scholarly journals A Comparative Genomic Analysis of Diverse Clonal Types of EnterotoxigenicEscherichia coliReveals Pathovar-Specific Conservation

2010 ◽  
Vol 79 (2) ◽  
pp. 950-960 ◽  
Author(s):  
Jason W. Sahl ◽  
Hans Steinsland ◽  
Julia C. Redman ◽  
Samuel V. Angiuoli ◽  
James P. Nataro ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Genomic Sequence ◽  
Genomic Analysis ◽  
Genomic Diversity ◽  
Comparative Genomic ◽  
Middle Income ◽  
E Coli ◽  
Colonization Factor ◽  
Genomic Core ◽  
Genomic Regions

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) is a major cause of diarrheal illness in children less than 5 years of age in low- and middle-income nations, whereas it is an emerging enteric pathogen in industrialized nations. Despite being an important cause of diarrhea, little is known about the genomic composition of ETEC. To address this, we sequenced the genomes of five ETEC isolates obtained from children in Guinea-Bissau with diarrhea. These five isolates represent distinct and globally dominant ETEC clonal groups. Comparative genomic analyses utilizing a gene-independent whole-genome alignment method demonstrated that sequenced ETEC strains share approximately 2.7 million bases of genomic sequence. Phylogenetic analysis of this “core genome” confirmed the diverse history of the ETEC pathovar and provides a finer resolution of theE. colirelationships than multilocus sequence typing. No identified genomic regions were conserved exclusively in all ETEC genomes; however, we identified more genomic content conserved among ETEC genomes than among non-ETECE. coligenomes, suggesting that ETEC isolates share a genomic core. Comparisons of known virulence and of surface-exposed and colonization factor genes across all sequenced ETEC genomes not only identified variability but also indicated that some antigens are restricted to the ETEC pathovar. Overall, the generation of these five genome sequences, in addition to the two previously generated ETEC genomes, highlights the genomic diversity of ETEC. These studies increase our understanding of ETEC evolution, as well as provide insight into virulence factors and conserved proteins, which may be targets for vaccine development.

scholarly journals Contribution of noncanonical antigens to virulence and adaptive immunity in human infection with enterotoxigenic E. coli

2020 ◽  
Author(s):  
FM Kuhlmann ◽  
RO Laine ◽  
S Afrin ◽  
R Nakajima ◽  
M Akhtar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Human Infection ◽  
Middle Income ◽  
Symptomatic Disease ◽  
E Coli ◽  
Middle Income Countries ◽  
Colonization Factor ◽  
Specific Antigens ◽  
Colonization Factors

AbstractEnterotoxigenic E. coli (ETEC) contribute significantly to the substantial burden of infectious diarrhea among children living in low and middle income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as non-diarrheal sequelae related to these infections including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches focused on a subset of antigens known as colonization factors (CFs). To identify additional conserved immunogens, we mined genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n=118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n=52), and toxin subunits to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this open-aperture approach, we found that immune responses were largely constrained to a small number of antigens including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children < 2 years of age, both EtpA and a second noncanonical antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for more recently discovered noncanonical antigens in virulence and the development of adaptive immune responses during ETEC infections, findings that may inform vaccine design efforts to complement existing approaches.

scholarly journals The Pangenome Structure of Escherichia coli: Comparative Genomic Analysis of E. coli Commensal and Pathogenic Isolates

2008 ◽  
Vol 190 (20) ◽  
pp. 6881-6893 ◽  
Author(s):  
David A. Rasko ◽  
M. J. Rosovitz ◽  
Garry S. A. Myers ◽  
Emmanuel F. Mongodin ◽  
W. Florian Fricke ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Genome Sequencing ◽  
Genomic Analysis ◽  
Comparative Genomic Analysis ◽  
Genomic Diversity ◽  
Comparative Genomic ◽  
Whole Genome ◽  
E Coli ◽  
Important Group ◽  
Commensal Species

