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Cambridge Infectious Diseases

An Interdisciplinary Research Centre at the University of Cambridge
 

Co-evolutionary signals identify Burkholderia pseudomallei survival strategies in a hostile environment

Mon, 18/10/2021 - 11:00

Mol Biol Evol. 2021 Oct 18:msab306. doi: 10.1093/molbev/msab306. Online ahead of print.

ABSTRACT

The soil bacterium Burkholderia pseudomallei is the causative agent of melioidosis and a significant cause of human morbidity and mortality in many tropical and sub-tropical countries. The species notoriously survives harsh environmental conditions but the genetic architecture for these adaptations remains unclear. Here we employed a powerful combination of genome-wide epistasis and co-selection studies (2,011 genomes), condition-wide transcriptome analyses (82 diverse conditions), and a gene knockout assay to uncover signals of "co-selection" - that is a combination of genetic markers that have been repeatedly selected together through B. pseudomallei evolution. These enabled us to identify 13,061 mutation pairs under co-selection in distinct genes and non-coding RNA. Genes under co-selection displayed marked expression correlation when B. pseudomallei was subjected to physical stress conditions, highlighting the conditions as one of the major evolutionary driving forces for this bacterium. We identified a putative adhesin (BPSL1661) as a hub of co-selection signals, experimentally confirmed a BPSL1661 role under nutrient deprivation, and explored the functional basis of co-selection gene network surrounding BPSL1661 in facilitating the bacterial survival under nutrient depletion. Our findings suggest that nutrient-limited conditions have been the common selection pressure acting on this species, and allelic variation of BPSL1661 may have promoted B. pseudomallei survival during harsh environmental conditions by facilitating bacterial adherence to different surfaces, cells, or living hosts.

PMID:34662416 | DOI:10.1093/molbev/msab306

Zika Virus and Neuropathogenesis: The Unanswered Question of Which Strain Is More Prone to Causing Microcephaly and Other Neurological Defects

Mon, 18/10/2021 - 11:00

Front Cell Neurosci. 2021 Sep 30;15:695106. doi: 10.3389/fncel.2021.695106. eCollection 2021.

ABSTRACT

Despite being perceived to be a relatively innocuous pathogen during its circulation in Africa in the 20th century, consequent outbreaks in French Polynesia and Latin America revealed the Zika virus (ZIKV) to be capable of causing severe neurological defects. Foetuses infected with the virus during pregnancy developed a range of pathologies including microcephaly, cerebral calcifications and macular scarring. These are now collectively known as Congenital Zika syndrome (CZS). It has been established that the neuropathogenesis of ZIKV results from infection of neural progenitor cells in the developing cerebral cortex. Following this, two main hypotheses have emerged: the virus causes either apoptosis or premature differentiation of neural progenitor cells, reducing the final number of mature neurons in the cerebral cortex. This review describes the cellular processes which could potentially cause virus induced apoptosis or premature differentiation, leading to speculation that a combination of the two may be responsible for the pathologies associated with ZIKV. The review also discusses which specific lineages of the ZIKV can employ these mechanisms. It has been unclear in the past whether the virus evolved its neurotropic capability following circulation in Africa, or if the virus has always caused microcephaly but public health surveillance in Africa had failed to detect it. Understanding the true neuropathogenesis of ZIKV is key to being prepared for further outbreaks in the future, and it will also provide insight into how neurotropic viruses can cause profound and life-long neurological defects.

PMID:34658789 | PMC:PMC8514627 | DOI:10.3389/fncel.2021.695106

Modeling Brain-Heart Crosstalk Information in Patients with Traumatic Brain Injury

Wed, 13/10/2021 - 11:00

Neurocrit Care. 2021 Oct 12. doi: 10.1007/s12028-021-01353-7. Online ahead of print.

