Version of Record online: 4 OCT 2016 | DOI: 10.1111/mmi.13524

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      Like many other bacteria, the human pathogen Vibrio cholerae is able to combat reactive oxygen species (ROS). We found that V. cholerae virulence regulator AphB works together with organic hydroperoxide resistance regulator OhrR to regulate ROS resistance through OhrA. AphB and OhrR respond to redox potentials differently so that they fine-tune ohrA expression to better adapt various environmental niches.

    7. Redox pathway sensing bile salts activates virulence gene expression in Vibrio cholerae

      Yuanyuan Xue, Fei Tu, Mengting Shi, Chun-qin Wu, Guoping Ren, Xiaojie Wang, Weihuan Fang, Houhui Song and Menghua Yang

      Version of Record online: 4 OCT 2016 | DOI: 10.1111/mmi.13497

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      In the absence of taurocholate (TC), DsbA will quickly oxidize TcpP to form inhibitory intramolecular disulphide bond (A). In the presence of TC, TC binds to DsbA and inhibits its reductase activities. VcDsbA will be only partially in the oxidized form, thus newly synthesized TcpP will escape from VcDsbA oxidation to form intermolecular disulphide bonds, which helps to maintain the dimerized state of TcpP as functional transcriptional regulator (B).

    8. Single-molecule dynamics of the molecular chaperone trigger factor in living cells

      Feng Yang, Tai-Yen Chen, Łukasz Krzemiński, Ace George Santiago, Won Jung and Peng Chen

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/mmi.13529

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      In bacteria, trigger factor (TF) is the molecular chaperone that interacts with the ribosome to assist the folding of nascent polypeptides. We use single-molecule tracking, photoconvertible bimolecular fluorescence complementation and genetic manipulations to probe the function and dynamics of TF and TF2 dimers in live E. coli cells. We gain insights into how TF and TF2 interact with the ribosome, the polypeptides, the DnaK/DnaJ chaperones, or the signal recognition particle in living cells.

  4. MicroReview

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      Atypical modes of bacterial histidine kinase signaling

      Jonathan W. Willett and Sean Crosson

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/mmi.13525

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      Recent studies have defined atypical modes of bacterial histidine kinase interactions, which enable complex signal integration. We highlight some of these unusual examples and discuss their significance within this MicroReview.

  5. MicroCommentary

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      The modular nature of the β-barrel assembly machinery, illustrated in Borrelia burgdorferi

      Christopher Stubenrauch, Rhys Grinter and Trevor Lithgow

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/mmi.13527

  6. Research Articles

    1. The SAGA complex in the rice pathogen Fusarium fujikuroi: structure and functional characterization

      Sarah M. Rösler, Katharina Kramer, Iris Finkemeier, Hans-Ulrich Humpf and Bettina Tudzynski

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/mmi.13528

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      The Spt-Ada-Gcn5 acetyltransferase complex is highly conserved in the rice pathogen Fusarium fujikuroi, except for the missing DUBm module and Chd1 known from Saccharomyces cerevisiae. We show that Gcn5 is essential for the acetylation of several lysine residues of histone 3, the formation of conidia and wild type-like growth in F. fujikuroi. A genome-wide microarray analysis revealed differential expression of genes mainly involved in secondary metabolism, transport and gene regulation by GCN5 deletion.

    2. Thf1 interacts with PS I and stabilizes the PS I complex in Synechococcus sp. PCC7942

      Jiao Zhan, Xi Zhu, Wei Zhou, Hui Chen, Chenliu He and Qiang Wang

      Version of Record online: 27 SEP 2016 | DOI: 10.1111/mmi.13488

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      Using the model cyanobacterium Synechococcus sp. PCC7942, we showed that the thylakoid membrane system was not affected in the thf1 deletion strain. Defect of Thf1 increases the high light sensitivity, PS I was found more seriously affected than PS II in ΔThf1 and further analysis indicated that Thf1 interacts with PS I and thereby stabilizes PS I.

    3. The role of two branched-chain amino acid transporters in Staphylococcus aureus growth, membrane fatty acid composition and virulence

      Julienne C. Kaiser, Suranjana Sen, Anshul Sinha, Brian J. Wilkinson and David E. Heinrichs

      Version of Record online: 27 SEP 2016 | DOI: 10.1111/mmi.13495

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      The branched-chain amino acids (BCAAs; Ile, Leu, Val) are important nutrients for Staphylococcus aureus physiology and virulence, and yet it does not readily synthesize Leu and Val. Here, we show that S. aureus acquires free BCAAs via the transporters BrnQ1 and BcaP. Although BrnQ1 plays a predominant role in supplying Leu and Val for growth and synthesis of branched-chain fatty acids in vitro, both BrnQ1 and BcaP are required for optimal fitness of S. aureus in vivo.