ABSTRACT Whole-genome sequencing has been skewed toward bacterial pathogens as a consequence of the prioritization of medical and veterinary diseases. However, it is becoming clear that in order to accurately measure genetic variation within and between pathogenic groups, multiple isolates, as well as commensal species, must be sequenced. This study examined the pangenomic content of Escherichia coli. Six distinct E. coli pathovars can be distinguished using molecular or phenotypic markers, but only two of the six pathovars have been subjected to any genome sequencing previously. Thus, this report provides a seminal description of the genomic contents and unique features of three unsequenced pathovars, enterotoxigenic E. coli, enteropathogenic E. coli, and enteroaggregative E. coli. We also determined the first genome sequence of a human commensal E. coli isolate, E. coli HS, which will undoubtedly provide a new baseline from which workers can examine the evolution of pathogenic E. coli. Comparison of 17 E. coli genomes, 8 of which are new, resulted in identification of ∼2,200 genes conserved in all isolates. We were also able to identify genes that were isolate and pathovar specific. Fewer pathovar-specific genes were identified than anticipated, suggesting that each isolate may have independently developed virulence capabilities. Pangenome calculations indicate that E. coli genomic diversity represents an open pangenome model containing a reservoir of more than 13,000 genes, many of which may be uncharacterized but important virulence factors. This comparative study of the species E. coli, while descriptive, should provide the basis for future functional work on this important group of pathogens.

scholarly journals Comparative genomic analysis of Mycobacterium intracellulare: implications for clinical taxonomic classification in pulmonary Mycobacterium avium-intracellulare complex disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yoshitaka Tateishi ◽  
Yuriko Ozeki ◽  
Akihito Nishiyama ◽  
Mari Miki ◽  
Ryoji Maekura ◽  
...  
Keyword(s):  
Complex Disease ◽  
Genomic Analysis ◽  
Comparative Genomic Analysis ◽  
Genomic Diversity ◽  
Comparative Genomic ◽  
Mycobacterium Intracellulare ◽  
Clinical Strains ◽  
Genetic Components ◽  
Genomic Regions ◽  
Insight Into

Abstract Background Mycobacterium intracellulare is a representative etiological agent of emerging pulmonary M. avium-intracellulare complex disease in the industrialized countries worldwide. The recent genome sequencing of clinical strains isolated from pulmonary M. avium-intracellulare complex disease has provided insight into the genomic characteristics of pathogenic mycobacteria, especially for M. avium; however, the genomic characteristics of M. intracellulare remain to be elucidated. Results In this study, we performed comparative genomic analysis of 55 M. intracellulare and related strains such as M. paraintracellulare (MP), M. indicus pranii (MIP) and M. yonogonense. Based on the average nucleotide identity, the clinical M. intracellulare strains were phylogenetically grouped in two clusters: (1) the typical M. intracellulare (TMI) group, including ATCC13950 and virulent M.i.27 and M.i.198 that we previously reported, and (2) the MP-MIP group. The alignment of the genomic regions was mostly preserved between groups. Plasmids were identified between groups and subgroups, including a plasmid common among some strains of the M.i.27 subgroup. Several genomic regions including those encoding factors involved in lipid metabolism (e.g., fadE3, fadE33), transporters (e.g., mce3), and type VII secretion system (genes of ESX-2 system) were shown to be hypermutated in the clinical strains. M. intracellulare was shown to be pan-genomic at the species and subspecies levels. The mce genes were specific to particular subspecies, suggesting that these genes may be helpful in discriminating virulence phenotypes between subspecies. Conclusions Our data suggest that genomic diversity among M. intracellulare, M. paraintracellulare, M. indicus pranii and M. yonogonense remains at the subspecies or genovar levels and does not reach the species level. Genetic components such as mce genes revealed by the comparative genomic analysis could be the novel focus for further insight into the mechanism of human pathogenesis for M. intracellulare and related strains.

scholarly journals Contribution of noncanonical antigens to virulence and adaptive immunity in human infection with enterotoxigenic E. coli

2021 ◽  
Author(s):  
F. M. Kuhlmann ◽  
R. O. Laine ◽  
S Afrin ◽  
R Nakajima ◽  
M Akhtar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Human Infection ◽  
Middle Income ◽  
Symptomatic Disease ◽  
E Coli ◽  
Middle Income Countries ◽  
Colonization Factor ◽  
Specific Antigens ◽  
Colonization Factors

Enterotoxigenic E. coli (ETEC) contribute significantly to the substantial burden of infectious diarrhea among children living in low and middle income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as non-diarrheal sequelae related to these infections including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches defined by a subset of ETEC pathovar-specific antigens known as colonization factors (CFs). To identify additional conserved immunogens unique to this pathovar we employed an “open-aperture” approach to capture all potential conserved ETEC surface antigens in which we mined genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n=118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n=52), and toxin subunits. These arrays were then used to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this approach, we found that immune responses were largely constrained to a small number of antigens including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children < 2 years of age, both EtpA and a second antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for antigens not presently targeted by vaccines (non-canonical) in virulence and the development of adaptive immune responses during ETEC infections. These findings that may inform vaccine design efforts to complement existing approaches.

