Volume 561 Issue 7722, 13 September 2018

Volume 561 Issue 7722

Seconds out

The rise of multidrug-resistant bacteria is cause for considerable concern and the ‘ESKAPE’ group of pathogens present the most acute risk of untreatable infections. The Gram-negative bacteria within this group — iEscherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii — are of particular concern because their dual-membrane envelope stops many drugs from reaching their targets. Despite extensive efforts, no new antibiotic active against Gram-negative bacteria has been approved in the past 50 years. In this week’s issue, Christopher Heise, Peter Smith and their colleagues present the chemical optimization of the arylomycin class of natural products into a potent, broad-spectrum drug that is active against clinical isolates of Gram-negative bacteria in vitro and in multiple in vivo infection models. The team believes this should pave the way for optimized arylomycin analogues to become much-needed new drugs for multidrug-resistant Gram-negative infections.

Cover image: Marina Muun

This Week

News in Focus

Comment

Technology

Careers

Futures

  • Futures |

    A taste of success.

    • Dave Kavanaugh

Research

    News & Views

  • News & Views |

    The protein RANKL is released by bone-forming cells called osteoblasts, and binds to its receptor, RANK, on osteoclast cells to trigger bone removal. It emerges that the pathway can act in reverse to stimulate bone formation.

    • Mone Zaidi
    •  & Christopher P. Cardozo
  • News & Views |

    Controlled long-distance transport of electron spins is required for a kind of electronics known as spintronics. Such transport has been realized in an antiferromagnet, the most common type of magnetic material.

    • Sergio M. Rezende
  • News & Views |

    Sheets of cells called epithelia can curve into tubes in embryos. Modelling and in vivo observations reveal that cells in tubes adopt an asymmetric cell shape dubbed scutoid, contrary to some previous assumptions.

    • Guy Blanchard
  • News & Views |

    Computational simulations suggest that future losses of tidal wetlands attributable to sea-level rise could be greatly offset by the landward advance of these ecosystems into newly sea-inundated areas.

    • Jonathan D. Woodruff
  • News & Views |

    PINK1 and parkin proteins help to degrade damaged mitochondrial organelles, and abnormalities in these proteins are linked to Parkinson’s disease. Mouse studies reveal that the proteins act to prevent inflammation.

    • Alexandra Stolz
    •  & Ivan Dikic
  • News & Views |

    An investigation finds that most protein complexes in yeast cells assemble before the subunits have fully formed. This mechanism might prevent the formation of toxic protein aggregates.

    • Christine Mayr
  • Brief Communications Arising

  • Articles

  • Article |

    Chemical optimization of arylomycins results in an inhibitor of bacterial type I signal peptidase that shows activity both against multidrug-resistant clinical isolates of Gram-negative bacteria in vitro and in several in vivo infection models.

    • Peter A. Smith
    • , Michael F. T. Koehler
    • , Hany S. Girgis
    • , Donghong Yan
    • , Yongsheng Chen
    • , Yuan Chen
    • , James J. Crawford
    • , Matthew R. Durk
    • , Robert I. Higuchi
    • , Jing Kang
    • , Jeremy Murray
    • , Prasuna Paraselli
    • , Summer Park
    • , Wilson Phung
    • , John G. Quinn
    • , Tucker C. Roberts
    • , Lionel Rougé
    • , Jacob B. Schwarz
    • , Elizabeth Skippington
    • , John Wai
    • , Min Xu
    • , Zhiyong Yu
    • , Hua Zhang
    • , Man-Wah Tan
    •  & Christopher E. Heise
  • Article |

    Osteoclasts secrete small extracellular vesicles that stimulate osteoblasts, promoting bone formation via receptor activator of nuclear factor-kappa B ligand (RANKL), thereby linking bone formation and resorption.

    • Yuki Ikebuchi
    • , Shigeki Aoki
    • , Masashi Honma
    • , Madoka Hayashi
    • , Yasutaka Sugamori
    • , Masud Khan
    • , Yoshiaki Kariya
    • , Genki Kato
    • , Yasuhiko Tabata
    • , Josef M. Penninger
    • , Nobuyuki Udagawa
    • , Kazuhiro Aoki
    •  & Hiroshi Suzuki
  • Article |

    Comparison of multiple lesions from individual pancreases sheds light on how ancestral clones can spread through the ductal system and give rise to precursor lesions, with acquisition of further mutations leading to pancreatic cancer.

    • Alvin P. Makohon-Moore
    • , Karen Matsukuma
    • , Ming Zhang
    • , Johannes G. Reiter
    • , Jeffrey M. Gerold
    • , Yuchen Jiao
    • , Lisa Sikkema
    • , Marc A. Attiyeh
    • , Shinichi Yachida
    • , Corinne Sandone
    • , Ralph H. Hruban
    • , David S. Klimstra
    • , Nickolas Papadopoulos
    • , Martin A. Nowak
    • , Kenneth W. Kinzler
    • , Bert Vogelstein
    •  & Christine A. Iacobuzio-Donahue
  • Letters

  • Letter |

    Observations of a hot flow anomaly accelerating solar-wind ions suggest a mechanism for such acceleration—a Fermi acceleration trap caused by Earth’s bow shock interacting with the solar wind.

