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Book chapterErrington E, Guo M, Heng JYY, 2022,
Environmental Impacts of Rice Husk-Derived Silica under Uncertainty: Is “Bio” better?
, Computer Aided Chemical Engineering, Pages: 1615-1620Millions of tonnes of rice husk (RH) are produced annually as an agricultural waste. One area of interest for RH valorisation is to use rice husk ash (RHA, a by-product of RH combustion) as a replacement for mineral-derived synthetic amorphous silica (M-SAS). However, little information is available on the environmental benefit of this approach. This study details the first evaluation of the environmental benefits of producing RH-derived synthetic amorphous silica (RH-SAS). This is done by describing the life cycle of RH-SAS in terms of stages for which existing life cycle inventories can be linked and aggregated in a modular way. It is then shown how the physical meaning of linkages between modules are governed by both the characteristics of the RH feedstock and efficiencies of processes across the life cycle. To provide more robust findings, the sensitivity of predictions to model uncertainty are also considered. Finally, a case is provided for the benefit of RH-SAS production within the Asia-Pacific (APAC) SAS market.
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Journal articleMaertens GN, Engelman AN, Cherepanov P, 2022,
Structure and function of retroviral integrase
, Nature Reviews Microbiology, Vol: 20, Pages: 20-34, ISSN: 1740-1526A hallmark of retroviral replication is establishment of the proviral state, wherein a DNA copy of the viral RNA genome is stably incorporated into a host cell chromosome. Integrase is the viral enzyme responsible for the catalytic steps involved in this process, and integrase strand transfer inhibitors are widely used to treat people living with HIV. Over the past decade, a series of X-ray crystallography and cryogenic electron microscopy studies have revealed the structural basis of retroviral DNA integration. A variable number of integrase molecules congregate on viral DNA ends to assemble a conserved intasome core machine that facilitates integration. The structures additionally informed on the modes of integrase inhibitor action and the means by which HIV acquires drug resistance. Recent years have witnessed the development of allosteric integrase inhibitors, a highly promising class of small molecules that antagonize viral morphogenesis. In this Review, we explore recent insights into the organization and mechanism of the retroviral integration machinery and highlight open questions as well as new directions in the field.
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Journal articlePalmas MF, Ena A, Burgaletto C, et al., 2022,
Repurposing Pomalidomide as a Neuroprotective Drug: Efficacy in an Alpha-Synuclein-Based Model of Parkinson's Disease
, NEUROTHERAPEUTICS, Vol: 19, Pages: 305-324, ISSN: 1933-7213- Author Web Link
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- Citations: 2
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Journal articleLalvani A, Hakki S, Singanayagam A, et al., 2022,
Transmissibility of SARS-CoV-2 among fully vaccinated individuals reply
, LANCET INFECTIOUS DISEASES, Vol: 22, Pages: 18-19, ISSN: 1473-3099- Author Web Link
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- Citations: 1
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Journal articleVelasco PQ, Karde V, Ito Y, et al., 2022,
Rational synthesis of polymer coated inorganic nanoparticles-MWCNT hybrids via solvophobic effects
, CARBON TRENDS, Vol: 6, ISSN: 2667-0569 -
Journal articleKarde V, Jefferson AE, Hebbink GA, et al., 2022,
Investigating sizing induced surface alterations in crystalline powders using surface energy heterogeneity determination
, Powder Technology, Vol: 395, Pages: 645-651, ISSN: 0032-5910Particle sizing is the most commonly employed and critical unit operation across powder processing industries. In this work, we show the surface energy changes prompted by the sizing operations like milling and sieving in α-lactose monohydrate powders using Finite Dilution Inverse gas chromatography (FD-IGC) analysis. Three separate sieved fractions of α-lactose monohydrate powder were divided into a top, middle and bottom fraction from the same starting material. Similarly, a custom grade α-lactose monohydrate was milled for a different duration to produce two milled samples with different median particle sizes. Sieved sample results showed that the bottom fraction exhibited higher heterogeneity with higher dispersive (γd) surface energy values ranging from 42.5 mJ/m2 to 45.9 mJ/m2 compared to the top and middle fractions. The finest fraction contains more cleaved surfaces that are exposed during the preparation process, i.e. milling, of the material resulting in different surface properties. Furthermore, the surface energy analysis of the milled samples revealed slight but vital differences in the γd heterogeneity profiles. The site-specific distribution of energies was obtained using the Boltzmann probability distribution model and revealed two distinct regions for crystalline α-lactose monohydrate. Thus, our work confirmed that sizing operations like milling and sieving affect the surface energy of the particulate solids due to the changes in properties like size, shape, exposure of internal cleavage planes, etc. and that the surface energy heterogeneity determination using FD-IGC helped in characterising these changes.
