Abstract:
:Overexpression of a drug's molecular target often increases drug resistance, offering a pathway for adaptive evolution and a tool for target identification. It is unclear though why this phenomenon applies to some drugs but not others. Here we gradually overexpressed antibiotic targets in Escherichia coli and found that drug resistance can increase, remain unchanged, decrease or even change non-monotonically. Even a single target can produce opposing responses to its different inhibitors. We explain these contradicting effects with quantitative models of enzyme inhibition that account for fitness costs and the biochemical activity or inactivity of drug-enzyme complexes. Thus, target overexpression confers resistance or sensitivity as a predictable property of drug mechanism, explaining its variable presence in nature as a resistance mechanism. Though overexpression screens may fail at identifying unknown targets, overexpressing known or putative targets provides a systematic approach to distinguish between simple inhibition and complex mechanisms of drug action.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Palmer AC,Kishony Rdoi
10.1038/ncomms5296subject
Has Abstractpub_date
2014-07-01 00:00:00pages
4296issn
2041-1723pii
ncomms5296journal_volume
5pub_type
杂志文章abstract::Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK c...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03618-w
更新日期:2018-03-23 00:00:00
abstract::How sleep influences brain plasticity is not known. In particular, why certain electroencephalographic (EEG) rhythms are linked to memory consolidation is poorly understood. Calcium activity in dendrites is known to be necessary for structural plasticity changes, but this has never been carefully examined during sleep...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00735-w
更新日期:2017-09-25 00:00:00
abstract::During stress, prompt export of stress-inducible transcripts is critical for cell survival. Here, we characterize a function of the SAGA (Spt-Ada-Gcn5 acetyltransferase) deubiquitylating module (DUBm) in monitoring messenger ribonucleoprotein (mRNP) biogenesis to regulate non-canonical mRNA export of stress-inducible ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10350-6
更新日期:2019-06-05 00:00:00
abstract::Changes in cellular metabolism are associated with the activation of diverse immune subsets. These changes are fuelled by nutrients including glucose, amino acids and fatty acids, and are closely linked to immune cell fate and function. An emerging concept is that nutrients are not equally available to all immune cell...
journal_title:Nature communications
pub_type: 杂志文章,评审
doi:10.1038/s41467-019-10015-4
更新日期:2019-05-09 00:00:00
abstract::As an in-plane charge current flows in a heavy metal film with spin-orbit coupling, it produces a torque on and thereby switches the magnetization in a neighbouring ferromagnetic metal film. Such spin-orbit torque (SOT)-induced switching has been studied extensively in recent years and has shown higher efficiency than...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12688
更新日期:2016-09-01 00:00:00
abstract::Pathological amino-acid substitutions in the amyloid precursor protein (APP) and chemical γ-secretase modulators affect the processing of APP by the γ-secretase complex and the production of the amyloid-beta peptide Aβ42, the accumulation of which is considered causative of Alzheimer's disease. Here we demonstrate tha...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3246
更新日期:2013-01-01 00:00:00
abstract::Purkinje cells (PCs) in Crus 1 represent whisker movement via linear changes in firing rate, but the circuit mechanisms underlying this coding scheme are unknown. Here we examine the role of upstream inputs to PCs-excitatory granule cells (GCs) and inhibitory molecular layer interneurons-in processing of whisking sign...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00312-1
更新日期:2017-08-10 00:00:00
abstract::There are established associations between advanced paternal age and offspring risk for psychiatric and developmental disorders. These are commonly attributed to genetic mutations, especially de novo single nucleotide variants (dnSNVs), that accumulate with increasing paternal age. However, the actual magnitude of ris...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11039-6
更新日期:2019-07-10 00:00:00
abstract::A platform for highly parallel direct sequencing of native RNA strands was recently described by Oxford Nanopore Technologies, but despite initial efforts it remains crucial to further investigate the technology for quantification of complex transcriptomes. Here we undertake native RNA sequencing of polyA + RNA from t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11272-z
更新日期:2019-07-31 00:00:00
abstract::Many of the largest known viruses belong to the PRD1-adeno structural lineage characterised by conserved pseudo-hexameric capsomers composed of three copies of a single major capsid protein (MCP). Here, by high-resolution cryo-EM analysis, we show that a class of archaeal viruses possess hetero-hexameric MCPs which mi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-09451-z
更新日期:2019-03-29 00:00:00
abstract::Human height is a representative phenotype to elucidate genetic architecture. However, the majority of large studies have been performed in European population. To investigate the rare and low-frequency variants associated with height, we construct a reference panel (N = 3,541) for genotype imputation by integrating t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12276-5
更新日期:2019-09-27 00:00:00
abstract::Supercooled liquids exhibit spatial heterogeneity in the dynamics of their fluctuating atomic arrangements. The length and time scales of the heterogeneous dynamics are central to the glass transition and influence nucleation and growth of crystals from the liquid. Here, we report direct experimental visualization of ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03604-2
更新日期:2018-03-19 00:00:00
abstract::Non-aromatic nitrogen- and oxygen-containing heterocycles such as piperidines and pyrans are prevalent components of natural products and pharmaceutical drugs. Although it has been a workhorse as a synthetic method for assembling unsaturated sp(2)-hybridized substrates, transition metal-catalysed cross-coupling chemis...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6474
更新日期:2014-11-18 00:00:00
