scholarly journals Virulence of Enteropathogenic Escherichia coli, a Global Pathogen

2003 ◽  
Vol 16 (3) ◽  
pp. 365-378 ◽  
Author(s):  
S. C. Clarke ◽  
R. D. Haigh ◽  
P. P. E. Freestone ◽  
P. H. Williams
Keyword(s):  
Escherichia Coli ◽  
Host Cell ◽  
Type Iii Secretion ◽  
Pathogenic Bacteria ◽  
Diarrheal Disease ◽  
Lesion Site ◽  
Intimate Contact ◽  
E Coli ◽  
Enterocyte Effacement ◽  
Broad Overview

SUMMARY Enteropathogenic Escherichia coli (EPEC) remains an important cause of diarrheal disease worldwide. Research into EPEC is intense and provides a good virulence model of other E. coli infections as well as other pathogenic bacteria. Although the virulence mechanisms are now better understood, they are extremely complex and much remains to be learnt. The pathogenesis of EPEC depends on the formation of an ultrastructural lesion in which the bacteria make intimate contact with the host apical enterocyte membrane. The formation of this lesion is a consequence of the ability of EPEC to adhere in a localized manner to the host cell, aided by bundle-forming pili. Tyrosine phosphorylation and signal transduction events occur within the host cell at the lesion site, leading to a disruption of the host cell mechanisms and, consequently, to diarrhea. These result from the action of highly regulated EPEC secreted proteins which are released via a type III secretion system, many genes of which are located within a pathogenicity island known as the locus of enterocyte effacement. Over the last few years, dramatic increases in our knowledge of EPEC virulence have taken place. This review therefore aims to provide a broad overview of and update to the virulence aspects of EPEC.

scholarly journals Quorum-Sensing Escherichia coli Regulator A: a Regulator of the LysR Family Involved in the Regulation of the Locus of Enterocyte Effacement Pathogenicity Island in Enterohemorrhagic E. coli

2002 ◽  
Vol 70 (6) ◽  
pp. 3085-3093 ◽  
Author(s):  
Vanessa Sperandio ◽  
Caiyi C. Li ◽  
James B. Kaper
Keyword(s):  
Escherichia Coli ◽  
Quorum Sensing ◽  
Type Iii Secretion ◽  
Pathogenicity Island ◽  
The Other ◽  
E Coli ◽  
Type Iii ◽  
Enterocyte Effacement ◽  
K 12 ◽  
Lysr Family

ABSTRACT The locus of enterocyte effacement (LEE) is a chromosomal pathogenicity island that encodes the proteins involved in the formation of the attaching and effacing lesions by enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). The LEE comprises 41 open reading frames organized in five major operons, LEE1, LEE2, LEE3, tir (LEE5), and LEE4, which encode a type III secretion system, the intimin adhesin, the translocated intimin receptor (Tir), and other effector proteins. The first gene of LEE1 encodes the Ler regulator, which activates all the other genes within the LEE. We previously reported that the LEE genes were activated by quorum sensing through Ler (V. Sperandio, J. L. Mellies, W. Nguyen, S. Shin, and J. B. Kaper, Proc. Natl. Acad. Sci. USA 96:15196-15201, 1999). In this study we report that a putative regulator in the E. coli genome is itself activated by quorum sensing. This regulator is encoded by open reading frame b3243; belongs to the LysR family of regulators; is present in EHEC, EPEC, and E. coli K-12; and shares homology with the AphB and PtxR regulators of Vibrio cholerae and Pseudomonas aeruginosa, respectively. We confirmed the activation of b3243 by quorum sensing by using transcriptional fusions and renamed this regulator quorum-sensing E. coli regulator A (QseA). We observed that QseA activated transcription of ler and therefore of the other LEE genes. An EHEC qseA mutant had a striking reduction of type III secretion activity, which was complemented when qseA was provided in trans. Similar results were also observed with a qseA mutant of EPEC. The QseA regulator is part of the regulatory cascade that regulates EHEC and EPEC virulence genes by quorum sensing.

scholarly journals Functional Characterization of EscK (Orf4), a Sorting Platform Component of the Enteropathogenic Escherichia coli Injectisome