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) is an extremely heterogeneous and complex pathology that requires the integration of different physiological measurements for the optimal understanding and clinical management of patients. Information derived from intracranial pressure (ICP) monitoring can be coupled with information obtained from heart rate (HR) monitoring to assess the interplay between brain and heart. The goal of our study is to investigate events of simultaneous increases in HR and ICP and their relationship with patient mortality..

METHODS: In our previous work, we introduced a novel measure of brain-heart interaction termed brain-heart crosstalks (ctnp), as well as two additional brain-heart crosstalks indicators [mutual information ([Formula: see text]) and average edge overlap (ωct)] obtained through a complex network modeling of the brain-heart system. These measures are based on identification of simultaneous increase of HR and ICP. In this article, we investigated the relationship of these novel indicators with respect to mortality in a multicenter TBI cohort, as part of the Collaborative European Neurotrauma Effectiveness Research in TBI high-resolution work package.

RESULTS: A total of 226 patients with TBI were included in this cohort. The data set included monitored parameters (ICP and HR), as well as laboratory, demographics, and clinical information. The number of detected brain-heart crosstalks varied (mean 58, standard deviation 57). The Kruskal-Wallis test comparing brain-heart crosstalks measures of survivors and nonsurvivors showed statistically significant differences between the two distributions (p values: 0.02 for [Formula: see text], 0.005 for ctnp and 0.006 for ωct). An inverse correlation was found, computed using the point biserial correlation technique, between the three new measures and mortality: - 0.13 for ctnp (p value 0.04), - 0.19 for ωct (p value 0.002969) and - 0.09 for [Formula: see text] (p value 0.1396). The measures were then introduced into the logistic regression framework, along with a set of input predictors made of clinical, demographic, computed tomography (CT), and lab variables. The prediction models were obtained by dividing the original cohort into four age groups (16-29, 30-49, 50-65, and 65-85 years of age) to properly treat with the age confounding factor. The best performing models were for age groups 16-29, 50-65, and 65-85, with the deviance of ratio explaining more than 80% in all the three cases. The presence of an inverse relationship between brain-heart crosstalks and mortality was also confirmed.

CONCLUSIONS: The presence of a negative relationship between mortality and brain-heart crosstalks indicators suggests that a healthy brain-cardiovascular interaction plays a role in TBI.

PMID:34642842 | DOI:10.1007/s12028-021-01353-7

Thrombolytic Enzymes of Microbial Origin: A Review

Wed, 13/10/2021 - 11:00

Int J Mol Sci. 2021 Sep 28;22(19):10468. doi: 10.3390/ijms221910468.

ABSTRACT

Enzyme therapies are attracting significant attention as thrombolytic drugs during the current scenario owing to their great affinity, specificity, catalytic activity, and stability. Among various sources, the application of microbial-derived thrombolytic and fibrinolytic enzymes to prevent and treat vascular occlusion is promising due to their advantageous cost-benefit ratio and large-scale production. Thrombotic complications such as stroke, myocardial infarction, pulmonary embolism, deep venous thrombosis, and peripheral occlusive diseases resulting from blood vessel blockage are the major cause of poor prognosis and mortality. Given the ability of microbial thrombolytic enzymes to dissolve blood clots and prevent any adverse effects, their use as a potential thrombolytic therapy has attracted great interest. A better understanding of the hemostasis and fibrinolytic system may aid in improving the efficacy and safety of this treatment approach over classical thrombolytic agents. Here, we concisely discuss the physiological mechanism of thrombus formation, thrombo-, and fibrinolysis, thrombolytic and fibrinolytic agents isolated from bacteria, fungi, and algae along with their mode of action and the potential application of microbial enzymes in thrombosis therapy.

PMID:34638809 | DOI:10.3390/ijms221910468

RNA-sequencing elucidates drug-specific mechanisms of antibiotic tolerance and resistance in <em>M. abscessus</em>

Mon, 11/10/2021 - 11:00

Antimicrob Agents Chemother. 2021 Oct 11:AAC0150921. doi: 10.1128/AAC.01509-21. Online ahead of print.