abstract::A long-standing and profound problem in astronomy is the difficulty in obtaining deep near-infrared observations due to the extreme brightness and variability of the night sky at these wavelengths. A solution to this problem is crucial if we are to obtain the deepest possible observations of the early Universe, as red...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1584
更新日期:2011-12-06 00:00:00
abstract::The diversity of life and its organization in networks of interacting species has been a long-standing theoretical puzzle for ecologists. Ever since May's provocative paper challenging whether 'large complex systems [are] stable' various hypotheses have been proposed to explain when stability should be the rule, not t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12457
更新日期:2016-08-24 00:00:00
abstract::Real-time imaging of moving organs and tissues at microscopic resolutions represents a major challenge in studying the complex biology of live animals. Here we present a technique based on a novel stabilizer setup combined with a gating acquisition algorithm for the imaging of a beating murine heart at the single-cell...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2060
更新日期:2012-01-01 00:00:00
abstract::Plasmodium parasites are obligate intracellular protozoa and causative agents of malaria, responsible for half a million deaths each year. The lifecycle progression of the parasite is reliant on cell motility, a process driven by myosin A, an unconventional single-headed class XIV molecular motor. Here we demonstrate ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11120-0
更新日期:2019-07-23 00:00:00
abstract::The central issue in the physics of cuprate superconductivity is the mutual relationship among superconductivity, pseudogap and broken-spatial-symmetry states. A magnetic field B suppresses superconductivity, providing an opportunity to investigate the competition among these states. Although various B-induced electro...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11747
更新日期:2016-05-27 00:00:00
abstract::The reversible modification of cysteine residues by thioester formation with palmitate (S-palmitoylation) is an abundant lipid post-translational modification (PTM) in mammalian systems. S-palmitoylation has been observed on mitochondrial proteins, providing an intriguing potential connection between metabolic lipids ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02655-1
更新日期:2018-01-23 00:00:00
abstract::Rheb is a small GTP-binding protein and its GTPase activity is activated by the complex of Tsc1 and Tsc2 whose mutations cause tuberous sclerosis complex (TSC). We previously reported that cultured TSC neurons showed impaired spine synapse morphogenesis in an mTORC1-independent manner. Here we show that the PDZ protei...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms7842
更新日期:2015-04-16 00:00:00
abstract::To reconstruct the evolutionary origin of multicellular animals from their unicellular ancestors, the genome sequences of diverse unicellular relatives are essential. However, only the genome of the choanoflagellate Monosiga brevicollis has been reported to date. Here we completely sequence the genome of the filastere...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3325
更新日期:2013-01-01 00:00:00
abstract::Monolayer chalcogenide semiconductors with both luminescent and ferromagnetic properties are dreamed for simultaneous polarization and detection of the valley degree of freedom in valleytronics. However, a conventional chalcogenide monolayer lacks these coexisting properties due to their mutually exclusive origins. He...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-09531-0
更新日期:2019-04-05 00:00:00
abstract::Central nervous system (CNS) injuries persist for years, and currently there are no therapeutics that can address the complex injury cascade that develops over this time-scale. 17β-estradiol (E2) has broad tropism within the CNS, targeting and inducing beneficial phenotypic changes in myriad cells following injury. To...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12835-w
更新日期:2019-10-23 00:00:00
abstract::Type 2 diabetes mellitus (T2DM) is characterized by defects in both insulin sensitivity and glucose-stimulated insulin secretion (GSIS) and is often accompanied by obesity. In this study, we show that disruption of thioredoxin binding protein-2 (TBP-2, also called Txnip) in obese mice (ob/ob) dramatically improves hyp...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1127
更新日期:2010-11-23 00:00:00
abstract::In response to brain injury, microglia rapidly extend processes that isolate lesion sites and protect the brain from further injury. Here we report that microglia carrying a pathogenic mutation in the Parkinson's disease (PD)-associated gene, G2019S-LRRK2 (GS-Tg microglia), show retarded ADP-induced motility and delay...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9255
更新日期:2015-09-14 00:00:00
abstract::Tumour-associated macrophages (TAMs) play an important role in tumour progression, which is facilitated by their ability to respond to environmental cues. Here we report, using murine models of breast cancer, that TAMs expressing fibroblast activation protein alpha (FAP) and haem oxygenase-1 (HO-1), which are also fou...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05346-7
更新日期:2018-07-27 00:00:00
abstract::A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single sp...
journal_title:Nature communications
pub_type: 历史文章,杂志文章
doi:10.1038/s41467-018-06695-z
更新日期:2018-11-16 00:00:00
abstract::Collective cell migration mediates multiple tissue morphogenesis processes. Yet how multi-dimensional mesenchymal cell movements are coordinated remains mostly unknown. Here we report that coordinated mesenchymal cell migration during chicken feather elongation is accompanied by dynamic changes of bioelectric currents...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07661-5
更新日期:2018-12-18 00:00:00
abstract::Nematode neurons generally produce graded potentials instead of action potentials. It is unclear how the graded potentials control postsynaptic cells under physiological conditions. Here we show that postsynaptic currents frequently occur in bursts at the neuromuscular junction of Caenorhabditis elegans. Cholinergic b...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2925
更新日期:2013-01-01 00:00:00
abstract::The emergence of antibiotic resistant bacteria is a major threat to the practice of modern medicine. Photobactericidal agents have obtained significant attention as promising candidates to kill bacteria, and they have been extensively studied. However, to obtain photobactericidal activity, an intense white light sourc...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15004-6
更新日期:2020-03-05 00:00:00