Responses of the Human GutEscherichia coliPopulation to Pathogen and Antibiotic Disturbances

ABSTRACTStudies ofEscherichia coliin the human gastrointestinal tract have focused on pathogens, such as diarrhea-causing enterotoxigenicE. coli(ETEC), while overlooking the resident, nonpathogenicE. colicommunity. Relatively few genomes of nonpathogenicE. colistrains are available for comparative genomic analysis, and the ecology of these strains is poorly understood. This study examined the diversity and dynamics of resident human gastrointestinalE. colicommunities in the face of the ecological challenges presented by pathogen (ETEC) challenge, as well as of antibiotic treatment. Whole-genome sequences obtained fromE. coliisolates from before, during, and after ETEC challenge were used in phylogenomic and comparative genomic analyses to examine the diversity of the residentE. colicommunities, as well as the dynamics of the challenge strain, H10407, a well-studied ETEC strain (serotype O78:H11) that produces both heat-labile and heat-stable enterotoxins. ETEC failed to become the dominantE. coliclone in two of the six challenge subjects, each of whom exhibited limited or no clinical presentation of diarrhea. TheE. colicommunities of the remaining four subjects became ETEC dominant during the challenge but reverted to their original, subject-specific populations following antibiotic treatment, suggesting resiliency of the residentE. colipopulation following major ecological disruptions. This resiliency is likely due in part to the abundance of antibiotic-resistant ST131E. colistrains in the resident populations. This report provides valuable insights into the potential interactions of members of the gastrointestinal microbiome and its responses to challenge by an external pathogen and by antibiotic exposure.IMPORTANCEResearch on human-associatedE. colitends to focus on pathogens, such as enterotoxigenicE. coli(ETEC) strains, which are a leading cause of diarrhea in developing countries. However, the severity of disease caused by these pathogens is thought to be influenced by the microbiome. The nonpathogenicE. colicommunity that resides in the human gastrointestinal tract may play a role in pathogen colonization and disease severity and may become a reservoir for virulence and antibiotic resistance genes. Our study used whole-genome sequencing ofE. colibefore, during, and after challenge with an archetype ETEC isolate, H10407, and antibiotic treatment to explore the diversity and resiliency of the residentE. colipopulation in response to the ecological disturbances caused by pathogen invasion and antibiotic treatment.

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Temporal Variability ofEscherichia coliDiversity in the Gastrointestinal Tracts of Tanzanian Children with and without Exposure to Antibiotics

mSphere ◽

10.1128/msphere.00558-18 ◽

2018 ◽

Vol 3 (6) ◽

Cited By ~ 9

Author(s):

Taylor K. S. Richter ◽

Tracy H. Hazen ◽

Diana Lam ◽

Christian L. Coles ◽

Jessica C. Seidman ◽

...

Keyword(s):

