scholarly journals Paratype: A genotyping framework and an open-source tool for Salmonella Paratyphi A

2021 ◽  
Author(s):  
Arif M. Tanmoy ◽  
Yogesh Hooda ◽  
Mohammasd S. I. Sajib ◽  
Kesia E. da Silva ◽  
Junaid Iqbal ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Large Scale ◽  
Vaccine Development ◽  
Global Analysis ◽  
Treatment Strategies ◽  
Genomic Analysis ◽  
Genomic Variation ◽  
Global Database ◽  
Command Line Tool ◽  
Conserved Gene

Background: Salmonella enterica serovar Paratyphi A (Salmonella Paratyphi A) is the primary causative agent of paratyphoid fever, which is responsible for an estimated 3.4 million infections annually. However, little genomic information is available on population structure, antimicrobial resistance (AMR), and spatiotemporal distribution of the pathogen. With rising antimicrobial resistance and no licensed vaccines, genomic surveillance is important to track the evolution of this pathogen and monitor transmission. Results: We performed whole-genome sequencing of 817 Salmonella Paratyphi A isolates collected from Bangladesh, Nepal, and Pakistan and added publicly available 562 genomes to build a global database representing 37 countries, covering 1917-2019. To track the evolution of Salmonella Paratyphi A, we used the existing lineage scheme, developed earlier based on a small dataset, but certain sub-lineages were not homologous, and many isolates could not be assigned a lineage. Therefore, we developed a single nucleotide polymorphism based genotyping scheme, Paratype, a tool that segregates Salmonella Paratyphi A into three primary and nine secondary clades, and 18 genotypes. Each genotype has been assigned a unique allele definition located on a conserved gene. Using Paratype, we identified genomic variation between different sampling locations and specific AMR markers, and mutations in the O2-polysaccharide synthesis locus, a candidate for vaccine development. Conclusions: This large-scale global analysis proposes the first genotyping tool for Salmonella Paratyphi A. Paratype has already been released (https://github.com/CHRF-Genomics/Paratype) as an open-access, command-line tool and is being adopted for large scale genomic analysis. This tool will assist future genomic surveillance and help inform prevention and treatment strategies.

scholarly journals Local Evolutionary Patterns of Human Respiratory Syncytial Virus Derived from Whole-Genome Sequencing

2015 ◽  
Vol 89 (7) ◽  
pp. 3444-3454 ◽  
Author(s):  
Charles N. Agoti ◽  
James R. Otieno ◽  
Patrick K. Munywoki ◽  
Alexander G. Mwihuri ◽  
Patricia A. Cane ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Large Scale ◽  
Vaccine Development ◽  
Human Respiratory Syncytial Virus ◽  
Genomic Variation ◽  
Genomic Sequences ◽  
The Novel ◽  
Sequencing Method ◽  
The World ◽  
Syncytial Virus

ABSTRACTHuman respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies.IMPORTANCEThe new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment.

scholarly journals Prediction of Burkholderia pseudomallei DsbA substrates identifies potential virulence factors and vaccine targets

2020 ◽  
Author(s):  
Ben Vezina ◽  
Guillaume A. Petit ◽  
Jennifer L. Martin ◽  
Maria A. Halili
Keyword(s):  
Drug Discovery ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Burkholderia Pseudomallei ◽  
Large Scale ◽  
Vaccine Development ◽  
Protein A ◽  
Genomic Analysis ◽  
Disease Pathogenesis ◽  
Gram Negative

AbstractIdentification of bacterial virulence factors is critical for understanding disease pathogenesis, drug discovery and vaccine development. In this study we used two approaches to predict virulence factors of Burkholderia pseudomallei, the Gram-negative bacterium that causes melioidosis. B. pseudomallei is naturally antibiotic resistant and there are no melioidosis vaccines. To identify B. pseudomallei protein targets for drug discovery and vaccine development, we chose to search for substrates of the B. pseudomallei periplasmic disulfide bond forming protein A (DsbA). DsbA introduces disulfide bonds into extra-cytoplasmic proteins and is essential for virulence in many Gram-negative organism, including B. pseudomallei. The first approach to identify B. pseudomallei DsbA virulence factor substrates was a large-scale genomic analysis of 511 unique B. pseudomallei disease-associated strains. This yielded 4,496 core gene products, of which we hypothesise 263 are DsbA substrates. Manual curation of the 263 mature proteins yielded 73 associated with disease pathogenesis or virulence. These were screened for structural homologues to predict potential B-cell epitopes. In the second approach, we searched the B. pseudomallei genome for homologues of the more than 90 known DsbA substrates in other bacteria. Using this approach, we identified 15 potential B. pseudomallei DsbA virulence factor substrates. Two putative B. pseudomallei virulence factors were identified by both methods: homologues of PenI family β-lactamase and of succinate dehydrogenase flavoprotein subunit. These two proteins could serve as high priority targets for future B. pseudomallei virulence factor characterization.