ABSTRACT

Mycobacterium abscessus is an opportunistic pathogen notorious for its resistance to most classes of antibiotics and low cure rates. M. abscessus carries an array of mostly unexplored defence mechanisms. A deeper understanding of antibiotic resistance and tolerance mechanisms is pivotal in development of targeted therapeutic regimens. We provide the first description of all major transcriptional mechanisms of tolerance to all antibiotics recommended in current guidelines, using RNA sequencing-guided experiments. M. abscessus ATCC 19977 bacteria were subjected to sub-inhibitory concentrations of clarithromycin, amikacin, tigecycline, cefoxitin and clofazimine for 4- and 24-hours, followed by RNA sequencing. To confirm key mechanisms of tolerance suggested by transcriptomic responses, we performed time-kill kinetic analysis using bacteria after pre-exposure to clarithromycin, amikacin or tigecycline for 24-hours and we constructed isogenic knockout and knockdown strains. To assess strain specificity, pan-genome analysis of 35 strains from all three subspecies was performed. Mycobacterium abscessus shows both drug-specific and common transcriptomic responses to antibiotic exposure. Ribosome-targeting antibiotics clarithromycin, amikacin and tigecycline elicit a common response characterized by upregulation of ribosome structural genes, the WhiB7 regulon and transferases, accompanied by downregulation of respiration through NuoA-N. Exposure to any of these drugs decreases susceptibility to ribosome-targeting drugs from multiple classes. The cytochrome bd-type quinol oxidase contributes to clofazimine tolerance in M. abscessus and the sigma factor sigH but not anti-sigma factor MAB_3542c is involved in tigecycline resistance. The observed transcriptomic responses are not strain-specific, as all genes involved in tolerance, except erm(41), are found in all included strains.

PMID:34633851 | DOI:10.1128/AAC.01509-21

Genotype data not consistent with clonal transmission of sea turtle fibropapillomatosis or goldfish schwannoma

Fri, 08/10/2021 - 11:00

Wellcome Open Res. 2021 Sep 2;6:219. doi: 10.12688/wellcomeopenres.17073.1. eCollection 2021.

ABSTRACT

Recent discoveries of transmissible cancers in multiple bivalve species suggest that direct transmission of cancer cells within species may be more common than previously thought, particularly in aquatic environments. Fibropapillomatosis occurs with high prevalence in green sea turtles ( Chelonia mydas) and the geographic range of disease has increased since fibropapillomatosis was first reported in this species. Widespread incidence of schwannomas, benign tumours of Schwann cell origin, reported in aquarium-bred goldfish (Carassius auratus), suggest an infectious aetiology. We investigated the hypothesis that cancers in these species arise by clonal transmission of cancer cells. Through analysis of polymorphic microsatellite alleles, we demonstrate concordance of host and tumour genotypes in diseased animals. These results imply that the tumours examined arose from independent oncogenic transformation of host tissue and were not clonally transmitted. Further, failure to experimentally transmit goldfish schwannoma via water exposure or inoculation suggest that this disease is unlikely to have an infectious aetiology.

PMID:34622016 | PMC:PMC8459624 | DOI:10.12688/wellcomeopenres.17073.1

The role of viral genomics in understanding COVID-19 outbreaks in long-term care facilities

Tue, 05/10/2021 - 11:00

Lancet Microbe. 2021 Sep 29. doi: 10.1016/S2666-5247(21)00208-1. Online ahead of print.

ABSTRACT

We reviewed all genomic epidemiology studies on COVID-19 in long-term care facilities (LTCFs) that had been published to date. We found that staff and residents were usually infected with identical, or near identical, SARS-CoV-2 genomes. Outbreaks usually involved one predominant cluster, and the same lineages persisted in LTCFs despite infection control measures. Outbreaks were most commonly due to single or few introductions followed by a spread rather than a series of seeding events from the community into LTCFs. The sequencing of samples taken consecutively from the same individuals at the same facilities showed the persistence of the same genome sequence, indicating that the sequencing technique was robust over time. When combined with local epidemiology, genomics allowed probable transmission sources to be better characterised. The transmission between LTCFs was detected in multiple studies. The mortality rate among residents was high in all facilities, regardless of the lineage. Bioinformatics methods were inadequate in a third of the studies reviewed, and reproducing the analyses was difficult because sequencing data were not available in many facilities.