    4. McmA-dependent and -independent regulatory systems governing expression of ClrB-regulated cellulase and hemicellulase genes in Aspergillus nidulans

      Nuo Li, Emi Kunitake, Miki Aoyama, Masahiro Ogawa, Kyoko Kanamaru, Makoto Kimura, Yasuji Koyama and Tetsuo Kobayashi

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/mmi.13493

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      ClrB and McmA in Aspergillus nidulans regulate cellulase and hemicellulase genes in Aspergillus nidulans, however, McmA dependency of ClrB-target genes are gene-dependent. McmA assists in the recruitment of a ClrB monomer to the cellulose-responsive element (CeRE) in the promoters of eglA and eglB, while ClrB does not require McmA for binding as a dimer to the CGGN8CCG sequences in the mndB promoter. Thus, there are two types of ClrB-mediated regulation: McmA-assisted and McmA-independent.

    5. Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of Burkholderia pseudomallei

      Rafael Custódio, Christopher J. McLean, Andrew E. Scott, Jonathan Lowther, Amanda Kennedy, David J. Clarke, Dominic J. Campopiano, Mitali Sarkar-Tyson and Alan R. Brown

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/mmi.13531

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      Following phagocytosis, sphingosine-1-phosphate (S1P) lyases are secreted by Burkholderia pseudomallei (1). These S1P lyases catalyse the irreversible degradation of S1P, a bioactive sphingolipid metabolite that promotes phagosome maturation (2). These bacterial S1P lyases promote escape from endocytic vacuoles and subsequent intracellular replication (3). S1P lyase-deficient Burkholderia are unable to evade the maturing phagosome and display attenuated virulence. Treatment of infected macrophages with exogenous S1P circumvents the activity of the bacterial S1P lyases, enhancing bacterial killing.

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      High resolution microscopy reveals an unusual architecture of the Plasmodium berghei endoplasmic reticulum

      Gesine Kaiser, Mariana De Niz, Benoît Zuber, Paul-Christian Burda, Benoît Kornmann, Volker T. Heussler and Rebecca R. Stanway

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/mmi.13490

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      During asexual replication, Plasmodium berghei parasites generate huge accumulations of the endoplasmic reticulum (ER), which disappear upon formation of single daughter parasites. Analysing the ER of liver stage parasites using high-resolution microscopy, we defined ER accumulations as intricate dense networks of ribosome-free ER tubules. Plasmodium parasites possess a vastly reduced unfolded protein response machinery and we hypothesize that ER accumulations serve as an alternative mechanism to alleviate ER stress.

  7. Research Article

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      Transcription factor PRO1 targets genes encoding conserved components of fungal developmental signaling pathways

      Eva Katharina Steffens, Kordula Becker, Sabine Krevet, Ines Teichert and Ulrich Kück

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/mmi.13491

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      PRO 1 is a Zn(II)2Cys6 zinc binuclear cluster transcription factor that controls fruiting body development in the sexual life cycle of the filamentous fungus Sordaria macrospora. ChIP-seq analysis showed that PRO1 binds to promoter regions of developmental genes encoding components of conserved signaling complexes.

  8. Research Articles

    1. Lytic transglycosylases LtgA and LtgD perform distinct roles in remodeling, recycling and releasing peptidoglycan in Neisseria gonorrhoeae

      Ryan E. Schaub, Yolande A. Chan, Mijoon Lee, Dusan Hesek, Shahriar Mobashery and Joseph P. Dillard

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/mmi.13496

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      Neisseria gonorrhoeae releases a significant portion of cell wall-derived peptidoglycan fragments, inducing inflammation and tissue damage in the genital tract. This work describes the functions of the two lytic transglycosylases responsible for producing the peptidoglycan fragments tracheal cytotoxin and GlcNAc-anhydro-MurNAc-tripeptide, a Nod1 agonist. Although these two enzymes can perform the same biochemical reaction, each lytic transglycosylase has different substrate specificity and cellular localization that leads to differing contributions to peptidoglycan remodeling, recycling, and release.