scholarly journals Global population genomic analysis of Mycoplasma bovis isolates reveals transcontinental variations and potential virulence genes

2020 ◽  
Author(s):  
Roshan Kumar ◽  
Karen Register ◽  
Jane Christopher-Hennings ◽  
Paolo Moroni ◽  
Gloria Gioa ◽  
...  
Keyword(s):  
Population Structure ◽  
North America ◽  
Large Scale ◽  
Vaccine Development ◽  
Population Analysis ◽  
Genomic Analysis ◽  
Control Measures ◽  
Mycoplasma Bovis ◽  
Whole Genome ◽  
Host Association

AbstractAmong more than twenty species belonging to the class Mollecutes, Mycoplasma bovis is the most common cause of bovine mycoplasmosis in North America and Europe. Bovine mycoplasmosis causes significant economic loss in the cattle industry. The number of M. bovis positive herds has recently increased in North America and Europe. Since antibiotic treatment is ineffective and no efficient vaccine is available, M. bovis-induced mycoplasmosis is primarily controlled by herd management measures such as the restriction of moving infected animals out of the herds and culling of infected animals or shedders. To better understand the population structure and genomic factors that may contribute to its transmission, we sequenced 147 M. bovis strains isolated from four different countries and hosts, primarily cattle. We performed a large-scale comparative analysis of M. bovis genomes by integrating 104 publicly available genomes and our dataset (251 total genomes). A whole genome-single nucleotide polymorphism (SNP)-based phylogeny revealed that M. bovis population structure is composed of five clades with one of the isolates clustering with the outgroup M. agalactiae. These isolates were found to cluster with those from Canada, Israel, Lithuania, and Switzerland, suggesting trans-continental transmission of the strains. We also validated a previous report suggesting minimum divergence in isolates of Australian origin, which grouped within a single clade along with strains from China and Israel. However, no observable pattern of host association in M. bovis genomes was found in this study. Our comparative genome analysis also revealed that M. bovis has an open pangenome with a large breadth of unexplored diversity of genes. Analysis of vsp gene-host association revealed a single vsp significantly associated with bovine isolates that may be targeted for diagnostics or vaccine development. Our study also found that M. bovis genome harbors a large number of IS elements, including a novel 1624 bp IS element, and ISMbov9. Collectively, the genome data and the whole genome-based population analysis in this study may help to develop control measures to reduce the incidence of M. bovis-induced mycoplasmosis in cattle and/or to identify candidate genes for vaccine development.

scholarly journals Prediction of Burkholderia pseudomallei DsbA substrates identifies potential virulence factors and vaccine targets

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241306
Author(s):  
Ben Vezina ◽  
Guillaume A. Petit ◽  
Jennifer L. Martin ◽  
Maria A. Halili
Keyword(s):  
Drug Discovery ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Burkholderia Pseudomallei ◽  
Large Scale ◽  
Vaccine Development ◽  
Protein A ◽  
Genomic Analysis ◽  
Disease Pathogenesis ◽  
Gram Negative