Escherichia Coli ◽

Gastrointestinal Tract ◽

Antimicrobial Resistance ◽

Antibiotic Treatment ◽

Genomic Diversity ◽

Human Gastrointestinal Tract ◽

Content Type ◽

E Coli ◽

Time Points ◽

Antimicrobial Resistance Genes

ABSTRACTThe stability of theEscherichia colipopulations in the human gastrointestinal tract is not fully appreciated, and represents a significant knowledge gap regarding gastrointestinal community structure, as well as resistance to incoming pathogenic bacterial species and antibiotic treatment. The current study examines the genomic content of 240Escherichia coliisolates from 30 children, aged 2 to 35 months old, in Tanzania. TheE. colistrains were isolated from three time points spanning a six-month time period, with and without antibiotic treatment. The resulting isolates were sequenced, and the genomes compared. The findings in this study highlight the transient nature ofE. colistrains in the gastrointestinal tract of these children, as during a six-month interval, no one individual contained phylogenomically related isolates at all three time points. While the majority of the isolates at any one time point were phylogenomically similar, most individuals did not contain phylogenomically similar isolates at more than two time points. Examination of global genome content, canonicalE. colivirulence factors, multilocus sequence type, serotype, and antimicrobial resistance genes identified diversity even among phylogenomically similar strains. There was no apparent increase in the antimicrobial resistance gene content after antibiotic treatment. The examination of theE. colifrom longitudinal samples from multiple children in Tanzania provides insight into the genomic diversity and population variability of residentE. coliwithin the rapidly changing environment of the gastrointestinal tract of these children.IMPORTANCEThis study increases the number of residentEscherichia coligenome sequences, and exploresE. colidiversity through longitudinal sampling. We investigate the genomes ofE. coliisolated from human gastrointestinal tracts as part of an antibiotic treatment program among rural Tanzanian children. Phylogenomics demonstrates that residentE. coliare diverse, even within a single host. Though theE. coliisolates of the gastrointestinal community tend to be phylogenomically similar at a given time, they differed across the interrogated time points, demonstrating the variability of the members of theE. colicommunity in these subjects. Exposure to antibiotic treatment did not have an apparent impact on theE. colicommunity or the presence of resistance and virulence genes withinE. coligenomes. The findings of this study highlight the variable nature of specific bacterial members of the human gastrointestinal tract.

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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

Infection and Immunity ◽

10.1128/iai.00412-19 ◽

2019 ◽

Vol 87 (10) ◽

Cited By ~ 1

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.

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Whole-Genome Sequences and Classification of Streptococcus agalactiae Strains Isolated from Laboratory-Reared Long-Evans Rats (Rattus norvegicus)

Genome Announcements ◽

10.1128/genomea.01435-16 ◽

2017 ◽

Vol 5 (1) ◽

Cited By ~ 4

Author(s):

C. Bodi Winn ◽

J. Dzink-Fox ◽

Y. Feng ◽

Z. Shen ◽

V. Bakthavatchalu ◽

...

Keyword(s):

Streptococcus Agalactiae ◽

Genomic Analysis ◽

Opportunistic Pathogen ◽

Comparative Genomic ◽

Whole Genome ◽

Genome Sequences ◽

Content Type ◽

Long Evans ◽

Fatal Septicemia

ABSTRACT In collaboration with the CDC’s Streptococcus Laboratory, we report here the whole-genome sequences of seven Streptococcus agalactiae bacteria isolated from laboratory-reared Long-Evans rats. Four of the S. agalactiae isolates were associated with morbidity accompanied by endocarditis, metritis, and fatal septicemia, providing an opportunity for comparative genomic analysis of this opportunistic pathogen.

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

Journal of Bacteriology ◽

10.1128/jb.00619-08 ◽

2008 ◽

Vol 190 (20) ◽

pp. 6881-6893 ◽

Cited By ~ 499

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.

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Diversity and Population Overlap between Avian and HumanEscherichia coliBelonging to Sequence Type 95

mSphere ◽

10.1128/msphere.00333-18 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 11

Author(s):

Steffen L. Jørgensen ◽

Marc Stegger ◽

Eglé Kudirkiene ◽

Berit Lilje ◽

Louise L. Poulsen ◽

...

Keyword(s):