2016 ◽  
Vol 199 (1) ◽  
Author(s):  
Eduardo Soto ◽  
Norma Espinosa ◽  
Miguel Díaz-Guerrero ◽  
Meztlli O. Gaytán ◽  
José L. Puente ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Type Iii Secretion ◽  
Diarrheal Disease ◽  
Functional Characterization ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Effector Proteins ◽  
Content Type ◽  
Enterocyte Effacement

ABSTRACT The type III secretion system (T3SS) is a supramolecular machine used by many bacterial pathogens to translocate effector proteins directly into the eukaryotic host cell cytoplasm. Enteropathogenic Escherichia coli (EPEC) is an important cause of infantile diarrheal disease in underdeveloped countries. EPEC virulence relies on a T3SS encoded within a chromosomal pathogenicity island known as the locus of enterocyte effacement (LEE). In this work, we pursued the functional characterization of the LEE-encoded protein EscK (previously known as Orf4). We provide evidence indicating that EscK is crucial for efficient T3S and belongs to the SctK (OrgA/YscK/MxiK) protein family, whose members have been implicated in the formation of a sorting platform for secretion of T3S substrates. Bacterial fractionation studies showed that EscK localizes to the inner membrane independently of the presence of any other T3SS component. Combining yeast two-hybrid screening and pulldown assays, we identified an interaction between EscK and the C-ring/sorting platform component EscQ. Site-directed mutagenesis of conserved residues revealed amino acids that are critical for EscK function and for its interaction with EscQ. In addition, we found that T3S substrate overproduction is capable of compensating for the absence of EscK. Overall, our data suggest that EscK is a structural component of the EPEC T3SS sorting platform, playing a central role in the recruitment of T3S substrates for boosting the efficiency of the protein translocation process. IMPORTANCE The type III secretion system (T3SS) is an essential virulence determinant for enteropathogenic Escherichia coli (EPEC) colonization of intestinal epithelial cells. Multiple EPEC effector proteins are injected via the T3SS into enterocyte cells, leading to diarrheal disease. The T3SS is encoded within a genomic pathogenicity island termed the locus of enterocyte effacement (LEE). Here we unravel the function of EscK, a previously uncharacterized LEE-encoded protein. We show that EscK is central for T3SS biogenesis and function. EscK forms a protein complex with EscQ, the main component of the cytoplasmic sorting platform, serving as a docking site for T3S substrates. Our results provide a comprehensive functional analysis of an understudied component of T3SSs.

scholarly journals Type III Secretion-Dependent Sensitivity of Escherichia coli O157 to Specific Ketolides

2015 ◽  
Vol 60 (1) ◽  
pp. 459-470 ◽  
Author(s):  
Romina J. Fernandez-Brando ◽  
Nao Yamaguchi ◽  
Amin Tahoun ◽  
Sean P. McAteer ◽  
Trudi Gillespie ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Type Iii Secretion ◽  
Pathogenic Bacteria ◽  
Bacterial Colonization ◽  
Effector Proteins ◽  
Content Type ◽  
E Coli ◽  
Type Iii ◽  
Bacterial Binding

ABSTRACTA subset of Gram-negative bacterial pathogens uses a type III secretion system (T3SS) to open up a conduit into eukaryotic cells in order to inject effector proteins. These modulate pathways to enhance bacterial colonization. In this study, we screened established bioactive compounds for any that could repress T3SS expression in enterohemorrhagicEscherichia coli(EHEC) O157. The ketolides telithromycin and, subsequently, solithromycin both demonstrated repressive effects on expression of the bacterial T3SS at sub-MICs, leading to significant reductions in bacterial binding and actin-rich pedestal formation on epithelial cells. Preincubation of epithelial cells with solithromycin resulted in significantly less attachment ofE. coliO157. Moreover, bacteria expressing the T3SS were more susceptible to solithromycin, and there was significant preferential killing ofE. coliO157 bacteria when they were added to epithelial cells that had been preexposed to the ketolide. This killing was dependent on expression of the T3SS. Taken together, this research indicates that the ketolide that has accumulated in epithelial cells may traffic back into the bacteria via the T3SS. Considering that neither ketolide induces the SOS response, nontoxic members of this class of antibiotics, such as solithromycin, should be considered for future testing and trials evaluating their use for treatment of EHEC infections. These antibiotics may also have broader significance for treating infections caused by other pathogenic bacteria, including intracellular bacteria, that express a T3SS.