    2. Differentially regulated high-affinity iron assimilation systems support growth of the various cell types in the dimorphic pathogen Talaromyces marneffei

      Shivani Pasricha, Lukas Schafferer, Herbert Lindner, Kylie Joanne Boyce, Hubertus Haas and Alex Andrianopoulos

      Version of Record online: 23 SEP 2016 | DOI: 10.1111/mmi.13489

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      The opportunistic fungal pathogen Talaromyces marneffei (formerly known as Penicillium marneffei) is endemic to Southeast Asia and represents an important and escalating health threat to immunocompromised individuals. T. marneffei undergoes a thermally dependent morphological switch from non-pathogenic hyphal cells at 25°C to pathogenic yeast cells at 37°C. The ability of pathogenic fungi to proliferate within the host is dictated by strategic acquisition of nutrients, such as iron. Two iron-uptake mechanisms have been identified in fungi for the acquisition of iron under low iron conditions, these include the reductive and non-reductive iron assimilation systems. Restricting the ability of fungi to acquire iron through these systems has been shown to reduce virulence and is a possible avenue for disease control. In this study, we show that T. marneffei yeast cells rely on both iron uptake systems, highlighting a key difference between hyphal and yeast cell types, and this may be an explanation for their success within host cells as they may scavenge iron more effectively. In addition we identified the presence of a duplicated non-reductive iron assimilation gene, relatively uncommon amongst other fungi. Deletion of this gene resulted in severe growth defects under low iron conditions and presents itself as a good target for antifungal drugs.

    3. SuperSegger: robust image segmentation, analysis and lineage tracking of bacterial cells

      Stella Stylianidou, Connor Brennan, Silas B. Nissen, Nathan J. Kuwada and Paul A. Wiggins

      Version of Record online: 23 SEP 2016 | DOI: 10.1111/mmi.13486

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      SuperSegger is an automated cell image segmentation, tracking and analysis package that facilitates robust, rapid and quantitative analysis of bacterial cell biology. The package is particularly well suited to time-lapse imaging over multiple generations. We demonstrate the power of this package by analyzing bacterial proliferation in lag-phase growth with single cell resolution.

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      The TamB ortholog of Borrelia burgdorferi interacts with the β-barrel assembly machine (BAM) complex protein BamA

      Henna Iqbal, Melisha R. Kenedy, Meghan Lybecker and Darrin R. Akins

      Version of Record online: 23 SEP 2016 | DOI: 10.1111/mmi.13492

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      Borrelia burgdorferi encodes a TamB-like protein. TamB proteins from Proteobacteria interact with TamA to form the translocation and assemble module (TAM). Spirochetes and many other organisms, however, do not contain a TamA protein, although they encode TamB homologs. Here, we show that the TamB homolog from B. burgdorferi interacts with the BamA protein of the β-barrel assembly machine (BAM) and suggest this may be a common interaction in organisms that lack TamA and a TAM.

    5. You have full text access to this OnlineOpen article
      Functional characterization of a gene locus from an uncultured gut Bacteroides conferring xylo-oligosaccharides utilization to Escherichia coli

      Alexandra S. Tauzin, Elisabeth Laville, Yao Xiao, Sébastien Nouaille, Pascal Le Bourgeois, Stéphanie Heux, Jean-Charles Portais, Pierre Monsan, Eric C. Martens, Gabrielle Potocki-Veronese and Florence Bordes

      Version of Record online: 14 SEP 2016 | DOI: 10.1111/mmi.13480

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      A Polysaccaride Utilization Locus from Bacteroides vulgatus previously evidenced by functional metagenomic confers to E. coli the ability to grow on xylo-oligosaccharides thanks to glycoside hydrolases and two transport systems.

    6. You have full text access to this OnlineOpen article
      UAP56 is a conserved crucial component of a divergent mRNA export pathway in Toxoplasma gondii

      Mariana Serpeloni, Elena Jiménez-Ruiz, Newton Medeiros Vidal, Constanze Kroeber, Nicole Andenmatten, Leandro Lemgruber, Patricia Mörking, Gurman S. Pall, Markus Meissner and Andréa R. Ávila

      Version of Record online: 14 SEP 2016 | DOI: 10.1111/mmi.13485

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      mRNA export is well characterized in mammals but poorly understood in single-cell parasites and other divergent organisms. We have utilized sequence searching, phylogenetic analyses and reverse genetic tools to investigate this pathway in Toxoplasma gondii, a parasite that causes Toxoplasmosis in humans and is related to the malaria causing parasite. This study has revealed essential factors and point towards that this parasite may have undiscovered unique components for mRNA export.