Urinary Tract ◽

Urinary Tract Infections ◽

Large Scale ◽

Sequence Type ◽

Comparative Genomic ◽

Avian Host ◽

Whole Genome ◽

Content Type ◽

E Coli ◽

Tract Infections

ABSTRACTAvian-pathogenicEscherichia coli(APEC) is a subgroup of extraintestinal pathogenicE.coli(ExPEC) presumed to be zoonotic and to represent an external reservoir for extraintestinal infections in humans, including uropathogenicE. coli(UPEC) causing urinary tract infections. Comparative genomics has previously been applied to investigate whether APEC and human ExPEC are distinct entities. Even so, whole-genome-based studies are limited, and large-scale comparisons focused on single sequence types (STs) are not available yet. In this study, comparative genomic analysis was performed on 323 APEC and human ExPEC genomes belonging to sequence type 95 (ST95) to investigate whether APEC and human ExPEC are distinct entities. Our study showed that APEC of ST95 did not constitute a unique ExPEC branch and was genetically diverse. A large genetic overlap between APEC and certain human ExPEC was observed, with APEC located on multiple branches together with closely related human ExPEC, including nearly identical APEC and human ExPEC. These results illustrate that certain ExPEC clones may indeed have the potential to cause infection in both poultry and humans. Previously described ExPEC-associated genes were found to be encoded on ColV plasmids. These virulence-associated plasmids seem to be crucial for ExPEC strains to cause avian colibacillosis and are strongly associated with strains of the mixed APEC/human ExPEC clusters. The phylogenetic analysis revealed two distinct branches consisting of exclusively closely related human ExPEC which did not carry the virulence-associated plasmids, emphasizing a lower avian virulence potential of human ExPEC in relation to an avian host.IMPORTANCEAPEC causes a range of infections in poultry, collectively called colibacillosis, and is the leading cause of mortality and is associated with major economic significance in the poultry industry. A growing number of studies have suggested APEC as an external reservoir of human ExPEC, including UPEC, which is a reservoir. ExPEC belonging to ST95 is considered one of the most important pathogens in both poultry and humans. This study is the first in-depth whole-genome-based comparison of ST95E. coliwhich investigates both the core genomes as well as the accessory genomes of avian and human ExPEC. We demonstrated that multiple lineages of ExPEC belonging to ST95 exist, of which the majority may cause infection in humans, while only part of the ST95 cluster seem to be avian pathogenic. These findings further support the idea that urinary tract infections may be a zoonotic infection.

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In SilicoTyping and Comparative Genomic Analysis of IncFIIKPlasmids and Insights into the Evolution of Replicons, Plasmid Backbones, and Resistance Determinant Profiles

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00764-18 ◽

2018 ◽

Vol 62 (10) ◽

Cited By ~ 8

Author(s):

Dexi Bi ◽

Jiayi Zheng ◽

Jun-Jie Li ◽

Zi-Ke Sheng ◽

Xingchen Zhu ◽

...

Keyword(s):

Large Scale ◽

Antibiotic Resistance Genes ◽

Genomic Analysis ◽

Epidemiological Studies ◽

Genome Comparison ◽

Comparative Genomic ◽

Content Type ◽

Bacterial Plasmid ◽

Phylogeny And Evolution ◽

Sequence Types

ABSTRACTIncFIIKplasmids are associated with the acquisition and dissemination of multiple-antimicrobial resistance inKlebsiella pneumoniaeand often encountered in clinical isolates of this species. Since the phylogeny and evolution of IncFIIKplasmids remain unclear, here we performed large-scalein silicotyping and comparative analysis of these plasmids in publicly available bacterial/plasmid genomes. IncFIIKplasmids are prevalent inK. pneumoniae, being found in 69% of sequenced genomes, covering 66% of sequenced STs (sequence types), but sparse in otherEnterobacteriaceae. IncFIIKreplicons have three lineages. One IncFIIKallele could be found in distinctK. pneumoniaeSTs, highlighting the lateral genetic flow of IncFIIKplasmids. A set of 77 IncFIIKplasmids with full sequences were further analyzed. A pool of 327 antibiotic resistance genes or remnants were annotated in 75.3% of these plasmids. Plasmid genome comparison reiterated that they often contain other replicons belonging to IncFIA, IncFIB, IncFIIYp, IncFIIpCRY, IncR, IncL, and IncN groups and that they share a conserved backbone featuring an F-like conjugation module that has divergent components responsible for regulation and mating pair stabilization. Further epidemiological studies of IncFIIKplasmids are required due to the sample bias ofK. pneumoniaegenomes in public databases. This study provides insights into the evolution and structures of IncFIIKplasmids.