    • D. L. Turner
    • , L. B. Wilson III
    • , T. Z. Liu
    • , I. J. Cohen
    • , S. J. Schwartz
    • , A. Osmane
    • , J. F. Fennell
    • , J. H. Clemmons
    • , J. B. Blake
    • , J. Westlake
    • , B. H. Mauk
    • , A. N. Jaynes
    • , T. Leonard
    • , D. N. Baker
    • , R. J. Strangeway
    • , C. T. Russell
    • , D. J. Gershman
    • , L. Avanov
    • , B. L. Giles
    • , R. B. Torbert
    • , J. Broll
    • , R. G. Gomez
    • , S. A. Fuselier
    •  & J. L. Burch
  • Letter | | open

    The observation of the 1S–2P Lyman-α transition in the antihydrogen atom, the antimatter counterpart of hydrogen, is reported.

    • M. Ahmadi
    • , B. X. R. Alves
    • , C. J. Baker
    • , W. Bertsche
    • , A. Capra
    • , C. Carruth
    • , C. L. Cesar
    • , M. Charlton
    • , S. Cohen
    • , R. Collister
    • , S. Eriksson
    • , A. Evans
    • , N. Evetts
    • , J. Fajans
    • , T. Friesen
    • , M. C. Fujiwara
    • , D. R. Gill
    • , J. S. Hangst
    • , W. N. Hardy
    • , M. E. Hayden
    • , E. D. Hunter
    • , C. A. Isaac
    • , M. A. Johnson
    • , J. M. Jones
    • , S. A. Jones
    • , S. Jonsell
    • , A. Khramov
    • , P. Knapp
    • , L. Kurchaninov
    • , N. Madsen
    • , D. Maxwell
    • , J. T. K. McKenna
    • , S. Menary
    • , J. M. Michan
    • , T. Momose
    • , J. J. Munich
    • , K. Olchanski
    • , A. Olin
    • , P. Pusa
    • , C. Ø. Rasmussen
    • , F. Robicheaux
    • , R. L. Sacramento
    • , M. Sameed
    • , E. Sarid
    • , D. M. Silveira
    • , D. M. Starko
    • , G. Stutter
    • , C. So
    • , T. D. Tharp
    • , R. I. Thompson
    • , D. P. van der Werf
    •  & J. S. Wurtele
  • Letter |

    Rates of radiative heat transfer between sub-wavelength planar membranes are experimentally and theoretically shown to exceed the blackbody limit in the far field by more than two orders of magnitude.

    • Dakotah Thompson
    • , Linxiao Zhu
    • , Rohith Mittapally
    • , Seid Sadat
    • , Zhen Xing
    • , Patrick McArdle
    • , M. Mumtaz Qazilbash
    • , Pramod Reddy
    •  & Edgar Meyhofer
  • Letter |

    Tunable spin transport over long distances is demonstrated through the antiferromagnetic insulator haematite, paving the way to the development of spin-logic devices based on antiferromagnetic insulators.

    • R. Lebrun
    • , A. Ross
    • , S. A. Bender
    • , A. Qaiumzadeh
    • , L. Baldrati
    • , J. Cramer
    • , A. Brataas
    • , R. A. Duine
    •  & M. Kläui
  • Letter |

    A global modelling approach shows that in response to rises in global sea level, gains of up to 60% in coastal wetland areas are possible, if appropriate coastal management solutions are developed to help support wetland resilience.

    • Mark Schuerch
    • , Tom Spencer
    • , Stijn Temmerman
    • , Matthew L. Kirwan
    • , Claudia Wolff
    • , Daniel Lincke
    • , Chris J. McOwen
    • , Mark D. Pickering
    • , Ruth Reef
    • , Athanasios T. Vafeidis
    • , Jochen Hinkel
    • , Robert J. Nicholls
    •  & Sally Brown
  • Letter |

    Meristems of the rooting axes of Asteroxylon mackiei preserved in 407-million-year-old Rhynie chert lack root caps, which demonstrates that the evolution of the root systems of modern vascular plants occurred in a stepwise fashion.

    • Alexander J. Hetherington
    •  & Liam Dolan
  • Letter |

    Four transcription factors that specify keratinocyte cell fate, facilitate in vivo reprogramming of wound-resident mesenchymal cells, epithealization and regeneration of skin epithelial tissues in mice.