scholarly journals Regulators Encoded in the Escherichia coli Type III Secretion System 2 Gene Cluster Influence Expression of Genes within the Locus for Enterocyte Effacement in Enterohemorrhagic E. coli O157:H7

2004 ◽  
Vol 72 (12) ◽  
pp. 7282-7293 ◽  
Author(s):  
Lihong Zhang ◽  
Roy R. Chaudhuri ◽  
Chrystala Constantinidou ◽  
Jon L. Hobman ◽  
Mala D. Patel ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Gene Cluster ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Regulatory Genes ◽  
E Coli ◽  
Type Iii ◽  
System 2 ◽  
Enterocyte Effacement

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) O157:H7 subverts host cells through a type III secretion system encoded by the locus for enterocyte effacement (LEE). Genome sequencing of this pathotype revealed the existence of a gene cluster encoding components of a second cryptic type III secretion system, E. coli type III secretion system 2 (ETT2). Recently, we showed that the ETT2 gene cluster is present in whole or in part in the majority of E. coli strains but is unable to encode a functional secretion system in most strains, including EHEC O157:H7. However, here we show that mutational inhibition of two regulatory genes (ECs3720 or etrA and ECs3734 or eivF) from the ETT2 cluster in EHEC O157:H7 leads to greatly increased secretion of proteins encoded by the LEE and to increased adhesion to human intestinal cells. Studies in which transcriptional fusions and microarrays were used indicated that EtrA and EivF exert profound negative effects on gene transcription within the LEE. Consistent with these observations, expression of these regulators in an EHEC O26:H- strain led to suppression of protein secretion under LEE-inducing conditions. These findings provide fresh examples of the influence of mobile genetic elements on regulation of the LEE and of cross talk between type III secretion system gene clusters. In addition, they provide a cautionary tale because they show that the effects of regulatory genes can outlive widespread decay of other genes in a functionally coherent gene cluster, a phenomenon that we have named the “Cheshire cat effect.” It also seems likely that variations in the ETT2 regulator repertoire might account for strain-to-strain variation in secretion of LEE-encoded proteins.

scholarly journals α1-Antitrypsin Binds to and Interferes with Functionality of EspB from Atypical and Typical Enteropathogenic Escherichia coli Strains

2004 ◽  
Vol 72 (8) ◽  
pp. 4344-4350 ◽  
Author(s):  
Sabine Knappstein ◽  
Tina Ide ◽  
M. Alexander Schmidt ◽  
Gerhard Heusipp
Keyword(s):  
Escherichia Coli ◽  
Host Cell ◽  
Type Iii Secretion ◽  
Pore Formation ◽  
Effector Proteins ◽  
Dependent Manner ◽  
E Coli ◽  
Binding Partner ◽  
Type Iii ◽  
Cell Defense

ABSTRACT Enteropathogenic Escherichia coli (EPEC), including diffusely adhering atypical E. coli, strains use a type III secretion system to deliver effector proteins into the membrane and cytoplasm of infected cells. The E. coli secreted proteins A, B, and D (EspA, EspB, and EspD) are required for the formation of the characteristic attaching and effacing (A/E) lesions. EspB and EspD are thought to form a translocation pore in the host cell membrane through which effector proteins are injected into the host cytosol. Besides its function in pore formation, EspB has been found in the cytosol and implicated to function as an effector protein. We screened for putative host cell proteins interacting with EspB of atypical EPEC strains and identified α1-antitrypsin (AAT) as a binding partner for EspB. AAT binds to EspB in pull-down and overlay experiments and also to EspD in overlay experiments. In agreement with the role of EspB and EspD in pore formation, EPEC-mediated hemolysis of red blood cells is strongly reduced by AAT in a concentration-dependent manner, indicating that AAT interferes with type III secretion by inhibiting the formation of the translocation pore. This is further supported by a decreased actin polymerization after infection of HeLa or CaCo-2 cells with EPEC in the presence of physiologically relevant concentrations of AAT. In this study, we identify AAT as a new binding partner for EspB and EspD, suggesting a previously unappreciated role for AAT in host cell defense against EPEC infections and potentially also against other bacterial pathogens.