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Whole-Genome Sequence of Bifidobacterium longum Strain Indica, Isolated from the Gut of a Healthy Indian Adult

Genome Announcements ◽

10.1128/genomea.01017-17 ◽

2017 ◽

Vol 5 (41) ◽

Cited By ~ 1

Author(s):

Satyabrata Bag ◽

Tarini Shankar Ghosh ◽

Bhabatosh Das

Keyword(s):

Gastrointestinal Tract ◽

Genome Sequence ◽

Anaerobic Bacterium ◽

Acid Metabolism ◽

Intestinal Inflammation ◽

Bifidobacterium Longum ◽

Whole Genome Sequence ◽

Whole Genome ◽

Human Gastrointestinal Tract ◽

Content Type

ABSTRACT Bifidobacterium longum, a Gram-positive rod-shaped anaerobic bacterium, inhabits the human gastrointestinal tract and contributes significantly to oligosaccharide production, amino acid metabolism, and protection against intestinal inflammation. Here, we report the whole-genome sequence of B. longum, which was isolated from the gastrointestinal tract of a healthy Indian adult.

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Investigating the Relatedness of Enteroinvasive Escherichia coli to Other E. coli and Shigella Isolates by Using Comparative Genomics

Infection and Immunity ◽

10.1128/iai.00350-16 ◽

2016 ◽

Vol 84 (8) ◽

pp. 2362-2371 ◽

Cited By ~ 23

Author(s):

Tracy H. Hazen ◽

Susan R. Leonard ◽

Keith A. Lampel ◽

David W. Lacher ◽

Anthony T. Maurelli ◽

...

Keyword(s):

Escherichia Coli ◽

Genomic Analysis ◽

Host Cells ◽

Comparative Genomic ◽

Virulence Plasmid ◽

Phylogenomic Analysis ◽

Content Type ◽

E Coli ◽

Associated Proteins ◽

Human Illness

EnteroinvasiveEscherichia coli(EIEC) is a unique pathovar that has a pathogenic mechanism nearly indistinguishable from that ofShigellaspecies. In contrast to isolates of the fourShigellaspecies, which are widespread and can be frequent causes of human illness, EIEC causes far fewer reported illnesses each year. In this study, we analyzed the genome sequences of 20 EIEC isolates, including 14 first described in this study. Phylogenomic analysis of the EIEC genomes demonstrated that 17 of the isolates are present in three distinct lineages that contained only EIEC genomes, compared to reference genomes from each of theE. colipathovars andShigellaspecies. Comparative genomic analysis identified genes that were unique to each of the three identified EIEC lineages. While many of the EIEC lineage-specific genes have unknown functions, those with predicted functions included a colicin and putative proteins involved in transcriptional regulation or carbohydrate metabolism.In silicodetection of theShigellavirulence plasmid (pINV), which is essential for the invasion of host cells, demonstrated that a form of pINV was present in nearly all EIEC genomes, but the Mxi-Spa-Ipa region of the plasmid that encodes the invasion-associated proteins was absent from several of the EIEC isolates. The comparative genomic findings in this study support the hypothesis that multiple EIEC lineages have evolved independently from multiple distinct lineages ofE. colivia the acquisition of theShigellavirulence plasmid and, in some cases, theShigellapathogenicity islands.

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Characterization and Comparative Genomic Analysis of a Novel Bacteriophage, SFP10, Simultaneously Inhibiting both Salmonella enterica and Escherichia coli O157:H7

Applied and Environmental Microbiology ◽

10.1128/aem.06231-11 ◽

2011 ◽

Vol 78 (1) ◽

pp. 58-69 ◽

Cited By ~ 84

Author(s):

Minjung Park ◽

Ju-Hoon Lee ◽

Hakdong Shin ◽

Minsik Kim ◽

Jeongjoon Choi ◽

...