PMID:34608459 | PMC:PMC8480962 | DOI:10.1016/S2666-5247(21)00208-1

Graph Representation Forecasting of Patient's Medical Conditions: Toward a Digital Twin

Mon, 04/10/2021 - 11:00

Front Genet. 2021 Sep 16;12:652907. doi: 10.3389/fgene.2021.652907. eCollection 2021.

ABSTRACT

Objective: Modern medicine needs to shift from a wait and react, curative discipline to a preventative, interdisciplinary science aiming at providing personalized, systemic, and precise treatment plans to patients. To this purpose, we propose a "digital twin" of patients modeling the human body as a whole and providing a panoramic view over individuals' conditions. Methods: We propose a general framework that composes advanced artificial intelligence (AI) approaches and integrates mathematical modeling in order to provide a panoramic view over current and future pathophysiological conditions. Our modular architecture is based on a graph neural network (GNN) forecasting clinically relevant endpoints (such as blood pressure) and a generative adversarial network (GAN) providing a proof of concept of transcriptomic integrability. Results: We tested our digital twin model on two simulated clinical case studies combining information at organ, tissue, and cellular level. We provided a panoramic overview over current and future patient's conditions by monitoring and forecasting clinically relevant endpoints representing the evolution of patient's vital parameters using the GNN model. We showed how to use the GAN to generate multi-tissue expression data for blood and lung to find associations between cytokines conditioned on the expression of genes in the renin-angiotensin pathway. Our approach was to detect inflammatory cytokines, which are known to have effects on blood pressure and have previously been associated with SARS-CoV-2 infection (e.g., CXCR6, XCL1, and others). Significance: The graph representation of a computational patient has potential to solve important technological challenges in integrating multiscale computational modeling with AI. We believe that this work represents a step forward toward next-generation devices for precision and predictive medicine.

PMID:34603366 | PMC:PMC8481902 | DOI:10.3389/fgene.2021.652907

Serological profile of first SARS-CoV-2 reinfection cases detected within the SIREN study

Sun, 03/10/2021 - 11:00

J Infect. 2021 Sep 30:S0163-4453(21)00489-8. doi: 10.1016/j.jinf.2021.09.019. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the serological profile of first two SARS-CoV-2 confirmed reinfections in the national healthcare worker cohort study SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) and potentially identify correlates of protection against reinfection.

METHODS: In addition to routine testing within the SIREN study, viral culture, sequencing and phylogenetic analysis were performed. Total antibody testing (Anti-SARS-CoV-2 nucleocapsid and Anti-SARS-CoV-2 spike) were complemented by receptor binding domain indirect ELISA and neutralising antibody assays.

RESULTS: The first two SARS-CoV-2 confirmed reinfections had mild symptomatic illness episodes from which infectious virus was recovered at the time of reinfection. The recovered viruses and their sequences were closely related to viruses circulating locally during the time of reinfection and serology was consistent with reinfection. Prior to reinfection, both cases had ELISA and immunoblot detectable anti-N antibodies, but lacked live virus neutralising antibody. Within days following reinfection, neutralising antibodies became detectable and anti-N and anti-S binding antibodies were boosted.

CONCLUSIONS: We hypothesise that titres of neutralising antibody can be used as a correlate of protection against reinfection. Further analysis using a case-control design is essential in order to confirm this hypothesis.