scholarly journals Comparative Analysis of Locus of Enterocyte Effacement Pathogenicity Islands of Atypical Enteropathogenic Escherichia coli

2004 ◽  
Vol 72 (11) ◽  
pp. 6722-6728 ◽  
Author(s):  
Julia F. Gärtner ◽  
M. Alexander Schmidt
Keyword(s):  
Escherichia Coli ◽  
Type Iii Secretion ◽  
Functional Expression ◽  
Secretion System ◽  
Effector Proteins ◽  
Eukaryotic Cells ◽  
Pathogenicity Islands ◽  
E Coli ◽  
Enterocyte Effacement ◽  
Pedestal Formation

ABSTRACT The pathogenicity of enteropathogenic Escherichia coli (EPEC) is linked to the locus of enterocyte effacement, or LEE, encoding a type III secretion system (T3SS) that directly transfers bacterial effector proteins into eukaryotic cells. Atypical diffusely adhering EPEC (DA-EPEC) strains that harbor homologues of the LEE but lack the EPEC adherence factor plasmid have been increasingly associated with outbreaks of diarrhea. In this study, we have completely sequenced and functionally characterized LEE pathogenicity islands derived from the clinical DA-EPEC isolates 3431 (O8:H−) and 0181 (O119:H9:K61). LEE3431 and LEE0181 exhibit genetic organization analogous to that of the prototype LEEE2348/69. Genes constituting the T3SS apparatus are highly conserved. However, LEE-encoded effector proteins exhibit major differences. Transfer and functional expression of LEE0181 in an E. coli XL1 blue MR background demonstrated that LEE0181 contains all the information for signal transduction and pedestal formation.

scholarly journals espC Pathogenicity Island of Enteropathogenic Escherichia coli Encodes an Enterotoxin

2001 ◽  
Vol 69 (1) ◽  
pp. 315-324 ◽  
Author(s):  
Jay L. Mellies ◽  
Fernando Navarro-Garcia ◽  
Iruka Okeke ◽  
Julie Frederickson ◽  
James P. Nataro ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Developing Countries ◽  
Type Iii Secretion ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Pathogenicity Island ◽  
Enteropathogenic Escherichia Coli ◽  
Ussing Chambers ◽  
E Coli ◽  
Enterocyte Effacement

ABSTRACT At least five proteins are secreted extracellularly by enteropathogenic Escherichia coli (EPEC), a leading cause of infant diarrhea in developing countries. However only one, EspC, is known to be secreted independently of the type III secretion apparatus encoded by genes located within the 35.6-kb locus of enterocyte effacement pathogenicity island. EspC is a member of the autotransporter family of proteins, and the secreted portion of the molecule is 110 kDa. Here we determine that the espC gene is located within a second EPEC pathogenicity island at 60 min on the chromosome of E. coli. We also show that EspC is an enterotoxin, indicated by rises in short-circuit current and potential difference in rat jejunal tissue mounted in Ussing chambers. In addition, preincubation with antiserum against the homologous Pet enterotoxin of enteroaggregative E. coli eliminated EspC enterotoxin activity. Like the EAF plasmid, the espCpathogenicity island was found only in a subset of EPEC, suggesting that EspC may play a role as an accessory virulence factor in some but not all EPEC strains.

Probiotics Slow the Growth of Pathogenic Bacteria

2019 ◽  
Vol 14 (1) ◽  
pp. 28-31 ◽  
Author(s):  
Rowles H. L.
Keyword(s):  
Growth Rate ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Diarrheal Disease ◽  
Growth Curves ◽  
Mortality Rates ◽  
Controlled Delivery ◽  
E Coli ◽  
Multiple Strains ◽  
Commercial Probiotics

