Faculty Opinions recommendation of Computational identification of noncoding RNAs in E. coli by comparative genomics.

Hfq is a bacterial regulator with key roles in gene expression. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, thanks to its binding to small regulatory noncoding RNAs. This property is of primary importance for bacterial adaptation and survival in hosts. Small RNAs and Hfq are, for instance, involved in the response to antibiotics. Previous work has shown that the E. coli Hfq C-terminal region (Hfq-CTR) self-assembles into an amyloid structure. It was also demonstrated that the green tea compound EpiGallo Catechin Gallate (EGCG) binds to Hfq-CTR amyloid fibrils and remodels them into nonamyloid structures. Thus, compounds that target the amyloid region of Hfq may be used as antibacterial agents. Here, we show that another compound that inhibits amyloid formation, apomorphine, may also serve as a new antibacterial. Our results provide an alternative in order to repurpose apomorphine, commonly used in the treatment of Parkinson’s disease, as an antibiotic to block bacterial adaptation to treat infections.

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E. coli NF73-1 Isolated From NASH Patients Aggravates NAFLD in Mice by Translocating Into the Liver and Stimulating M1 Polarization

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.535940 ◽

2020 ◽

Vol 10 ◽

Author(s):

Yifan Zhang ◽

Weiwei Jiang ◽

Jun Xu ◽

Na Wu ◽

Yang Wang ◽

...

Keyword(s):

Gene Expression ◽

Comparative Genomics ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Normal Diet ◽

Specific Gene ◽

Whole Genome ◽

Metabolic Switch ◽

M1 Macrophages ◽

E Coli

ObjectiveThe gut microbiota is associated with nonalcoholic fatty liver disease (NAFLD). We isolated the Escherichia coli strain NF73-1 from the intestines of a NASH patient and then investigated its effect and underlying mechanism.Methods16S ribosomal RNA (16S rRNA) amplicon sequencing was used to detect bacterial profiles in healthy controls, NAFLD patients and NASH patients. Highly enriched E. coli strains were cultured and isolated from NASH patients. Whole-genome sequencing and comparative genomics were performed to investigate gene expression. Depending on the diet, male C57BL/6J mice were further grouped in normal diet (ND) and high-fat diet (HFD) groups. To avoid disturbing the bacterial microbiota, some of the ND and HFD mice were grouped as “bacteria-depleted” mice and treated with a cocktail of broad-spectrum antibiotic complex (ABX) from the 8th to 10th week. Then, E. coli NF73-1, the bacterial strain isolated from NASH patients, was administered transgastrically for 6 weeks to investigate its effect and mechanism in the pathogenic progression of NAFLD.ResultsThe relative abundance of Escherichia increased significantly in the mucosa of NAFLD patients, especially NASH patients. The results from whole-genome sequencing and comparative genomics showed a specific gene expression profile in E. coli strain NF73-1, which was isolated from the intestinal mucosa of NASH patients. E. coli NF73-1 accelerates NAFLD independently. Only in the HFD-NF73-1 and HFD-ABX-NF73-1 groups were EGFP-labeled E. coli NF73-1 detected in the liver and intestine. Subsequently, translocation of E. coli NF73-1 into the liver led to an increase in hepatic M1 macrophages via the TLR2/NLRP3 pathway. Hepatic M1 macrophages induced by E. coli NF73-1 activated mTOR-S6K1-SREBP-1/PPAR-α signaling, causing a metabolic switch from triglyceride oxidation toward triglyceride synthesis in NAFLD mice.ConclusionsE. coli NF73-1 is a critical trigger in the progression of NAFLD. E. coli NF73-1 might be a specific strain for NAFLD patients.

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Comparative Genomics ofEscherichia coliIsolated from Skin and Soft Tissue and Other Extraintestinal Infections

mBio ◽

10.1128/mbio.01070-17 ◽

2017 ◽

Vol 8 (4) ◽

Cited By ~ 12

Author(s):

Amit Ranjan ◽

Sabiha Shaik ◽

Nishant Nandanwar ◽

Arif Hussain ◽

Sumeet K. Tiwari ◽

...

Keyword(s):