scholarly journals The Complete Genome of the Atypical Enteropathogenic Escherichia coli Archetype Isolate E110019 Highlights a Role for Plasmids in Dissemination of the Type III Secreted Effector EspT

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Tracy H. Hazen ◽  
David A. Rasko
Keyword(s):  
Escherichia Coli ◽  
Complete Genome ◽  
Genomic Analysis ◽  
Host Cells ◽  
Comparative Genomic ◽  
Content Type ◽  
E Coli ◽  
Type Iii ◽  
Severe Diarrhea ◽  
Typical Epec

ABSTRACT Enteropathogenic Escherichia coli (EPEC) is a leading cause of moderate to severe diarrhea among young children in developing countries, and EPEC isolates can be subdivided into two groups. Typical EPEC (tEPEC) bacteria are characterized by the presence of both the locus of enterocyte effacement (LEE) and the plasmid-encoded bundle-forming pilus (BFP), which are involved in adherence and translocation of type III effectors into the host cells. Atypical EPEC (aEPEC) bacteria also contain the LEE but lack the BFP. In the current report, we describe the complete genome of outbreak-associated aEPEC isolate E110019, which carries four plasmids. Comparative genomic analysis demonstrated that the type III secreted effector EspT gene, an autotransporter gene, a hemolysin gene, and putative fimbrial genes are all carried on plasmids. Further investigation of 65 espT-containing E. coli genomes demonstrated that different espT alleles are associated with multiple plasmids that differ in their overall gene content from the E110019 espT-containing plasmid. EspT has been previously described with respect to its role in the ability of E110019 to invade host cells. While other type III secreted effectors of E. coli have been identified on insertion elements and prophages of the chromosome, we demonstrated in the current study that the espT gene is located on multiple unique plasmids. These findings highlight a role of plasmids in dissemination of a unique E. coli type III secreted effector that is involved in host invasion and severe diarrheal illness.

scholarly journals Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi

2016 ◽  
Vol 113 (26) ◽  
pp. 7231-7236 ◽  
Author(s):  
Robert W. Moon ◽  
Hazem Sharaf ◽  
Claire H. Hastings ◽  
Yung Shwen Ho ◽  
Mridul B. Nair ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Plasmodium Knowlesi ◽  
Binding Protein ◽  
Cynomolgus Macaque ◽  
Genomic Analysis ◽  
Human Infection ◽  
Comparative Genomic ◽  
Gene Encoding ◽  
Human Rbcs

The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

scholarly journals Comparative Genomic Analysis Confirms Five Genetic Populations of the Select Agent, Rathayibacter toxicus

2020 ◽  
Vol 8 (3) ◽  
pp. 366
Author(s):  
Jarred Yasuhara-Bell ◽  
Mohammad Arif ◽  
Grethel Y. Busot ◽  
Rachel Mann ◽  
Brendan Rodoni ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
The United States ◽  
Grass Species ◽  
Comparative Genomic ◽  
Underrepresented Populations ◽  
System A ◽  
Genome Wide ◽  
The Family ◽  
Study Support ◽  
Genomic Regions

Rathayibacter toxicus is a Gram-positive, nematode-vectored bacterium that infects several grass species in the family Poaceae. Unique in its genus, R. toxicus has the smallest genome, possesses a complete CRISPR-Cas system, a vancomycin-resistance cassette, produces tunicamycin, a corynetoxin responsible for livestock deaths in Australia, and is designated a Select Agent in the United States. In-depth, genome-wide analyses performed in this study support the previously designated five genetic populations, with a core genome comprising approximately 80% of the genome for all populations. Results varied as a function of the type of analysis and when using different bioinformatics tools for the same analysis; e.g., some programs failed to identify specific genomic regions that were actually present. The software variance highlights the need to verify bioinformatics results by additional methods; e.g., PCR, mapping genes to genomes, use of multiple algorithms). These analyses suggest the following relationships among populations: RT-IV ↔ RT-I ↔ RT-II ↔ RT-III ↔ RT-V, with RT-IV and RT-V being the most unrelated. This is the most comprehensive analysis of R. toxicus that included populations RT-I and RT-V. Future studies require underrepresented populations and more recent isolates from varied hosts and geographic locations.