Keyword(s):

Escherichia Coli ◽

Salmonella Enterica ◽

Burst Size ◽

Genomic Analysis ◽

Comparative Genomic ◽

Tail Fiber ◽

Content Type ◽

E Coli ◽

Development Of Resistance

ABSTRACTSalmonella entericaandEscherichia coliO157:H7 are major food-borne pathogens causing serious illness. Phage SFP10, which revealed effective infection of bothS. entericaandE. coliO157:H7, was isolated and characterized. SFP10 contains a 158-kb double-stranded DNA genome belonging to the Vi01 phage-like familyMyoviridae.In vitroadsorption assays showed that the adsorption constant rates to bothSalmonella entericaserovar Typhimurium andE. coliO157:H7 were 2.50 × 10−8ml/min and 1.91 × 10−8ml/min, respectively. One-step growth analysis revealed that SFP10 has a shorter latent period (25 min) and a larger burst size (>200 PFU) than ordinaryMyoviridaephages, suggesting effective host infection and lytic activity. However, differential development of resistance to SFP10 inS.Typhimurium andE. coliO157:H7 was observed; bacteriophage-insensitive mutant (BIM) frequencies of 1.19 × 10−2CFU/ml forS.Typhimurium and 4.58 × 10−5CFU/ml forE. coliO157:H7 were found, indicating that SFP10 should be active and stable for control ofE. coliO157:H7 with minimal emergence of SFP10-resistant pathogens but may not be forS.Typhimurium. Specific mutation ofrfaLinS.Typhimurium andE. coliO157:H7 revealed the O antigen as an SFP10 receptor for both bacteria. Genome sequence analysis of SFP10 and its comparative analysis with homologousSalmonellaVi01 andShigellaphiSboM-AG3 phages revealed that their tail fiber and tail spike genes share low sequence identity, implying that the genes are major host specificity determinants. This is the first report identifying specific infection and inhibition ofSalmonellaTyphimurium andE. coliO157:H7 by a single bacteriophage.

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Population dynamics of Escherichia coli in the gastrointestinal tracts of Tanzanian children

10.1101/294934 ◽

2018 ◽

Author(s):

Taylor K. S. Richter ◽

Tracy H. Hazen ◽

Diana Lam ◽

Christian L. Coles ◽

Jessica C. Seidman ◽

...

Keyword(s):

Escherichia Coli ◽

Gastrointestinal Tract ◽

Antimicrobial Resistance ◽

Antibiotic Treatment ◽

Genomic Diversity ◽

Human Gastrointestinal Tract ◽

E Coli ◽

Time Points ◽

Antimicrobial Resistance Genes ◽

Variable Nature

AbstractThe stability of the Escherichia coli populations in the human gastrointestinal tract are not fully appreciated, and represent a significant knowledge gap regarding gastrointestinal community structure, as well as resistance to incoming pathogenic bacterial species and antibiotic treatment. The current study examines the genomic content of 240 Escherichia coli isolates from children 2 to 35 months old in Tanzania. The E. coli strains were isolated from three time points spanning a six month time period, with or without antibiotic treatment. The resulting isolates were sequenced, and the genomes compared. The findings in this study highlight the transient nature of E. coli strains in the gastrointestinal tract of children, as during a six-month interval, no one individual contained phylogenomically related isolates at all three time points. While the majority of the isolates at any one time point were phylogenomically similar, most individuals did not contain phylogenomically similar isolates at more than two time points. Examination of global genome content, canonical E. coli virulence factors, multilocus sequence type, serotype, and antimicrobial resistance genes identified diversity even among phylogenomically similar strains. There was no apparent increase in the antimicrobial resistance gene content after antibiotic treatment. The examination of the E. coli from longitudinal samples from multiple children in Tanzania provides insight into the genomic diversity and population variability of resident E. coli within the rapidly changing environment of the gastrointestinal tract.ImportanceThis study increases the number of resident Escherichia coli genome sequences, and explores E. coli diversity through longitudinal sampling. We investigate the genomes of E. coli isolated from human gastrointestinal tracts as part of an antibiotic treatment program among rural Tanzanian children. Phylogenomics demonstrates that resident E. coli are diverse, even within a single host. Though the E. coli isolates of the gastrointestinal community tend to be phylogenomically similar at a given time, they differed across the interrogated time points, demonstrating the variability of the members of the E. coli community. Exposure to antibiotic treatment did not have an apparent impact on the E. coli community or the presence of resistance and virulence genes within E. coli genomes. The findings of this study highlight the variable nature of bacterial members of the human gastrointestinal tract.

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