PMID:34600935 | DOI:10.1016/j.jinf.2021.09.019

Species A rotavirus reverse genetics: Achievements and prospects

Sun, 03/10/2021 - 11:00

Virus Res. 2021 Sep 30:198583. doi: 10.1016/j.virusres.2021.198583. Online ahead of print.

NO ABSTRACT

PMID:34600933 | DOI:10.1016/j.virusres.2021.198583

Multivalent poultry vaccine development using Protein Glycan Coupling Technology

Sun, 03/10/2021 - 11:00

Microb Cell Fact. 2021 Oct 2;20(1):193. doi: 10.1186/s12934-021-01682-4.

ABSTRACT

BACKGROUND: Poultry is the world's most popular animal-based food and global production has tripled in the past 20 years alone. Low-cost vaccines that can be combined to protect poultry against multiple infections are a current global imperative. Glycoconjugate vaccines, which consist of an immunogenic protein covalently coupled to glycan antigens of the targeted pathogen, have a proven track record in human vaccinology, but have yet to be used for livestock due to prohibitively high manufacturing costs. To overcome this, we use Protein Glycan Coupling Technology (PGCT), which enables the production of glycoconjugates in bacterial cells at considerably reduced costs, to generate a candidate glycan-based live vaccine intended to simultaneously protect against Campylobacter jejuni, avian pathogenic Escherichia coli (APEC) and Clostridium perfringens. Campylobacter is the most common cause of food poisoning, whereas colibacillosis and necrotic enteritis are widespread and devastating infectious diseases in poultry.

RESULTS: We demonstrate the functional transfer of C. jejuni protein glycosylation (pgl) locus into the genome of APEC χ7122 serotype O78:H9. The integration caused mild attenuation of the χ7122 strain following oral inoculation of chickens without impairing its ability to colonise the respiratory tract. We exploit the χ7122 pgl integrant as bacterial vectors delivering a glycoprotein decorated with the C. jejuni heptasaccharide glycan antigen. To this end we engineered χ7122 pgl to express glycosylated NetB toxoid from C. perfringens and tested its ability to reduce caecal colonisation of chickens by C. jejuni and protect against intra-air sac challenge with the homologous APEC strain.

CONCLUSIONS: We generated a candidate glycan-based multivalent live vaccine with the potential to induce protection against key avian and zoonotic pathogens (C. jejuni, APEC, C. perfringens). The live vaccine failed to significantly reduce Campylobacter colonisation under the conditions tested but was protective against homologous APEC challenge. Nevertheless, we present a strategy towards the production of low-cost "live-attenuated multivalent vaccine factories" with the ability to express glycoconjugates in poultry.

PMID:34600535 | DOI:10.1186/s12934-021-01682-4

Thermally Driven Membrane Phase Transitions Enable Content Reshuffling in Primitive Cells

Fri, 01/10/2021 - 11:00

J Am Chem Soc. 2021 Oct 1. doi: 10.1021/jacs.1c06595. Online ahead of print.

ABSTRACT

Self-assembling single-chain amphiphiles available in the prebiotic environment likely played a fundamental role in the advent of primitive cell cycles. However, the instability of prebiotic fatty acid-based membranes to temperature and pH seems to suggest that primitive cells could only host prebiotically relevant processes in a narrow range of nonfluctuating environmental conditions. Here we propose that membrane phase transitions, driven by environmental fluctuations, enabled the generation of daughter protocells with reshuffled content. A reversible membrane-to-oil phase transition accounts for the dissolution of fatty acid-based vesicles at high temperatures and the concomitant release of protocellular content. At low temperatures, fatty acid bilayers reassemble and encapsulate reshuffled material in a new cohort of protocells. Notably, we find that our disassembly/reassembly cycle drives the emergence of functional RNA-containing primitive cells from parent nonfunctional compartments. Thus, by exploiting the intrinsic instability of prebiotic fatty acid vesicles, our results point at an environmentally driven tunable prebiotic process, which supports the release and reshuffling of oligonucleotides and membrane components, potentially leading to a new generation of protocells with superior traits. In the absence of protocellular transport machinery, the environmentally driven disassembly/assembly cycle proposed herein would have plausibly supported protocellular content reshuffling transmitted to primitive cell progeny, hinting at a potential mechanism important to initiate Darwinian evolution of early life forms.

