Visualizing Science Fiction and relating it to Science Fact

Cornea, Christine; Bowater, Laura; Bowater, Richard P.

doi:10.1042/bio03406004

Cited by 3 publications

(2 citation statements)

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“…Currently the world faces an emerging antibiotic resistance crisis because the rate of developing new antibiotics has not caught up with the pace of the spread of antibiotic resistance. , This is caused by several factors: antibiotic resistance is an ancient evolutionary phenomenon and is unavoidable, , while the small number of novel antibiotics entering the market might be partly caused by the limitations of existing compound libraries used in the pharmaceutical industry and the possible lack of unexplored, “low-hanging-fruit” drug classes , (but see also ref ). Socioeconomic factors also contribute, including the irresponsible use of antibiotics promoting resistance and the relatively low profitability of novel antimicrobials, which, exactly to prevent the emergence of resistance, are likely to be used as last-resort drugs rather than first-line medications.…”

Section: Introductionmentioning

confidence: 99%

Ligands and Receptors with Broad Binding Capabilities Have Common Structural Characteristics: An Antibiotic Design Perspective

Abrusán

Marsh

2019

J. Med. Chem.

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The spread of antibiotic resistance is one of the most serious global public-health problems. Here we show that a particular class of homomers with binding sites spanning multiple protein chains is particularly suitable for targeting by broad-spectrum antibacterial agents because due to the slow evolutionary change of such binding pockets, ligands of such homomers are much more likely to bind their homologs than ligands of monomers, or homomers with a single-chain binding site. Additionally, using de novo ligand design and deep learning, we show that the chemical compounds that can bind several different receptors have common structural characteristics and that halogens and fragments similar to the building blocks existing antimicrobials are overrepresented in them. Finally, we show that binding multiple receptors selects for flexible compounds, which are less likely to accumulate in Gram-negative bacteria; thus there is trade-off between reducing the emergence of resistance by multitargeting and broad-spectrum antibacterial activity.

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Section: Introductionmentioning

confidence: 99%

Ligands and Receptors with Broad Binding Capabilities Have Common Structural Characteristics: An Antibiotic Design Perspective

Abrusán

Marsh

2019

J. Med. Chem.

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“…This work demonstrates that both bacterial concentration and water turbulence can be influential in determining the relative importance of conjugation versus phage delivery of ARGs, with the latter reaching comparable transfer frequencies at relatively low cell concentrations under either quiescent or turbulent conditions that hinder conjugation. Accordingly, ARG transfer via phages may become relatively important in oligotrophic aquatic systems (Figure S5) not only due to low bacterial concentration but also because phage transfer is less energy intensive than conjugation ,− and thus it is potentially less susceptible to lower energy source availability.…”

Section: Results and Discussionmentioning

confidence: 99%

Bacterial Concentrations and Water Turbulence Influence the Importance of Conjugation Versus Phage-Mediated Antibiotic Resistance Gene Transfer in Suspended Growth Systems

Sun

Zuo

et al. 2021

ACS Environ. Au

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Despite the abundance of phage-borne antibiotic resistance genes (ARGs) in the environment, the frequency of ARG propagation via phage-mediated transduction (relative to via conjugation) is poorly understood. We investigated the influence of bacterial concentration and water turbulence level [quantified as Reynold's number (Re)] in suspended growth systems on the frequency of ARG transfer by two mechanisms: delivery by a lysogenic phage (phage λ carrying gentamycin-resistance gene, genR) and conjugation mediated by the self-transmissible plasmid RP4. Using Escherichia coli (E. coli) as the recipient, phage delivery had a comparable frequency (1.2 ± 0.9 × 10 −6 ) to that of conjugation (1.1 ± 0.9 × 10 −6 ) in suspensions with low cell concentration (10 4 CFU/mL) and moderate turbulence (Re = 5 × 10 4 ). Turbulence affected cell (or phage)-to-cell contact rates and detachment (due to shear force), and thus, it affected the relative importance of conjugation versus phage delivery. At 10 7 CFU/mL, no significant difference was observed between the frequencies of ARG transfer by the two mechanisms under quiescent water conditions (2.8 ± 0.3 × 10 −5 for conjugation vs 2.2 ± 0.5 × 10 −5 for phage delivery, p = 0.19) or when Re reached 5 × 10 5 (3.4 ± 1.5 × 10 −5 for conjugation vs 2.9 ± 1.0 × 10 −5 for phage delivery, p = 0.52). Transcriptomic analysis of genes related to conjugation and phage delivery and simulation of cell (or phage)-to-cell collisions at different Re values corroborate that the importance of phage delivery relative to conjugation increases under either quiescent or turbulent conditions. This finding challenges the prevailing view that conjugation is the dominant ARG transfer mechanism and underscores the need to consider and mitigate potential ARG dissemination via transduction.

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The End of the World (EOTW) Scientist and the Framing of Science in Science Fiction Films from 1950 to 2010

Lui¹

2015

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Visualizing Science Fiction and relating it to Science Fact

Cited by 3 publications

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Ligands and Receptors with Broad Binding Capabilities Have Common Structural Characteristics: An Antibiotic Design Perspective

Ligands and Receptors with Broad Binding Capabilities Have Common Structural Characteristics: An Antibiotic Design Perspective

Bacterial Concentrations and Water Turbulence Influence the Importance of Conjugation Versus Phage-Mediated Antibiotic Resistance Gene Transfer in Suspended Growth Systems

The End of the World (EOTW) Scientist and the Framing of Science in Science Fiction Films from 1950 to 2010

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