Escherichia Coli ◽

Comparative Genomics ◽

Soft Tissue ◽

Multidrug Resistant ◽

Primary Concern ◽

Beta Lactamase ◽

Soft Tissue Infections ◽

E Coli ◽

Recent Emergence ◽

Tract Infections

ABSTRACTEscherichia coli, an intestinal Gram-negative bacterium, has been shown to be associated with a variety of diseases in addition to intestinal infections, such as urinary tract infections (UTIs), meningitis in neonates, septicemia, skin and soft tissue infections (SSTIs), and colisepticemia. Thus, for nonintestinal infections, it is categorized as extraintestinal pathogenicE. coli(ExPEC). It is also an opportunistic pathogen, causing cross infections, notably as an agent of zoonotic diseases. However, comparative genomic data providing functional and genetic coordinates for ExPEC strains associated with these different types of infections have not proven conclusive. In the study reported here, ExPECE. coliisolated from SSTIs was characterized, including virulence and drug resistance profiles, and compared with isolates from patients suffering either pyelonephritis or septicemia. Results revealed that the majority of the isolates belonged to two pathogenic phylogroups, B2 and D. Approximately 67% of the isolates were multidrug resistant (MDR), with 85% producing extended-spectrum beta-lactamase (ESBL) and 6% producing metallo-beta-lactamase (MBL). TheblaCTX-M-15genotype was observed in at least 70% of theE. coliisolates in each category, conferring resistance to an extended range of beta-lactam antibiotics. Whole-genome sequencing and comparative genomics of the ExPEC isolates revealed that two of the four isolates from SSTIs, NA633 and NA643, belong to pandemic sequence type ST131, whereas functional characteristics of three of the ExPEC pathotypes revealed that they had equal capabilities to form biofilm and were resistant to human serum. Overall, the isolates from a variety of ExPEC infections demonstrated similar resistomes and virulomes and did not display any disease-specific functional or genetic coordinates.IMPORTANCEInfections caused by extraintestinal pathogenicE. coli(ExPEC) are of global concern as they result in significant costs to health care facilities management. The recent emergence of a multidrug-resistant pandemic clone,Escherichia coliST131, is of primary concern as a global threat. In developing countries, such as India, skin and soft tissue infections (SSTIs) associated withE. coliare marginally addressed. In this study, we employed both genomic analysis and phenotypic assays to determine relationships, if any, among the ExPEC pathotypes. Similarity between antibiotic resistance and virulence profiles was observed, ST131 isolates from SSTIs were reported, and genomic similarities among strains isolated from different disease conditions were detected. This study provides functional molecular infection epidemiology insight into SSTI-associatedE. colicompared with ExPEC pathotypes.

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First Report and Comparative Genomics Analysis of a blaOXA-244–Harbouring Escherichia coli Isolate Recovered in American Continent

10.20944/preprints201909.0150.v1 ◽

2019 ◽

Author(s):

Deisy J Abril ◽

Ingrid Gisell Bustos Moya ◽

Ricaurte Alejandro Marquez-Ortiz ◽

Diego Fernando Josa Montero ◽

Zayda Lorena Corredor Rozo ◽

...

Keyword(s):

Escherichia Coli ◽

Comparative Genomics ◽

Genomic Island ◽

Genomic Analysis ◽

American Continent ◽

Incompatibility Group ◽

Coli Isolate ◽

First Report ◽

E Coli ◽

Comparative Genomics Analysis

The carbapenemase OXA-244 is a derivate of OXA-48, and its detection is very difficult in laboratories. Here we report the identification and genomic analysis of an Escherichia coli isolate (28Eco12) harbouring the blaOXA-244 gene identified in Colombia, South America. The 28Eco12 isolate was identified during a retrospective study and it was recovered from a patient treated in Colombia. The complete nucleotide sequence was established using the PacBio platform. A comparative genomics analysis with other blaOXA-244–harbouring Escherichia coli strains was performed. The 28Eco12 isolate belonged to sequence type (ST) 38 and its genome was composed of two molecules, a chromosome of 5,343,367 bp and a plasmid of 92,027 bp, which belonged to the incompatibility group IncY and did not harbour resistance genes. The blaOXA-244 gene was chromosomally-encoded and mobilized by an ISR1-related Tn6237 composite transposon. Notably, this transposon was inserted and located within a new genomic island. For our knowledge this is the first report of a blaOXA-244–harbouring Escherichia coli isolate in American continent.Our results suggest that the introduction of the OXA-244-producing E. coli isolate was through clonal expansion of the ST38 pandemic clone. Other isolates producing OXA-244 could be circulating silently on the American continent.

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Comparative Genomics of an IncA/C Multidrug Resistance Plasmid from Escherichia coli and Klebsiella Isolates from Intensive Care Unit Patients and the Utility of Whole-Genome Sequencing in Health Care Settings

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02573-14 ◽

2014 ◽

Vol 58 (8) ◽

pp. 4814-4825 ◽

Cited By ~ 16

Author(s):

Tracy H. Hazen ◽

LiCheng Zhao ◽

Mallory A. Boutin ◽

Angela Stancil ◽

Gwen Robinson ◽

...