PMID:34597506 | DOI:10.1021/jacs.1c06595

Optimizing noninvasive sampling of a zoonotic bat virus

Fri, 01/10/2021 - 11:00

Ecol Evol. 2021 Aug 27;11(18):12307-12321. doi: 10.1002/ece3.7830. eCollection 2021 Sep.

ABSTRACT

Outbreaks of infectious viruses resulting from spillover events from bats have brought much attention to bat-borne zoonoses, which has motivated increased ecological and epidemiological studies on bat populations. Field sampling methods often collect pooled samples of bat excreta from plastic sheets placed under-roosts. However, positive bias is introduced because multiple individuals may contribute to pooled samples, making studies of viral dynamics difficult. Here, we explore the general issue of bias in spatial sample pooling using Hendra virus in Australian bats as a case study. We assessed the accuracy of different under-roost sampling designs using generalized additive models and field data from individually captured bats and pooled urine samples. We then used theoretical simulation models of bat density and under-roost sampling to understand the mechanistic drivers of bias. The most commonly used sampling design estimated viral prevalence 3.2 times higher than individual-level data, with positive bias 5-7 times higher than other designs due to spatial autocorrelation among sampling sheets and clustering of bats in roosts. Simulation results indicate using a stratified random design to collect 30-40 pooled urine samples from 80 to 100 sheets, each with an area of 0.75-1 m2, and would allow estimation of true prevalence with minimum sampling bias and false negatives. These results show that widely used under-roost sampling techniques are highly sensitive to viral presence, but lack specificity, providing limited information regarding viral dynamics. Improved estimation of true prevalence can be attained with minor changes to existing designs such as reducing sheet size, increasing sheet number, and spreading sheets out within the roost area. Our findings provide insight into how spatial sample pooling is vulnerable to bias for a wide range of systems in disease ecology, where optimal sampling design is influenced by pathogen prevalence, host population density, and patterns of aggregation.

PMID:34594501 | PMC:PMC8462156 | DOI:10.1002/ece3.7830

A prenylated dsRNA sensor protects against severe COVID-19

Tue, 28/09/2021 - 11:00

Science. 2021 Sep 28:eabj3624. doi: 10.1126/science.abj3624. Online ahead of print.

ABSTRACT

[Figure: see text].

PMID:34581622 | DOI:10.1126/science.abj3624

EAP45 association with budding HIV-1; kinetics and domain requirements

Tue, 28/09/2021 - 11:00

Traffic. 2021 Sep 27. doi: 10.1111/tra.12820. Online ahead of print.

ABSTRACT

A number of viruses including HIV use the ESCRT system to bud from the infected cell. We have previously confirmed biochemically that ESCRT-II is involved in this process in HIV-1 and have defined the molecular domains that are important for this. Here, using SNAP-tag fluorescent labelling and both fixed and live cell imaging we show that the ESCRT-II component EAP45 colocalises with the HIV protein Gag at the plasma membrane in a temporal and quantitative manner, similar to that previously shown for ALIX and Gag. We show evidence that a proportion of EAP45 may be packaged within virions, and we confirm the importance of the N terminus of EAP45 and specifically the H0 domain in this process. By contrast, the Glue domain of EAP45 is more critical for recruitment during cytokinesis, emphasising that viruses have ways of recruiting cellular components that may be distinct from those used by some cellular processes. This raises the prospect of selective interference with the pathway to inhibit viral function while leaving cellular functions relatively unperturbed. This article is protected by copyright. All rights reserved.

PMID:34580994 | DOI:10.1111/tra.12820

A role for arthropods as vectors of multidrug-resistant Enterobacterales in surgical site infections from South Asia

Tue, 28/09/2021 - 11:00

Nat Microbiol. 2021 Sep 27. doi: 10.1038/s41564-021-00965-1. Online ahead of print.