Identification of bacterial virulence factors is critical for understanding disease pathogenesis, drug discovery and vaccine development. In this study we used two approaches to predict virulence factors of Burkholderia pseudomallei, the Gram-negative bacterium that causes melioidosis. B. pseudomallei is naturally antibiotic resistant and there are no clinically available melioidosis vaccines. To identify B. pseudomallei protein targets for drug discovery and vaccine development, we chose to search for substrates of the B. pseudomallei periplasmic disulfide bond forming protein A (DsbA). DsbA introduces disulfide bonds into extra-cytoplasmic proteins and is essential for virulence in many Gram-negative organism, including B. pseudomallei. The first approach to identify B. pseudomallei DsbA virulence factor substrates was a large-scale genomic analysis of 511 unique B. pseudomallei disease-associated strains. This yielded 4,496 core gene products, of which we hypothesise 263 are DsbA substrates. Manual curation and database screening of the 263 mature proteins yielded 81 associated with disease pathogenesis or virulence. These were screened for structural homologues to predict potential B-cell epitopes. In the second approach, we searched the B. pseudomallei genome for homologues of the more than 90 known DsbA substrates in other bacteria. Using this approach, we identified 15 putative B. pseudomallei DsbA virulence factor substrates, with two of these previously identified in the genomic approach, bringing the total number of putative DsbA virulence factor substrates to 94. The two putative B. pseudomallei virulence factors identified by both methods are homologues of PenI family β-lactamase and a molecular chaperone. These two proteins could serve as high priority targets for future B. pseudomallei virulence factor characterization.

scholarly journals Large-scale genomic analysis of antimicrobial resistance in the zoonotic pathogen Streptococcus suis

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Nazreen F. Hadjirin ◽  
Eric L. Miller ◽  
Gemma G. R. Murray ◽  
Phung L. K. Yen ◽  
Ho D. Phuc ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Large Scale ◽  
Genomic Analysis ◽  
Streptococcus Suis ◽  
Multidrug Resistant ◽  
Beta Lactam ◽  
Contributing Factors ◽  
Usage Patterns ◽  
Natural Separation ◽  
Serious Disease

Abstract Background Antimicrobial resistance (AMR) is among the gravest threats to human health and food security worldwide. The use of antimicrobials in livestock production can lead to emergence of AMR, which can have direct effects on humans through spread of zoonotic disease. Pigs pose a particular risk as they are a source of zoonotic diseases and receive more antimicrobials than most other livestock. Here we use a large-scale genomic approach to characterise AMR in Streptococcus suis, a commensal found in most pigs, but which can also cause serious disease in both pigs and humans. Results We obtained replicated measures of Minimum Inhibitory Concentration (MIC) for 16 antibiotics, across a panel of 678 isolates, from the major pig-producing regions of the world. For several drugs, there was no natural separation into ‘resistant’ and ‘susceptible’, highlighting the need to treat MIC as a quantitative trait. We found differences in MICs between countries, consistent with their patterns of antimicrobial usage. AMR levels were high even for drugs not used to treat S. suis, with many multidrug-resistant isolates. Similar levels of resistance were found in pigs and humans from regions associated with zoonotic transmission. We next used whole genome sequences for each isolate to identify 43 candidate resistance determinants, 22 of which were novel in S. suis. The presence of these determinants explained most of the variation in MIC. But there were also interesting complications, including epistatic interactions, where known resistance alleles had no effect in some genetic backgrounds. Beta-lactam resistance involved many core genome variants of small effect, appearing in a characteristic order. Conclusions We present a large dataset allowing the analysis of the multiple contributing factors to AMR in S. suis. The high levels of AMR in S. suis that we observe are reflected by antibiotic usage patterns but our results confirm the potential for genomic data to aid in the fight against AMR.

scholarly journals Salmonella in Captive Reptiles and Their Environment—Can We Tame the Dragon?

2021 ◽  
Vol 9 (5) ◽  
pp. 1012
Author(s):  
Magdalena Zając ◽  
Magdalena Skarżyńska ◽  
Anna Lalak ◽  
Renata Kwit ◽  
Aleksandra Śmiałowska-Węglińska ◽  
...  
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Detection Rate ◽  
Large Scale ◽  
Isolation And Identification ◽  
Epidemiological Analysis ◽  
High Occurrence ◽  
Salmonella Serovars ◽  
Floor Surfaces

Reptiles are considered a reservoir of a variety of Salmonella (S.) serovars. Nevertheless, due to a lack of large-scale research, the importance of Reptilia as a Salmonella vector still remains not completely recognized. A total of 731 samples collected from reptiles and their environment were tested. The aim of the study was to assess the prevalence of Salmonella in exotic reptiles kept in Poland and to confirm Salmonella contamination of the environment after reptile exhibitions. The study included Salmonella isolation and identification, followed by epidemiological analysis of the antimicrobial resistance of the isolates. Implementation of a pathway additional to the standard Salmonella isolation protocol led to a 21% increase in the Salmonella serovars detection rate. The study showed a high occurrence of Salmonella, being the highest at 92.2% in snakes, followed by lizards (83.7%) and turtles (60.0%). The pathogen was also found in 81.2% of swabs taken from table and floor surfaces after reptile exhibitions and in two out of three egg samples. A total of 918 Salmonella strains belonging to 207 serovars and serological variants were obtained. We have noted the serovars considered important with respect to public health, i.e., S. Enteritidis, S. Typhimurium, and S. Kentucky. The study proves that exotic reptiles in Poland are a relevant reservoir of Salmonella.