    • Masakazu Kurita
    • , Toshikazu Araoka
    • , Tomoaki Hishida
    • , David D. O’Keefe
    • , Yuta Takahashi
    • , Akihisa Sakamoto
    • , Masahiro Sakurai
    • , Keiichiro Suzuki
    • , Jun Wu
    • , Mako Yamamoto
    • , Reyna Hernandez-Benitez
    • , Alejandro Ocampo
    • , Pradeep Reddy
    • , Maxim Nikolaievich Shokhirev
    • , Pierre Magistretti
    • , Estrella Núñez Delicado
    • , Hitomi Eto
    • , Kiyonori Harii
    •  & Juan Carlos Izpisua Belmonte
  • Letter |

    The plant receptor kinase co-receptor BAK1 contains phosphosites that are required for immune function but not for brassinosteroid-regulated growth in Arabidopsis thaliana; an additional tyrosine phosphosite may be required for the function of many Arabidopsis receptor kinases.

    • Artemis Perraki
    • , Thomas A. DeFalco
    • , Paul Derbyshire
    • , Julian Avila
    • , David Séré
    • , Jan Sklenar
    • , Xingyun Qi
    • , Lena Stransfeld
    • , Benjamin Schwessinger
    • , Yasuhiro Kadota
    • , Alberto P. Macho
    • , Shushu Jiang
    • , Daniel Couto
    • , Keiko U. Torii
    • , Frank L. H. Menke
    •  & Cyril Zipfel
  • Letter |

    Integrative analyses identify host proteins that are modulated by Zika virus at multiple levels and provide a comprehensive framework for the understanding of Zika virus-induced changes to cellular pathways.

    • Pietro Scaturro
    • , Alexey Stukalov
    • , Darya A. Haas
    • , Mirko Cortese
    • , Kalina Draganova
    • , Anna Płaszczyca
    • , Ralf Bartenschlager
    • , Magdalena Götz
    •  & Andreas Pichlmair
  • Letter |

    Acute and chronic mitochondrial stress in mice require PINK1 and parkin to restrain STING-mediated innate immunity.

    • Danielle A. Sliter
    • , Jennifer Martinez
    • , Ling Hao
    • , Xi Chen
    • , Nuo Sun
    • , Tara D. Fischer
    • , Jonathon L. Burman
    • , Yan Li
    • , Zhe Zhang
    • , Derek P. Narendra
    • , Huaibin Cai
    • , Max Borsche
    • , Christine Klein
    •  & Richard J. Youle
  • Letter |

    During starvation, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) targets GTPase-activating proteins to inhibit multiple intracellular transport pathways, thereby promoting energy homeostasis.

    • Jia-Shu Yang
    • , Jia-Wei Hsu
    • , Seung-Yeol Park
    • , Jian Li
    • , William M. Oldham
    • , Galina V. Beznoussenko
    • , Alexander A. Mironov
    • , Joseph Loscalzo
    •  & Victor W. Hsu
  • Letter |

    Cotranslational assembly is a prevalent mechanism for the formation of oligomeric complexes in Saccharomyces cerevisiae, with one subunit serving as scaffold for the translation of partner subunits.

    • Ayala Shiber
    • , Kristina Döring
    • , Ulrike Friedrich
    • , Kevin Klann
    • , Dorina Merker
    • , Mostafa Zedan
    • , Frank Tippmann
    • , Günter Kramer
    •  & Bernd Bukau

Amendments & Corrections

  • Author Correction |

    • Emmanuelle Szenker-Ravi
    • , Umut Altunoglu
    • , Marc Leushacke
    • , Célia Bosso-Lefèvre
    • , Muznah Khatoo
    • , Hong Thi Tran
    • , Thomas Naert
    • , Rivka Noelanders
    • , Amin Hajamohideen
    • , Claire Beneteau
    • , Sergio B. de Sousa
    • , Birsen Karaman
    • , Xenia Latypova
    • , Seher Başaran
    • , Esra Börklü Yücel
    • , Thong Teck Tan
    • , Lena Vlaminck
    • , Shalini S. Nayak
    • , Anju Shukla
    • , Katta Mohan Girisha
    • , Cédric Le Caignec
    • , Natalia Soshnikova
    • , Zehra Oya Uyguner
    • , Kris Vleminckx
    • , Nick Barker
    • , Hülya Kayserili
    •  & Bruno Reversade
  • Publisher Correction |

    • Elwira Smakowska-Luzan
    • , G. Adam Mott
    • , Katarzyna Parys
    • , Martin Stegmann
    • , Timothy C Howton
    • , Mehdi Layeghifard
    • , Jana Neuhold
    • , Anita Lehner
    • , Jixiang Kong
    • , Karin Grünwald
    • , Natascha Weinberger
    • , Santosh B. Satbhai
    • , Dominik Mayer
    • , Wolfgang Busch
    • , Mathias Madalinski
    • , Peggy Stolt-Bergner
    • , Nicholas J. Provart
    • , M. Shahid Mukhtar
    • , Cyril Zipfel
    • , Darrell Desveaux
    • , David S. Guttman
    •  & Youssef Belkhadir

Spotlight

  • Spotlight |

    Earth observation

    Earth-observation scientists are powering through an uncertain funding landscape to understand a changing climate better.