ABSTRACT

Understanding how multidrug-resistant Enterobacterales (MDRE) are transmitted in low- and middle-income countries (LMICs) is critical for implementing robust policies to curb the increasing burden of antimicrobial resistance (AMR). Here, we analysed samples from surgical site infections (SSIs), hospital surfaces (HSs) and arthropods (summer and winter 2016) to investigate the incidence and transmission of MDRE in a public hospital in Pakistan. We investigated Enterobacterales containing resistance genes (blaCTX-M-15, blaNDM and blaOXA-48-like) for identification, antimicrobial susceptibility testing and whole-genome sequencing. Genotypes, phylogenetic relationships and transmission events for isolates from different sources were investigated using single-nucleotide polymorphism (SNP) analysis with a cut-off of ≤20 SNPs. Escherichia coli (14.3%), Klebsiella pneumoniae (10.9%) and Enterobacter cloacae (16.3%) were the main MDRE species isolated. The carbapenemase gene blaNDM was most commonly detected, with 15.5%, 15.1% and 13.3% of samples positive in SSIs, HSs and arthropods, respectively. SNP (≤20) and spatiotemporal analysis revealed linkages in bacteria between SSIs, HSs and arthropods supporting the One Health approach to underpin infection control policies across LMICs and control AMR.

PMID:34580444 | DOI:10.1038/s41564-021-00965-1

Commentary on the use of the reproduction number <em>R</em> during the COVID-19 pandemic

Mon, 27/09/2021 - 11:00

Stat Methods Med Res. 2021 Sep 27:9622802211037079. doi: 10.1177/09622802211037079. Online ahead of print.

ABSTRACT

Since the beginning of the COVID-19 pandemic, the reproduction number R has become a popular epidemiological metric used to communicate the state of the epidemic. At its most basic, R is defined as the average number of secondary infections caused by one primary infected individual. R seems convenient, because the epidemic is expanding if R>1 and contracting if R<1. The magnitude of R indicates by how much transmission needs to be reduced to control the epidemic. Using R in a naïve way can cause new problems. The reasons for this are threefold: (1) There is not just one definition of R but many, and the precise definition of R affects both its estimated value and how it should be interpreted. (2) Even with a particular clearly defined R, there may be different statistical methods used to estimate its value, and the choice of method will affect the estimate. (3) The availability and type of data used to estimate R vary, and it is not always clear what data should be included in the estimation. In this review, we discuss when R is useful, when it may be of use but needs to be interpreted with care, and when it may be an inappropriate indicator of the progress of the epidemic. We also argue that careful definition of R, and the data and methods used to estimate it, can make R a more useful metric for future management of the epidemic.

PMID:34569883 | DOI:10.1177/09622802211037079

VGEA: an RNA viral assembly toolkit

Mon, 27/09/2021 - 11:00

PeerJ. 2021 Sep 6;9:e12129. doi: 10.7717/peerj.12129. eCollection 2021.