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Journal articleKaramanos TK, Clore GM, 2022,
Large Chaperone Complexes Through the Lens of Nuclear Magnetic Resonance Spectroscopy
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Journal articleCawood EE, Clore GM, Karamanos TK, 2022,
Microsecond Backbone Motions Modulate the Oligomerization of the DNAJB6 Chaperone
, Angewandte Chemie International Edition, Vol: 61, ISSN: 1433-7851 -
Journal articleKaramanos TK, Kalverda AP, Radford SE, 2022,
Generating ensembles of dynamic misfolding proteins
, Frontiers in Neuroscience, Vol: 16 -
Journal articleDavidson M, Andradi-Brown C, Yahiya S, et al., 2022,
Automated detection and staging of malaria parasites from cytological smears using convolutional neural networks
, Biological Imaging, Vol: 1, Pages: 1-13, ISSN: 2633-903XMicroscopic examination of blood smears remains the gold standard for laboratory inspection and diagnosis of malaria. Smear inspection is, however, time consuming and dependent on trained microscopists with results varying in accuracy. We sought to develop an automated image analysis method to improve accuracy and standardisation of smear inspection that retains capacity for expert confirmation and image archiving. Here we present a machine-learning method that achieves red blood cell (RBC) detection, differentiation between infected/uninfected cells and parasite life stage categorisation from unprocessed, heterogeneous smear images. Based on a pre-trained Faster Region-Based Convolutional Neural Networks (R-CNN) model for RBC detection, our model performs accurately, with average precision of 0.99 at an intersection-over-union threshold of 0.5. Application of a residual neural network (ResNet)-50 model to infected cells also performs accurately, with an area under the receiver operating characteristic curve of 0.98. Lastly, combining our method with a regression model successfully recapitulates intra-erythrocytic developmental cycle with accurate lifecycle stage categorisation. Combined with a mobile-friendly web-based interface, called PlasmoCount, our method permits rapid navigation through and review of results for quality assurance. By standardising assessment of Giemsa smears, our method markedly improves inspection reproducibility and presents a realistic route to both routine lab but also future field-based automated malaria diagnosis.
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Journal articleKennedy A, Griffin G, Freemont PS, et al., 2022,
A curcumin direct protein biosensor for cell-free prototyping.
, Eng Biol, Vol: 6, Pages: 62-68In synthetic biology, biosensors are routinely coupled with a gene expression system for detecting small molecules and physical signals. We reveal a fluorescent complex, based on the interaction of an Escherichia coli double bond reductase (EcCurA), as a detection unit with its substrate curcumin-we call this a direct protein (DiPro) biosensor. Using a cell-free synthetic biology approach, we use the EcCurA DiPro biosensor to fine tune 10 reaction parameters (cofactor, substrate, and enzyme levels) for cell-free curcumin biosynthesis, assisted through acoustic liquid handling robotics. Overall, we increase EcCurA-curcumin DiPro fluorescence within cell-free reactions by 78-fold. This finding adds to the growing family of protein-ligand complexes that are naturally fluorescent and potentially exploitable for a range of applications, including medical imaging to engineering high-value chemicals.
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Book chapterFilloux A, Ramos J-L, 2022,
<i>Pseudomonas aeruginosa</i> Biology, Pathogenesis and Control Strategies Preface
, PSEUDOMONAS AERUGINOSA, Editors: Filloux, Ramos, Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: V-X, ISBN: 978-3-031-08490-4 -
Journal articleSarkar K, Joedicke L, Westwood M, et al., 2022,
Modulation of PTH1R signaling by an extracellular binding antibody
, PARATHYROID HORMONE, Vol: 120, Pages: 109-132, ISSN: 0083-6729 -
Journal articleSchiffrin B, Machin JM, Karamanos T, et al., 2022,
Dynamic interplay between the periplasmic chaperone SurA and the BAM complex in outer membrane protein folding
, Communications Biology, ISSN: 2399-3642 -
Working paperKumar A, Zhang X, Vadas O, et al., 2021,
Secondary structure and X-Ray crystallographic analysis of the Glideosome-Associated Connector (GAC) from toxoplasma gondii
, Publisher: PreprintsA model for parasitic motility has been proposed in which parasite filamentous actin (F-actin) is attached to surface adhesins by a large component of the glideosome, known as the glideosome-associated connector protein (GAC). This large 286 kDa protein interacts at the cytoplasmic face of the plasma membrane with the phosphatidic acid-enriched inner leaflet and cytosolic tails of surface adhesins to connect them to the parasite actomyosin system. GAC is observed initially to the conoid at the apical pole and re-localised with the glideosome to the basal pole in gliding parasite. GAC presumably functions in force transmission to surface adhesins in the plasma membrane and not in force generation. Proper connection between F-actin and the adhesins is as important for motility and invasion as motor operation itself. This notion highlights the need for new structural information on GAC interactions, which has eluded the field since its discovery. We have obtained crystals that diffracted to 2.6-2.9 Å for full-length GAC from Toxoplasma gondii in native and selenomethionine-labelled forms. These crystals belong to space group P212121, cell dimensions are roughly a=119 Å, b=123Å, c=221Å, α=90, β=90, γ=90 with 1 molecule per asymmetric unit, suggesting a more compact conformation than previously proposed.
