Antibacterial drug resistance articles within Nature Communications

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  • Article
    | Open Access

    Inhibition of bacterial cell wall synthesis by β-lactam antibiotics results in a loss of cell wall integrity, but cells die via a combination of downstream events involving metabolic perturbations and oxidative damage. Here, Kawai et al. identify key enzymatic steps that stimulate the generation of reactive oxygen species and highlight the role of iron homeostasis in the lethal effects mediated by oxidative damage.

    • Yoshikazu Kawai
    • , Maki Kawai
    •  & Jeff Errington

  • Article
    | Open Access

    Deep mutational scanning can be used to investigate protein function and stability. Here, Dewachter et al. use deep mutational scanning on three essential bacterial proteins to study the mutations’ effects in their original genomic context, providing insight into the proteins’ function and their potential as targets for new antibiotic development.

    • Liselot Dewachter
    • , Aaron N. Brooks
    •  & Jan Michiels

  • Article
    | Open Access

    Antibiotic persisters are phenotypic variants within an isogenic bacterial population that are transiently tolerant to antibiotic treatment. Here, the authors provide evidence that cytoplasmic acidification, amplified by a compromised respiratory complex I, can act as a signaling hub for perturbed metabolic homeostasis in antibiotic persisters.

    • Bram Van den Bergh
    • , Hannah Schramke
    •  & Matthias Heinemann

  • Article
    | Open Access

    Bacterial transcriptomic data have been used to predict antibiotic susceptibility in a species- or antibiotic-specific manner. Here, the authors show that global transcriptional disorder is a common stress response in bacteria with low fitness, and present a general approach that can predict bacterial fitness independently of species or type of stress.

    • Zeyu Zhu
    • , Defne Surujon
    •  & Tim van Opijnen

  • Article
    | Open Access

    Bacterial persister cells exhibit a transient non-growing state and antibiotic tolerance. Here, Peyrusson et al. provide evidence of metabolically active Staphylococcus aureus persisters within infected host cells exposed to antibiotics and analyse transcriptomic alterations associated with persistence.

    • Frédéric Peyrusson
    • , Hugo Varet
    •  & Françoise Van Bambeke

  • Article
    | Open Access

    The reservoir for recurrent urinary tract infection in humans is unclear. Here, Mickiewicz et al. detect cell-wall deficient (L-form) E. coli in fresh urine from patients, and show that the isolated bacteria readily switch between walled and L-form states.

    • Katarzyna M. Mickiewicz
    • , Yoshikazu Kawai
    •  & Jeff Errington

  • Article
    | Open Access

    Bacteria can become dormant or form spores when starved for nutrients. Here, Gray et al. describe an alternative strategy, or ‘oligotrophic growth state’, showing that non-sporulating Bacillus subtilis cells can survive deep starvation conditions by adopting an almost coccoid shape and extremely low growth rates.

    • Declan A. Gray
    • , Gaurav Dugar
    •  & Leendert W. Hamoen

  • Article
    | Open Access

    It is unclear whether the transfer of plasmids carrying antibiotic resistance genes can explain their persistence when antibiotics are not present. Here, Lopatkin et al. show that conjugal plasmids, even when costly, are indeed transferred at sufficiently high rates to be maintained in the absence of antibiotics.

    • Allison J. Lopatkin
    • , Hannah R. Meredith
    •  & Lingchong You

  • Article
    | Open Access

    Transcription factors MarR and MarA confer multidrug resistance in enteric bacteria by modulating efflux pump and porin expression. Here, Sharma et al. show that MarA also upregulates genes required for lipid trafficking and DNA repair, thus reducing antibiotic entry and quinolone-induced DNA damage.

    • Prateek Sharma
    • , James R. J. Haycocks
    •  & David C. Grainger

  • Article
    | Open Access

    The mechanisms of action of the antibacterial metalloid tellurite are unclear. Here, the authors show that tellurite induces an accumulation of hydroxyl radical and intermediates of heme biosynthesis inE. coli, and that the heme precursor 5-aminolevulinic acid potentiates tellurite toxicity.

