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Record W2913227771 · doi:10.1038/s42003-019-0297-6

Membrane charge and lipid packing determine polymyxin-induced membrane damage

2019· article· en· W2913227771 on OpenAlex
Adree Khondker, Alexander Dhaliwal, Sokunthearath Saem, Ahmad Mahmood, Cécile Fradin, Jose Moran‐Mirabal, Maikel C. Rheinstädter

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueCommunications Biology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAntibiotic Resistance in Bacteria
Canadian institutionsMcMaster University
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchMinistero dello Sviluppo EconomicoOntario Ministry of Economic Development and InnovationMcMaster University
KeywordsMembranePenetration (warfare)BiophysicsBacterial outer membraneLipid bilayerChemistryMaterials scienceSurface chargeTransmembrane proteinMembrane potentialMolecular dynamicsBiochemistryBiologyComputational chemistry

Abstract

fetched live from OpenAlex

Abstract With the advent of polymyxin B (PmB) resistance in bacteria, the mechanisms for mcr -1 resistance are of crucial importance in the design of novel therapeutics. The mcr -1 phenotype is known to decrease membrane charge and increase membrane packing by modification of the bacterial outer membrane. We used X-ray diffraction, Molecular Dynamics simulations, electrochemistry, and leakage assays to determine the location of PmB in different membranes and assess membrane damage. By varying membrane charge and lipid tail packing independently, we show that increasing membrane surface charge promotes penetration of PmB and membrane damage, whereas increasing lipid packing decreases penetration and damage. The penetration of the PmB molecules is well described by a phenomenological model that relates an attractive electrostatic and a repulsive force opposing insertion due to increased membrane packing. The model applies well to several gram-negative bacterial strains and may be used to predict resistance strength.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.175
Threshold uncertainty score0.683

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.288
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it