Comparative genomic analysis ofAcidithiobacillus ferrooxidansstrains using theA. ferrooxidansATCC 23270 whole-genome oligonucleotide microarray

2009 ◽  
Vol 55 (5) ◽  
pp. 587-598 ◽  
Author(s):  
Hailang Luo ◽  
Li Shen ◽  
Huaqun Yin ◽  
Qian Li ◽  
Qijiong Chen ◽  
...  
Keyword(s):  
Phylogenetic Tree ◽  
Evolutionary Relationship ◽  
Genomic Analysis ◽  
Oligonucleotide Microarray ◽  
Open Reading Frames ◽  
Genomic Diversity ◽  
Extracellular Polysaccharides ◽  
Comparative Genomic ◽  
Mining Areas ◽  
Main Factor

Acidithiobacillus ferrooxidans is an important microorganism used in biomining operations for metal recovery. Whole-genomic diversity analysis based on the oligonucleotide microarray was used to analyze the gene content of 12 strains of A. ferrooxidans purified from various mining areas in China. Among the 3100 open reading frames (ORFs) on the slides, 1235 ORFs were absent in at least 1 strain of bacteria and 1385 ORFs were conserved in all strains. The hybridization results showed that these strains were highly diverse from a genomic perspective. The hybridization results of 4 major functional gene categories, namely electron transport, carbon metabolism, extracellular polysaccharides, and detoxification, were analyzed. Based on the hybridization signals obtained, a phylogenetic tree was built to analyze the evolution of the 12 tested strains, which indicated that the geographic distribution was the main factor influencing the strain diversity of these strains. Based on the hybridization signals of genes associated with bioleaching, another phylogenetic tree showed an evolutionary relationship from which the co-relation between the clustering of specific genes and geochemistry could be observed. The results revealed that the main factor was geochemistry, among which the following 6 factors were the most important: pH, Mg, Cu, S, Fe, and Al.

scholarly journals A Bayesian implementation of the multispecies coalescent model with introgression for comparative genomic analysis

2019 ◽  
Author(s):  
Thomas Flouris ◽  
Xiyun Jiao ◽  
Bruce Rannala ◽  
Ziheng Yang
Keyword(s):  
Gene Flow ◽  
Genomic Sequence ◽  
Sequence Data ◽  
Incomplete Lineage Sorting ◽  
Mosquito Species ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Lineage Sorting ◽  
Multispecies Coalescent ◽  
Important Means

AbstractRecent analyses suggest that cross-species gene flow or introgression is common in nature, especially during species divergences. Genomic sequence data can be used to infer introgression events and to estimate the timing and intensity of introgression, providing an important means to advance our understanding of the role of gene flow in speciation. Here we implement the multispecies-coalescent-with-introgression (MSci) model, an extension of the multispecies-coalescent (MSC) model to incorporate introgression, in our Bayesian Markov chain Monte Carlo (MCMC) program BPP. The MSci model accommodates deep coalescence (or incomplete lineage sorting) and introgression and provides a natural framework for inference using genomic sequence data. Computer simulation confirms the good statistical properties of the method, although hundreds or thousands of loci are typically needed to estimate introgression probabilities reliably. Re-analysis of datasets from the purple cone spruce confirms the hypothesis of homoploid hybrid speciation. We estimated the introgression probability using the genomic sequence data from six mosquito species in the Anopheles gambiae species complex, which varies considerably across the genome, likely driven by differential selection against introgressed alleles.

scholarly journals Eutherian comparative genomic analysis protocol

2020 ◽  
Author(s):  
Marko Premzl
Keyword(s):  
Genomic Sequence ◽  
Sequence Data ◽  
Genomic Analysis ◽  
Comparative Genomic Analysis ◽  
Third Party ◽  
Comparative Genomic ◽  
Data Sets ◽  
Gene Data ◽  
Sequence Errors ◽  
Analysis Protocol

Abstract The eutherian genomics momentum greatly advanced biology and medicine. Nevertheless, future revisions and updates of eutherian genomic sequence data sets were expected, due to potential genomic sequence errors and incompleteness of genomic sequences. The eutherian comparative genomic analysis protocol was established as guidance in protection against potential genomic sequence errors in public eutherian genomic sequence assemblies. The protocol revised, updated and published 12 major eutherian gene data sets, including 1853 complete coding sequences deposited in European Nucleotide Archive as curated third party data gene data sets under accession numbers: FR734011-FR734074, HF564658-HF564785, HF564786-HF564815, HG328835-HG329089, HG426065-HG426183, HG931734-HG931849, LM644135-LM644234, LN874312-LN874522, LT548096-LT548244, LT631550-LT631670, LT962964-LT963174 and LT990249-LT990597.

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