    • Eduardo H. Morales
    • , Camilo A. Pinto
    •  & Claudio C. Vásquez

  • Article
    | Open Access

    The clinical application of new sequencing techniques is expected to accelerate pathogen identification. Here, Bradley et al. present a clinician-friendly software package that uses sequencing data for quick and accurate prediction of antibiotic resistance profiles for S. aureus and M. tuberculosis.

    • Phelim Bradley
    • , N. Claire Gordon
    •  & Zamin Iqbal

  • Article |

    AbgT family of transporters have previously been implicated in the uptake of folate catabolites but remain poorly understood. Here the authors present a structural and functional characterization of Alcanivorax borkumensisYdaH, an AbgT-type transporter, revealing a unique topology and possible function as a drug efflux pump.

    • Jani Reddy Bolla
    • , Chih-Chia Su
    •  & Edward W. Yu

  • Article |

    Overexpression of a drug’s molecular target increases drug resistance in some cases. Here the authors show that overexpressing antibiotic targets in Escherichia colican cause positive and negative changes in drug resistance, depending on whether the drug induces harmful reactions involving its target.

    • Adam C. Palmer
    •  & Roy Kishony

  • Article |

    Mycobacterium tuberculosisis intrinsically resistant to most antibiotics. Here, the authors show that the pathogen’s tolerance to three antibiotics, each one targeting a distinct cellular process, is mediated by an antioxidant response that requires the activation of isocitrate lyases.

    • Madhumitha Nandakumar
    • , Carl Nathan
    •  & Kyu Y. Rhee

  • Article
    | Open Access

    The factors varying mutation rate at a particular site in a single genotype remain elusive. Here, Krašovec et al. show that mutation rates at sites conferring resistance to rifampicin in Escherichia coli decrease with population density, and that mutation-rate plasticity is controlled by the luxSgene.

    • Rok Krašovec
    • , Roman V. Belavkin
    •  & Christopher G. Knight

  • Article |

    New classes of antitubercular drugs are in constant demand as drug-resistant strains of Mycobacterium tuberculosis become more prevalent. Here, the authors characterize a class of drugs that are active against various M. tuberculosisstrains, including those resistant to currently used antituberculars.

    • Shichun Lun
    • , Haidan Guo
    •  & William R. Bishai

  • Article |

    Bacterial persistence is one of the major causes of failure of antibiotic treatment, and several toxin–antitoxin modules have been linked to the persistent phenotype. Here, the authors show that HipA toxin causes growth arrest and persistence via phosphorylation of the glutamyl-tRNA-synthetase.

    • Ilana Kaspy
    • , Eitan Rotem
    •  & Gad Glaser

  • Article
    | Open Access

    RamR is an important multidrug-resistance factor, however, its structure and the molecules to which it responds are hitherto unknown. Here, the authors report the crystal structures of RamR complexed with multiple drugs, revealing significant flexibility in its substrate-recognition region.

    • Suguru Yamasaki
    • , Eiji Nikaido
    •  & Kunihiko Nishino

  • Article |

    Erm methyltransferases confer antimicrobial drug resistance and their expression is induced by macrolides. Gupta et al.show that Erm-catalysed modification of rRNA affects synthesis of some proteins and reduces cell fitness, explaining why expression of Erm is deleterious in the absence of antibiotics.

    • Pulkit Gupta
    • , Shanmugapriya Sothiselvam
    •  & Alexander S. Mankin

  • Article |

    The bacterial tetracycline resistance protein Tet(O) binds to the ribosome, preventing tetracycline from inhibiting translation. Using cryo-electron microscopic reconstruction, the authors present an atomic model of Tet(O) bound to the 70S ribosome, and reveal how Tet(O) promotes antibiotic resistance.

    • Wen Li
    • , Gemma C. Atkinson
    •  & Joachim Frank

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