Volume 8 Issue 1, January 2012

Volume 8 Issue 1

The ability of microorganisms such as bacteria to affect their hosts and cause disease highlights the importance of understanding microbial chemistry and biology and how microbes affect the chemistry and biology of their environment under various conditions, including within communities or when challenged by antimicrobial drugs. With an emphasis on bacteria, this issue features pieces aimed at exploring how microbes interact with their environment and how an understanding of their ecology and evolution can be exploited to generate new antimicrobials. Cover art by Erin Dewalt.


  • Editorial |

    Understanding the molecules and mechanisms that microbes use to interact with each other and their environments can lead to better antimicrobial drug design as well as a richer understanding of bacterial physiology, ecology and evolution.


  • Commentary |

    Antibiotics promote the spread of resistance in the clinic, but various mechanisms may exist in natural environments that tilt the balance toward antibiotic sensitivity. Studying such mechanisms could help us understand the evolutionary dynamics of resistance and sensitivity in the wild, which may inspire new therapeutic strategies.

    • Remy Chait
    • , Kalin Vetsigian
    •  & Roy Kishony
  • Commentary |

    Despite our continued efforts to assert control over pathogens, more and more bacteria are saying “no” to drugs. It is becoming increasingly apparent that microbial environments, influenced by intracellular and extracellular metabolic processes, modulate antibiotic susceptibility in bacteria. A deeper understanding of these environmental processes may prove crucial for the development of new antibacterial therapies.

    • Henry H Lee
    •  & James J Collins
  • Commentary |

    A growing body of evidence points to the importance of microcolonies in the dissemination of bacteria, yet there is a dearth of tools for systematically assessing the behavior of cells within such communities. New strategies for landscaping three-dimensional culture environments on microscopic scales may have a critical role in revealing how bacteria orchestrate antibiotic resistance and other social behaviors within small, dense aggregates.

    • Jodi L Connell
    • , Marvin Whiteley
    •  & Jason B Shear
  • Commentary |

    The distinction between different cell-envelope architectures has defined much of our thinking about bacterial systematics, but the evolution of different envelope layers has been harder to understand. A recent publication focused on the non-model organism Acetonema longum provides important clues to the possible origin of the second membrane typical of Gram-negative bacteria.

    • Waldemar Vollmer

Research Highlights

News and Views

  • News & Views |

    Lysophosphatidic acid, a lipid mediator, second messenger and intermediate in lipid biosynthesis, finds a new intracellular target in TRPV1. This nonselective cation channel is also targeted by the analgesic capsaicin, which acts to desensitize the channel.

    • Gabor Tigyi
  • News & Views |

    Amino acids not only are useful for protein synthesis but also act as regulators of gene expression. An elegant genome-wide approach now shows how binding of amino acids to transcription factors regulates an integrated network of amino acid metabolism to suit the physiological needs of bacterial cells.

    • Tamar Avin-Wittenberg
    •  & Gad Galili
  • News & Views |

    The multisubunit DNA polymerases of eukaryotes have iron-sulfur centers that are crucial for polymerase assembly and therefore the integrity of the nuclear genome.

    • Scott Bailey




  • Article |

    Genome-scale metabolic models provide a map of biochemical reactions in the cell but do not indicate how these reactions are regulated by complex transcriptional networks. Analysis of expression and interaction data now define two distinct roles for amino acids as signaling and nutrient molecules.

    • Byung-Kwan Cho
    • , Stephen Federowicz
    • , Young-Seoub Park
    • , Karsten Zengler
    •  & Bernhard Ø Palsson
  • Article |

    The mass spectrometry and crystallographic characterization of an irreversible O-glycosyltransferase inhibitor surprisingly indicates that the dicarbamate core reacts to form an unusual carbonyl crosslink between two active site residues, probably driven by its ability to serve as a diphosphate mimic.

    • Jiaoyang Jiang
    • , Michael B Lazarus
    • , Lincoln Pasquina
    • , Piotr Sliz
    •  & Suzanne Walker
  • Article |

    Lysophosphatidic acid (LPA), a lipid that induces neuropathic pain, functions by binding directly to the ion channel TRPV1 independently from the G protein–coupled receptors that generally mediate LPA function.