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Journal articleLi X, Heng JYY, 2021,
Protein crystallisation facilitated by silica particles to compensate for the adverse impact from protein impurities
, CrystEngComm, Vol: 23, Pages: 8386-8391, ISSN: 1466-8033In this study, silica particles were used to improve target protein batch crystallisation from a binary protein mixture at a 5 mL scale. Lysozyme (40 mg mL−1) was used as the target protein and thaumatin (0.1–8 mg mL−1) was regarded as a protein impurity. It was demonstrated that even an impurity at the concentration as low as 0.1 mg mL−1 (0.25 w/w% of the target protein) would delay target protein crystallisation, predominantly by extending the induction time. When the silica particles were employed in the system to facilitate crystallisation, target protein crystallisation was significantly improved with a much shorter induction time and higher yield at the end of the experiment. It was also shown that the effectiveness of silica on target protein crystallisation depended on the impurity concentration and silica loading amount.
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Journal articleJamshidiha M, Lanyon-Hogg T, Sutherell C, et al., 2021,
Identification of the first structurally validated covalent ligands of the small GTPase RAB27A
, RSC Medicinal Chemistry, Vol: 13, Pages: 150-155, ISSN: 2632-8682Rab27A is a small GTPase, which mediates transport and docking of secretory vesicles at the plasma membrane via protein–protein interactions (PPIs) with effector proteins. Rab27A promotes the growth and invasion of multiple cancer types such as breast, lung and pancreatic, by enhancing secretion of chemokines, metalloproteases and exosomes. The significant role of Rab27A in multiple cancer types and the minor role in adults suggest that Rab27A may be a suitable target to disrupt cancer metastasis. Similar to many GTPases, the flat topology of the Rab27A-effector PPI interface and the high affinity for GTP make it a challenging target for inhibition by small molecules. Reported co-crystal structures show that several effectors of Rab27A interact with the Rab27A SF4 pocket (‘WF-binding pocket’) via a conserved tryptophan–phenylalanine (WF) dipeptide motif. To obtain structural insight into the ligandability of this pocket, a novel construct was designed fusing Rab27A to part of an effector protein (fRab27A), allowing crystallisation of Rab27A in high throughput. The paradigm of KRas covalent inhibitor development highlights the challenge presented by GTPase proteins as targets. However, taking advantage of two cysteine residues, C123 and C188, that flank the WF pocket and are unique to Rab27A and Rab27B among the >60 Rab family proteins, we used the quantitative Irreversible Tethering (qIT) assay to identify the first covalent ligands for native Rab27A. The binding modes of two hits were elucidated by co-crystallisation with fRab27A, exemplifying a platform for identifying suitable lead fragments for future development of competitive inhibitors of the Rab27A-effector interaction interface, corroborating the use of covalent libraries to tackle challenging targets.
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Journal articleRattu P, Glencross F, Mader SL, et al., 2021,
Atomistic level characterisation of ssDNA translocation through the E. coli proteins CsgG and CsgF for nanopore sequencing
, Computational and Structural Biotechnology Journal, Vol: 19, Pages: 6417-6430, ISSN: 2001-0370Two proteins of the Escherichia coli membrane protein complex, CsgG and CsgF, are studied as proteinaceous nanopores for DNA sequencing. It is highly desirable to control the DNA as it moves through the pores, this requires characterisation of DNA translocation and subsequent optimization of the pores. In order to inform protein engineering to improve the pores, we have conducted a series of molecular dynamics simulations to characterise the mechanical strength and conformational dynamics of CsgG and the CsgG-CsgF complex and how these impact ssDNA, water and ion movement. We find that the barrel of CsgG is more susceptible to damage from external electric fields compared to the protein vestibule. Furthermore, the presence of CsgF within the CsgG-CsgF complex enables the complex to withstand higher electric fields. We find that the eyelet loops of CsgG play a key role in both slowing the translocation rate of DNA and modulating the conductance of the pore. CsgF also impacts the DNA translocation rate, but to a lesser degree than CsgG.