    7. Structural basis for Myf and Psa fimbriae-mediated tropism of pathogenic strains of Yersinia for host tissues

      Natalia Pakharukova, Saumendra Roy, Minna Tuittila, Mohammad M. Rahman, Sari Paavilainen, Anna-Karin Ingars, Maksym Skaldin, Urpo Lamminmäki, Torleif Härd, Susann Teneberg and Anton V. Zavialov

      Version of Record online: 14 SEP 2016 | DOI: 10.1111/mmi.13481

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      Pathogenic Yersiniae assemble two homologous fimbrial adhesins, Myf and Psa. We discovered Myf-specific receptors and determined the structural basis for receptor recognition by Myf and Psa. These results suggest that both adhesins play an important role in the tissue tropism of Yersiniae, but mediate attachment to different tissues and facilitate different routes of Yersiniae transmission. The structures reveal the mechanism underlying the evolution of the adhesive properties of these pathogens.

    8. Minimal cytosolic iron-sulfur cluster assembly machinery of Giardia intestinalis is partially associated with mitosomes

      Jan Pyrih, Eva Pyrihová, Martin Kolísko, Darja Stojanovová, Somsuvro Basu, Karel Harant, Alexander C. Haindrich, Pavel Doležal, Julius Lukeš, Andrew Roger and Jan Tachezy

      Version of Record online: 6 SEP 2016 | DOI: 10.1111/mmi.13487

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      Minimal cytosolic iron-sulfur cluster assembly (CIA) pathway of Giardia intestinalis comprises of Nbp35, Nar1, Cia1, and Cia2 proteins whereas essential electron donor Tah18/Dre2 complex, as well as Cfd1 and MMS19 seems to be absent in this parasite. In addition to the cytosolic localization, Cia2 and Nbp35 are associated with mitosomes and might represent a novel connection between the mitosomal FeS cluster assembly (ISC) and the CIA pathway.

    9. MAB_3551c encodes the primary triacylglycerol synthase involved in lipid accumulation in Mycobacterium abscessus

      Albertus Viljoen, Mickael Blaise, Chantal de Chastellier and Laurent Kremer

      Version of Record online: 4 SEP 2016 | DOI: 10.1111/mmi.13482

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      In the triacylglycerol (TAG)-rich environment of very low density lipoprotein (VLDL)-induced foamy macrophages, Mycobacterium abscessus uses MAB_3551c to produce TAG. This TAG accumulates in the form of ILI, representing a rich source of energy and carbon.

    10. The roles of AtxA orthologs in virulence of anthrax-like Bacillus cereus G9241

      Jennifer M. Scarff, Malik J. Raynor, Yuliya I. Seldina, Christy L. Ventura, Theresa M. Koehler and Alison D. O'Brien

      Version of Record online: 4 SEP 2016 | DOI: 10.1111/mmi.13478

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      AtxA is the predominant regulator of toxin and capsule production in Bacillus anthracis. Here, we characterized two AtxA orthologs, AtxA1 and AtxA2, in the anthrax-like Bacillus cereus strain G9241. We demonstrated that AtxA1 and AtxA2 have the capacity to regulate the production of the anthrax toxins and two unique capsules in G9241 and that deletion of these genes alone or in combination altered the virulence of spores in mice.

    11. A role for copper in protozoan grazing – two billion years selecting for bacterial copper resistance

      Xiuli Hao, Freja Lüthje, Regin Rønn, Nadezhda A. German, Xuanji Li, Fuyi Huang, Javan Kisaka, David Huffman, Hend A. Alwathnani, Yong-Guan Zhu and Christopher Rensing

      Version of Record online: 31 AUG 2016 | DOI: 10.1111/mmi.13483

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      Protozoans are ubiquitous bacterial predators and pathogen reservoirs. We have characterized the protozoan use of copper as an efficient weapon during predation. Thus copper poisoning imposes a selective pressure upon copper resistance determinants in bacteria.

    12. Cell cycle regulation and novel structural features of thymidine kinase, an essential enzyme in Trypanosoma brucei

      Maria Valente, Jennifer Timm, Víctor M. Castillo-Acosta, Luis M. Ruiz-Pérez, Tom Balzarini, Joanne E. Nettleship, Louise E Bird, Heather Rada, Keith S. Wilson and Dolores González-Pacanowska

      Version of Record online: 31 AUG 2016 | DOI: 10.1111/mmi.13467

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      In this study, we establish that the depletion of Trypanosoma brucei thymidine kinase (TbTK) leads to strongly diminished dTTP pools, DNA damage and parasite death. We show that TbTK expression is cell cycle regulated and essential for cell cycle progression. In addition, we report the X-ray structure of the catalytically active domain of TbTK and identify structural peculiarities within the active site that could be exploited in the process of rational drug design.

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. 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.

    20. 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.

    21. 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.

    22. 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.

    23. 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.


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