Keyword(s):

Escherichia Coli ◽

Health Care ◽

Intensive Care Unit ◽

Intensive Care ◽

Comparative Genomics ◽

Resistance Genes ◽

Whole Genome ◽

Content Type ◽

Health Care Settings ◽

E Coli

ABSTRACTThe IncA/C plasmids have been implicated for their role in the dissemination of β-lactamases, including gene variants that confer resistance to expanded-spectrum cephalosporins, which are often the treatment of last resort against multidrug-resistant, hospital-associated pathogens. AblaFOX-5gene was detected in 14Escherichia coliand 16Klebsiellaisolates that were cultured from perianal swabs of patients admitted to an intensive care unit (ICU) of the University of Maryland Medical Center (UMMC) in Baltimore, MD, over a span of 3 years. Four of the FOX-encoding isolates were obtained from subsequent samples of patients that were initially negative for an AmpC β-lactamase upon admission to the ICU, suggesting that the AmpC β-lactamase-encoding plasmid was acquired while the patient was in the ICU. The genomes of fiveE. coliisolates and sixKlebsiellaisolates containingblaFOX-5were selected for sequencing based on their plasmid profiles. An ∼167-kb IncA/C plasmid encoding the FOX-5 β-lactamase, a CARB-2 β-lactamase, additional antimicrobial resistance genes, and heavy metal resistance genes was identified. Another FOX-5-encoding IncA/C plasmid that was nearly identical except for a variable region associated with the resistance genes was also identified. To our knowledge, these plasmids represent the first FOX-5-encoding plasmids sequenced. We used comparative genomics to describe the genetic diversity of a plasmid encoding a FOX-5 β-lactamase relative to the whole-genome diversity of 11E. coliandKlebsiellaisolates that carry this plasmid. Our findings demonstrate the utility of whole-genome sequencing for tracking of plasmid and antibiotic resistance gene distribution in health care settings.

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Comparative genomics and transcriptomics of Escherichia coli isolates carrying virulence factors of both enteropathogenic and enterotoxigenic E. coli

Scientific Reports ◽

10.1038/s41598-017-03489-z ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 19

Author(s):

Tracy H. Hazen ◽

Jane Michalski ◽

Qingwei Luo ◽

Amol C. Shetty ◽

Sean C. Daugherty ◽

...

Keyword(s):

Escherichia Coli ◽

Comparative Genomics ◽

Virulence Factors ◽

E Coli

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Evolutionary Dynamics Based on Comparative Genomics of Pathogenic Escherichia coli Lineages Harboring Polyketide Synthase (pks) Island

mBio ◽

10.1128/mbio.03634-20 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Arya Suresh ◽

Sabiha Shaik ◽

Ramani Baddam ◽

Amit Ranjan ◽

Shamsul Qumar ◽

...

Keyword(s):

Comparative Genomics ◽

Maximum Likelihood ◽

High Throughput ◽

Core Genome ◽

Polyketide Synthase ◽

Clinical Implications ◽

Data Set ◽

Content Type ◽

E Coli ◽

The Core

ABSTRACT The genotoxin colibactin is a secondary metabolite produced by the polyketide synthase (pks) island harbored by extraintestinal pathogenic E. coli (ExPEC) and other members of the Enterobacteriaceae that has been increasingly reported to have critical implications in human health. The present study entails a high-throughput whole-genome comparison and phylogenetic analysis of such pathogenic E. coli isolates to gain insights into the patterns of distribution, horizontal transmission, and evolution of the island. For the current study, 23 pks-positive ExPEC genomes were newly sequenced, and their virulome and resistome profiles indicated a preponderance of virulence encoding genes and a reduced number of genes for antimicrobial resistance. In addition, 4,090 E. coli genomes from the public domain were also analyzed for large-scale screening for pks-positive genomes, out of which a total of 530 pks-positive genomes were studied to understand the subtype-based distribution pattern(s). The pks island showed a significant association with the B2 phylogroup (82.2%) and a high prevalence in sequence type 73 (ST73; n = 179) and ST95 (n = 110) and the O6:H1 (n = 110) serotype. Maximum-likelihood (ML) phylogeny of the core genome and intergenic regions (IGRs) of the ST95 model data set, which was selected because it had both pks-positive and pks-negative genomes, displayed clustering in relation to their carriage of the pks island. Prevalence patterns of genes encoding RM systems in the pks-positive and pks-negative genomes were also analyzed to determine their potential role in pks island acquisition and the maintenance capability of the genomes. Further, the maximum-likelihood phylogeny based on the core genome and pks island sequences from 247 genomes with an intact pks island demonstrated horizontal gene transfer of the island across sequence types and serotypes, with few exceptions. This study vitally contributes to understanding of the lineages and subtypes that have a higher propensity to harbor the pks island-encoded genotoxin with possible clinical implications. IMPORTANCE Extraintestinal pathologies caused by highly virulent strains of E. coli amount to clinical implications with high morbidity and mortality rates. Pathogenic E. coli strains are evolving with the horizontal acquisition of mobile genetic elements, including pathogenicity islands such as the pks island, which produces the genotoxin colibactin, resulting in severe clinical outcomes, including colorectal cancer progression. The current study encompasses high-throughput comparative genomics and phylogenetic analyses to address the questions pertaining to the acquisition and evolution pattern of the genomic island in different E. coli subtypes. It is crucial to gain insights into the distribution, transfer, and maintenance of pathogenic islands, as they harbor multiple virulence genes involved in pathogenesis and clinical implications of the infection.

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