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Journal articleSanchez Garrido J, Alberdi L, Chatterjee S, et al., 2021,
Type III secretion system effector subnetworks elicit distinct host immune responses to infection
, Current Opinion in Microbiology, Vol: 64, Pages: 19-26, ISSN: 1369-5274Citrobacter rodentium, a natural mouse pathogen which colonises the colon of immuno-competent mice, provides a robust model for interrogating host-pathogen-microbiota interactions in vivo. This model has been key to providing new insights into local host responses to enteric infection, including changes inintestinal epithelial cell immuno metabolism and mucosal immunity. C. rodent iuminjects 31 bacterial effectors into epithelial cells via a type III secretion system (T3SS). Recently, these effectors were shown to be able to form multiple intracellular subnetworks which can withstand significant contractions whilst maintaining virulence. Here we highlight recent advances in understanding gut mucosal responses to infection and effector biology, as well as potential uses for artificial intelligence (AI) in understanding infectious diseaseand speculate on the role of T3SS effector networks in host adaption.
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Journal articleHan P, Go MK, Chow JY, et al., 2021,
A high-throughput pipeline for scalable kit-free RNA extraction
, Scientific Reports, Vol: 11, Pages: 1-10, ISSN: 2045-2322An overreliance on commercial, kit-based RNA extraction in the molecular diagnoses of infectious disease presents a challenge in the event of supply chain disruptions and can potentially hinder testing capacity in times of need. In this study, we adapted a well-established, robust TRIzol-based RNA extraction protocol into a high-throughput format through miniaturization and automation. The workflow was validated by RT-qPCR assay for SARS-CoV-2 detection to illustrate its scalability without interference to downstream diagnostic sensitivity and accuracy. This semi-automated, kit-free approach offers a versatile alternative to prevailing integrated solid-phase RNA extraction proprietary systems, with the added advantage of improved cost-effectiveness for high volume acquisition of quality RNA whether for use in clinical diagnoses or for diverse molecular applications.
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Journal articleMolisso S, Williams DR, Ces O, et al., 2021,
Molecular interaction and partitioning in α-Keratin using 1H NMR Spin-Lattice (T1) relaxation times
, Journal of the Royal Society Interface, Vol: 18, Pages: 1-8, ISSN: 1742-5662The interactions between small molecules and keratins are poorly understood. In this paper an NMR method is presented to measure changes in the 1H T1 relaxation times of small molecules in human hair keratin to quantify their interaction with the fiber. Two populations of small molecule compounds were identified with distinct relaxation times, demonstrating the partitioning of the compounds into different keratin environments. The changes in relaxation time for solvent in hair compared to bulk solvent were shown to be related to the molecular weight, MW, and the partition coefficient, LogP, of the solvent investigated. Compounds with low molecular weights and high hydrophilicities had greater reductions in their T1 relaxation times and therefore experienced increased interactions with the hair fiber. The relative population sizes were also calculated. This is a significant step toward modelling the behavior of small molecules in keratinous materials and other large insoluble fibrous proteins.