scholarly journals mRNA-Based Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 390
Author(s):  
Frank Kowalzik ◽  
Daniel Schreiner ◽  
Christian Jensen ◽  
Daniel Teschner ◽  
Stephan Gehring ◽  
...  
Keyword(s):  
Large Scale ◽  
New Technologies ◽  
Vaccine Development ◽  
Effective Means ◽  
Cost Effective ◽  
Clinical Applications ◽  
Cell Mediated Immunity ◽  
Healthy Individuals ◽  
Emerging Pathogens ◽  
Cell Genome

Increases in the world’s population and population density promote the spread of emerging pathogens. Vaccines are the most cost-effective means of preventing this spread. Traditional methods used to identify and produce new vaccines are not adequate, in most instances, to ensure global protection. New technologies are urgently needed to expedite large scale vaccine development. mRNA-based vaccines promise to meet this need. mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they (1) involve neither infectious elements nor a risk of stable integration into the host cell genome; (2) generate humoral and cell-mediated immunity; (3) are well-tolerated by healthy individuals; and (4) are less expensive and produced more rapidly by processes that are readily standardized and scaled-up, improving responsiveness to large emerging outbreaks. Multiple mRNA vaccine platforms have demonstrated efficacy in preventing infectious diseases and treating several types of cancers in humans as well as animal models. This review describes the factors that contribute to maximizing the production of effective mRNA vaccine transcripts and delivery systems, and the clinical applications are discussed in detail.

scholarly journals SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nikolaos C. Kyriakidis ◽  
Andrés López-Cortés ◽  
Eduardo Vásconez González ◽  
Alejandra Barreto Grimaldos ◽  
Esteban Ortiz Prado
Keyword(s):  
Neutralizing Antibodies ◽  
Large Scale ◽  
Vaccine Development ◽  
Rna Virus ◽  
Protein S ◽  
Effective Vaccine ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Advantages And Disadvantages ◽  
The World

AbstractThe new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

scholarly journals Systematic Detection of Large-Scale Multi-Gene Horizontal Transfer in Prokaryotes

2021 ◽  
Author(s):  
Lina Kloub ◽  
Sean Gosselin ◽  
Matthew Fullmer ◽  
Joerg Graf ◽  
J Peter Gogarten ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Large Scale ◽  
Single Gene ◽  
Gene Families ◽  
Microbial Evolution ◽  
Phylogenetic Distance ◽  
Secretion Systems ◽  
Type Iii Secretion Systems ◽  
A Genome ◽  
Conserved Gene

Abstract Horizontal gene transfer (HGT) is central to prokaryotic evolution. However, little is known about the “scale” of individual HGT events. In this work, we introduce the first computational framework to help answer the following fundamental question: How often does more than one gene get horizontally transferred in a single HGT event? Our method, called HoMer, uses phylogenetic reconciliation to infer single-gene HGT events across a given set of species/strains, employs several techniques to account for inference error and uncertainty, combines that information with gene order information from extant genomes, and uses statistical analysis to identify candidate horizontal multi-gene transfers (HMGTs) in both extant and ancestral species/strains. HoMer is highly scalable and can be easily used to infer HMGTs across hundreds of genomes. We apply HoMer to a genome-scale dataset of over 22000 gene families from 103 Aeromonas genomes and identify a large number of plausible HMGTs of various scales at both small and large phylogenetic distances. Analysis of these HMGTs reveals interesting relationships between gene function, phylogenetic distance, and frequency of multi-gene transfer. Among other insights, we find that (i) the observed relative frequency of HMGT increases as divergence between genomes increases, (ii) HMGTs often have conserved gene functions, and (iii) rare genes are frequently acquired through HMGT. We also analyze in detail HMGTs involving the zonula occludens toxin and type III secretion systems. By enabling the systematic inference of HMGTs on a large scale, HoMer will facilitate a more accurate and more complete understanding of HGT and microbial evolution.

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