ABSTRACT

Next generation sequencing (NGS)-based studies have vastly increased our understanding of viral diversity. Viral sequence data obtained from NGS experiments are a rich source of information, these data can be used to study their epidemiology, evolution, transmission patterns, and can also inform drug and vaccine design. Viral genomes, however, represent a great challenge to bioinformatics due to their high mutation rate and forming quasispecies in the same infected host, bringing about the need to implement advanced bioinformatics tools to assemble consensus genomes well-representative of the viral population circulating in individual patients. Many tools have been developed to preprocess sequencing reads, carry-out de novo or reference-assisted assembly of viral genomes and assess the quality of the genomes obtained. Most of these tools however exist as standalone workflows and usually require huge computational resources. Here we present (Viral Genomes Easily Analyzed), a Snakemake workflow for analyzing RNA viral genomes. VGEA enables users to map sequencing reads to the human genome to remove human contaminants, split bam files into forward and reverse reads, carry out de novo assembly of forward and reverse reads to generate contigs, pre-process reads for quality and contamination, map reads to a reference tailored to the sample using corrected contigs supplemented by the user's choice of reference sequences and evaluate/compare genome assemblies. We designed a project with the aim of creating a flexible, easy-to-use and all-in-one pipeline from existing/stand-alone bioinformatics tools for viral genome analysis that can be deployed on a personal computer. VGEA was built on the Snakemake workflow management system and utilizes existing tools for each step: fastp (Chen et al., 2018) for read trimming and read-level quality control, BWA (Li & Durbin, 2009) for mapping sequencing reads to the human reference genome, SAMtools (Li et al., 2009) for extracting unmapped reads and also for splitting bam files into fastq files, IVA (Hunt et al., 2015) for de novo assembly to generate contigs, shiver (Wymant et al., 2018) to pre-process reads for quality and contamination, then map to a reference tailored to the sample using corrected contigs supplemented with the user's choice of existing reference sequences, SeqKit (Shen et al., 2016) for cleaning shiver assembly for QUAST, QUAST (Gurevich et al., 2013) to evaluate/assess the quality of genome assemblies and MultiQC (Ewels et al., 2016) for aggregation of the results from fastp, BWA and QUAST. Our pipeline was successfully tested and validated with SARS-CoV-2 (n = 20), HIV-1 (n = 20) and Lassa Virus (n = 20) datasets all of which have been made publicly available. VGEA is freely available on GitHub at: https://github.com/pauloluniyi/VGEA under the GNU General Public License.

PMID:34567846 | PMC:PMC8428259 | DOI:10.7717/peerj.12129

What can mechanistic models tell us about guard cells, photosynthesis, and water use efficiency?

Mon, 27/09/2021 - 11:00

Trends Plant Sci. 2021 Sep 23:S1360-1385(21)00241-7. doi: 10.1016/j.tplants.2021.08.010. Online ahead of print.

ABSTRACT

Stomatal pores facilitate gaseous exchange between the inner air spaces of the leaf and the atmosphere. The pores open to enable CO2 entry for photosynthesis and close to reduce transpirational water loss. How stomata respond to the environment has long attracted interest in modeling as a tool to understand the consequences for the plant and for the ecosystem. Models that focus on stomatal conductance for gas exchange make intuitive sense, but such models need also to connect with the mechanics of the guard cells that regulate pore aperture if we are to understand the 'decisions made' by stomata, their impacts on the plant and on the global environment.

PMID:34565672 | DOI:10.1016/j.tplants.2021.08.010

An <em>in vitro</em> model for the cultivation of polymicrobial biofilms under continuous-flow conditions

Fri, 24/09/2021 - 11:00

F1000Res. 2021 Aug 13;10:801. doi: 10.12688/f1000research.55140.1. eCollection 2021.

ABSTRACT

The airways of people with cystic fibrosis (CF) are often chronically colonised with a diverse array of bacterial and fungal species. However, little is known about the relative partitioning of species between the planktonic and biofilm modes of growth in the airways. Existing in vivo and in vitro models of CF airway infection are ill-suited for the long-term recapitulation of mixed microbial communities. Here we describe a simple, in vitro continuous-flow model for the cultivation of polymicrobial biofilms and planktonic cultures on different substrata. Our data provide evidence for inter-species antagonism and synergism in biofilm ecology. We further show that the type of substratum on which the biofilms grow has a profound influence on their species composition. This happens without any major alteration in the composition of the surrounding steady-state planktonic community. Our experimentally-tractable model enables the systematic study of planktonic and biofilm communities under conditions that are nutritionally reminiscent of the CF airway microenvironment, something not possible using any existing in vivo models of CF airway infection.

PMID:34557293 | PMC:PMC8442117 | DOI:10.12688/f1000research.55140.1