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Journal articleUmrekar T, Winterborn Y, Sivabalasarma S, et al., 2021,
Evolution of archaellum rotation involved invention of a stator complex by duplicating and modifying a core component
, Frontiers in Microbiology, Vol: 12, Pages: 1-10, ISSN: 1664-302XNovelty in biology can arise from opportunistic repurposing of nascent characteristics ofexisting features. Understanding how this process happens at the molecular scale, however,suffers from a lack of case studies. The evolutionary emergence of rotary motors is aparticularly clear example of evolution of a new function. The simplest of rotary motors is thearchaellum, a molecular motor that spins a helical propeller for archaeal motility analogous tothe bacterial flagellum. Curiously, emergence of archaellar rotation may have pivoted on thesimple duplication and repurposing of a pre-existing component to produce a stator complexthat anchors to the cell superstructure to enable productive rotation of the rotor component.This putative stator complex is composed of ArlF and ArlG, gene duplications of the filamentcomponent ArlB, providing an opportunity to study how gene duplication andneofunctionalization contributed to the radical innovation of rotary function. Towardunderstanding how this happened, we used electron cryomicroscopy to determine thestructure of isolated ArlG filaments, the major component of the stator complex. Using ahybrid modeling approach incorporating structure prediction and validation, we show thatArlG filaments are open helices distinct to the closed helical filaments of ArlB. Curiously,further analysis reveals that ArlG retains a subset of the inter-protomer interactions ofhomologous ArlB, resulting in a superficially different assembly that nevertheless reflects thecommon ancestry of the two structures. This relatively simple mechanism to changequaternary structure was likely associated with the evolutionary neofunctionalization of thearchaellar stator complex, and we speculate that the relative deformable elasticity of an openhelix may facilitate elastic energy storage during the transmission of the discrete bursts ofenergy released by ATP hydrolysis to continuous archaellar rotation, allowing the inherentproperties of a duplicated ArlB to be
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Journal articleAmin H, Ilangovan A, Costa TRD, 2021,
Architecture of the outer-membrane core complex from a conjugative type IV secretion system.
, Nat Commun, Vol: 12Conjugation is one of the most important processes that bacteria utilize to spread antibiotic resistance genes among bacterial populations. Interbacterial DNA transfer requires a large double membrane-spanning nanomachine called the type 4 secretion system (T4SS) made up of the inner-membrane complex (IMC), the outer-membrane core complex (OMCC) and the conjugative pilus. The iconic F plasmid-encoded T4SS has been central in understanding conjugation for several decades, however atomic details of its structure are not known. Here, we report the structure of a complete conjugative OMCC encoded by the pED208 plasmid from E. coli, solved by cryo-electron microscopy at 3.3 Å resolution. This 2.1 MDa complex has a unique arrangement with two radial concentric rings, each having a different symmetry eventually contributing to remarkable differences in protein stoichiometry and flexibility in comparison to other OMCCs. Our structure suggests that F-OMCC is a highly dynamic complex, with implications for pilus extension and retraction during conjugation.
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Journal articleVidal LS, Murray JW, Heap JT, 2021,
Versatile selective evolutionary pressure using synthetic defect in universal metabolism
, Nature Communications, Vol: 12, Pages: 1-15, ISSN: 2041-1723Versatile selective evolutionary pressure using synthetic defect in universal metabolism
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Journal articleBrady A, Quiles-Puchalt, Gallego del Sol F, et al., 2021,
The arbitrium system controls prophage induction
, Current Biology, Vol: 31, Pages: 5037-5045, ISSN: 0960-9822Some Bacillus-infecting bacteriophages use a peptide-based communication system, termed arbitrium, to coordinate the lysis-lysogeny decision. In this system the phage produces AimP peptide during the lytic cycle. Once internalised by the host cell, AimP binds to the transcription factor AimR, reducing aimX expression and promoting lysogeny. Although these systems are present in a variety of mobile genetic elements, their role in the phage life cycle has only been characterised in phage phi3T during phage infection. Here, using the B. subtilis SPb prophage, we show that the arbitrium system is also required for normal prophage induction. Deletion of the aimP gene increased phage reproduction, while the aimR deletion significantly reduced the number of phage particles produced after prophage induction. Moreover, our results indicated that AimR is involved in a complex network of regulation and brought forward two new players in the SPb lysis-lysogeny decision system, YopN and the phage repressor YopR. Importantly, these proteins are encoded in an operon, the function of which is conserved across all SPb-like phages encoding the arbitrium system. Finally, we obtained mutant phages in the arbitrium system, which behaved almost identically to the wt phage, indicating that the arbitrium system is not essential in the laboratory but is likely beneficial for phage fitness in nature. In support of this, by possessing a functional arbitrium system the SPb phage can optimise production of infective particles whilst also preserving the number of cells that survive after prophage induction, a strategy that increases phage persistence in nature.