    • Andrés Nieto-Posadas
    • , Giovanni Picazo-Juárez
    • , Itzel Llorente
    • , Andrés Jara-Oseguera
    • , Sara Morales-Lázaro
    • , Diana Escalante-Alcalde
    • , León D Islas
    •  & Tamara Rosenbaum
  • Article |

    Single-molecule studies on a molecular motor F1-ATPase provide evidence that energy from catalysis is gradually converted to mechanical rotation, explaining the high efficiency of energy conversion and the mechanism for positive cooperativity among subunits during ATP hydrolysis.

    • Rikiya Watanabe
    • , Daichi Okuno
    • , Shouichi Sakakihara
    • , Katsuya Shimabukuro
    • , Ryota Iino
    • , Masasuke Yoshida
    •  & Hiroyuki Noji
  • Article |

    An orcein-related small molecule can drive polymerization of amyloid-β, implicated in Alzheimer's disease, without remodeling oligomeric or fibril forms but by stabilizing a seeding-competent protofilament state and shortening the lag phase of spontaneous polymerization.

    • Jan Bieschke
    • , Martin Herbst
    • , Thomas Wiglenda
    • , Ralf P Friedrich
    • , Annett Boeddrich
    • , Franziska Schiele
    • , Daniela Kleckers
    • , Juan Miguel Lopez del Amo
    • , Björn A Grüning
    • , Qinwen Wang
    • , Michael R Schmidt
    • , Rudi Lurz
    • , Roger Anwyl
    • , Sigrid Schnoegl
    • , Marcus Fändrich
    • , Ronald F Frank
    • , Bernd Reif
    • , Stefan Günther
    • , Dominic M Walsh
    •  & Erich E Wanker
  • Article |

    An intramolecular cleft of the FAK FERM domain mediates interaction with sarcomeric myosin. Chemical cross-linking, SAXS and mutational analyses confirm the interaction, and inhibiting the interaction with a peptide activates FAK and promotes the cardiomyocyte hypertrophic response.

    • Aline M Santos
    • , Deborah Schechtman
    • , Alisson C Cardoso
    • , Carolina F M Z Clemente
    • , Júlio C Silva
    • , Mariana Fioramonte
    • , Michelle B M Pereira
    • , Talita M Marin
    • , Paulo S L Oliveira
    • , Ana Carolina M Figueira
    • , Saulo H P Oliveira
    • , Íris L Torriani
    • , Fábio C Gozzo
    • , José Xavier Neto
    •  & Kleber G Franchini
  • Article |

    Enzymes that act on inositol pyrophosphates must accommodate a densely charged substrate while retaining excellent substrate specificity to control downstream signaling networks. Structural and biochemical data now define the basis for substrate recognition and the reaction coordinate for formation of a high-energy pyrophosphate bond.

    • Huanchen Wang
    • , J R Falck
    • , Traci M Tanaka Hall
    •  & Stephen B Shears
  • Article |

    Biochemical and bioinformatic analyses have pointed to crotonyl-CoA carboxylase-reductase homolog as responsible for introducing unusual extender units into polyketide pathways; structural and mutational analysis now defines the basis for this reaction and the mechanism for substrate discrimination.

    • Nick Quade
    • , Liujie Huo
    • , Shwan Rachid
    • , Dirk W Heinz
    •  & Rolf Müller
  • Article |

    DNA polymerases contain two cysteine-rich metal binding motifs (CysA and CysB), which have been assigned as zinc-ion binding sites by structural studies. A combination of biochemical and spectroscopic techniques reveal that the CysB site of yeast B-family polymerases binds a [4Fe-4S] cluster that is essential for polymerase function.

    • Daili J A Netz
    • , Carrie M Stith
    • , Martin Stümpfig
    • , Gabriele Köpf
    • , Daniel Vogel
    • , Heide M Genau
    • , Joseph L Stodola
    • , Roland Lill
    • , Peter M J Burgers
    •  & Antonio J Pierik


  • Focus |


    Small molecules play important roles as metabolites in the physiology, ecology and evolution of microorganisms. This issue includes a collection of articles aimed at understanding the chemical interactions of microbes with their environment, with an aim towards new anti-microbials and new biological insights.