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Journal articleMercer T, Almond N, Chain P, et al., 2021,
A roadmap to better COVID-19 testing from the Coronavirus Standards Working Group
<title>Abstract</title> <p>Testing has been central to our response to the COVID-19 pandemic. However, the accuracy of testing relies on standards, including reference materials, proficiency testing schemes, and information and reporting guidelines. The use of standards is a simple, inexpensive, and effective method to ensure reliable test results that inform clinical and public health decisions. Here we describe the central role of standards during the COVID-19 pandemic, where they have enabled population-scale screening, genomic surveillance and measures of immune protection measures. Given these benefits, the Coronavirus Standards Working Group (CSWG) was formed to coordinate standards in SARS-CoV-2 testing. This network of scientists has developed best-practices, reference materials, and conducted proficiency studies to harmonize laboratory performance. We propose that this coordinated development of standards should be prioritized as a key early step in the public health response to future pandemics that is necessary for reliable, large-scale testing for infectious disease.</p>
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Journal articleHumphrey S, Fillol-Salom A, Quiles-Puchalt N, et al., 2021,
Bacterial chromosomal mobility via lateral transduction exceeds that of classical mobile genetic elements
, Nature Communications, Vol: 12, Pages: 1-12, ISSN: 2041-1723It is commonly assumed that the horizontal transfer of most bacterial chromosomal genes is limited, in contrast to the frequent transfer observed for typical mobile genetic elements. However, this view has been recently challenged by the discovery of lateral transduction in Staphylococcus aureus, where temperate phages can drive the transfer of large chromosomalregions at extremely high frequencies. Here, we analyse previously published as well as new datasets to compare horizontal gene transfer rates mediated by different mechanisms in S. aureus and Salmonella enterica. We find that the horizontal transfer of core chromosomal genes via lateral transduction can be more efficient than the transfer of classical mobile genetic elements via conjugation or generalized transduction. These results raise questions about our definition of mobile genetic elements, and the potential roles played by lateral transduction in bacterial evolution.
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Journal articleHutchison CDM, Parker S, Chukhutsina V, et al., 2021,
Open hardware microsecond dispersive transient absorption spectrometer for linear optical response
, Photochemical and Photobiological Sciences, Vol: 21, Pages: 23-35, ISSN: 1474-905XAn open hardware design and implementation for a transient absorption spectrometer are presented that has microsecond time resolution and measures full difference spectra in the visible spectral region from 380 to 750 nm. The instrument has been designed to allow transient absorption spectroscopy measurements of either low or high quantum yield processes by combining intense sub-microsecond excitation flashes using a xenon lamp together with stroboscopic non-actinic white light probing using LED sources driven under high pulsed current from a capacitor bank. The instrument is sensitive to resolve 0.15 mOD flash-induced differences within 1000 measurements at 20 Hz repetition rate using an inexpensive CCD sensor with 200 μm pixel dimension, 40 K electrons full well capacity and a dynamic range of 1800. The excitation flash has 230 ns pulse duration and the 2 mJ flash energy allows spectral filtering while retaining high power density with focussing to generate mOD signals in the 10–4–10–1 ΔOD range. We present the full electronics design and construction of the flash and probe sources, the optics as well as the timing electronics and CCD spectrometer operation and modification for internal signal referencing. The performance characterisation and example measurements are demonstrated using microsecond TAS of Congo red dye, as an example of a low quantum yield photoreaction at 2% with up to 78% of molecules excited. The instrument is fully open hardware and combines inexpensive selection of commercial components, optics and electronics and allows linear response measurements of photoinduced reactions for the purpose of accurate global analysis of chemical dynamics.
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Journal articleFillol-Salom A, Bacigalupe R, Humphrey S, et al., 2021,
Lateral transduction is inherent to the life cycle of the archetypical Salmonella phage P22
, Nature Communications, Vol: 12, Pages: 1-11, ISSN: 2041-1723Lysogenic induction ends the stable association between a bacteriophage and its host, andthe transition to the lytic cycle begins with early prophage excision followed by DNA replication and packaging (ERP). This temporal program is considered universal for P22-liketemperate phages, though there is no direct evidence to support the timing and sequence ofthese events. Here we report that the long-standing ERP program is an observation of theexperimentally favored Salmonella phage P22 tsc229 heat-inducible mutant, and that wildtype P22 actually follows the replication-packaging-excision (RPE) program. We find that P22tsc229 excises early after induction, but P22 delays excision to just before it is detrimental tophage production. This allows P22 to engage in lateral transduction. Thus, at minimalexpense to itself, P22 has tuned the timing of excision to balance propagation with lateraltransduction, powering the evolution of its host through gene transfer in the interest of selfpreservation.
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Journal articleLiu B, Li S, Liu Y, et al., 2021,
Bacteriophage Twort protein Gp168 is a β-clamp inhibitor by occupying the DNA sliding channel
, NUCLEIC ACIDS RESEARCH, Vol: 49, Pages: 11367-11378, ISSN: 0305-1048- Cite
- Citations: 12
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