Probiotics are live microorganisms, which when ingested in sufficient amounts, confer health benefits to the host by improving the gut microflora balance. The purpose of this research was to determine whether commercial probiotic products containing multitude of commensal bacteria would reduce the growth rate of pathogenic bacteria, specifically Escherichia coli and Salmonella typhimurium. Growth curves were established, and the growth rates were compared for samples of E. coli, S. typhimurium, Nature’s Bounty Controlled Delivery probiotic, Sundown Naturals Probiotic Balance probiotic, and cocultures of the pathogenic bacteria mixed with the probiotics. The findings of this research were that the commercial probiotics significantly reduced the growth rate of E. coli and S. typhimurium when combined in cocultures. Probiotics containing multiple strains may be taken prophylactically to reduce the risk of bacterial infections caused by E. coli and S. typhimurium. Probiotics could be used to reduce the high global morbidity and mortality rates of diarrheal disease.

Pollution, Toxicity and Carcinogenicity of Organic Dyes and their Catalytic Bio-Remediation

2019 ◽  
Vol 25 (34) ◽  
pp. 3645-3663 ◽  
Author(s):  
Muhammad Ismail ◽  
Kalsoom Akhtar ◽  
M.I. Khan ◽  
Tahseen Kamal ◽  
Murad A. Khan ◽  
...  
Keyword(s):  
Water Pollution ◽  
Textile Industry ◽  
Pathogenic Bacteria ◽  
Diarrheal Disease ◽  
Organic Dyes ◽  
Chemical Reduction ◽  
Cost Effective ◽  
Agricultural Runoff ◽  
E Coli ◽  
Sanitation Services

: Water pollution due to waste effluents of the textile industry is seriously causing various health problems in humans. Water pollution with pathogenic bacteria, especially Escherichia coli (E. coli) and other microbes is due to the mixing of fecal material with drinking water, industrial and domestic sewage, pasture and agricultural runoff. Among the chemical pollutants, organic dyes due to toxic nature, are one of the major contaminants of industrial wastewater. Adequate sanitation services and drinking quality water would eliminate 200 million cases of diarrhea, which results in 2.1 million less deaths caused by diarrheal disease due to E. coli each year. Nanotechnology is an excellent platform as compared to conventional treatment methods of water treatment and remediation from microorganisms and organic dyes. In the current study, toxicity and carcinogenicity of the organic dyes have been studied as well as the remediation/inactivation of dyes and microorganism has been discussed. Remediation by biological, physical and chemical methods has been reviewed critically. A physical process like adsorption is cost-effective, but can’t degrade dyes. Biological methods were considered to be ecofriendly and cost-effective. Microbiological degradation of dyes is cost-effective, eco-friendly and alternative to the chemical reduction. Besides, certain enzymes especially horseradish peroxidase are used as versatile catalysts in a number of industrial processes. Moreover, this document has been prepared by gathering recent research works related to the dyes and microbial pollution elimination from water sources by using heterogeneous photocatalysts, metal nanoparticles catalysts, metal oxides and enzymes.

scholarly journals High-density transposon libraries utilising outward-oriented promoters identify mechanisms of action and resistance to antimicrobials

2020 ◽  
Vol 367 (22) ◽  
Author(s):  
Chris Coward ◽  
Gopujara Dharmalingham ◽  
Omar Abdulle ◽  
Tim Avis ◽  
Stephan Beisken ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Selective Advantage ◽  
Mechanisms Of Action ◽  
Over Expression ◽  
E Coli ◽  
Synthase Inhibitor ◽  
Established Technique ◽  
Bacterial Transposon

ABSTRACT The use of bacterial transposon mutant libraries in phenotypic screens is a well-established technique for determining which genes are essential or advantageous for growth in conditions of interest. Standard, inactivating, transposon libraries cannot give direct information about genes whose over-expression gives a selective advantage. We report the development of a system wherein outward-oriented promoters are included in mini-transposons, generation of transposon mutant libraries in Escherichia coli and Pseudomonas aeruginosa and their use to probe genes important for growth under selection with the antimicrobial fosfomycin, and a recently-developed leucyl-tRNA synthase inhibitor. In addition to the identification of known mechanisms of action and resistance, we identify the carbon–phosphorous lyase complex as a potential resistance liability for fosfomycin in E. coli and P. aeruginosa. The use of this technology can facilitate the development of novel mechanism-of-action antimicrobials that are urgently required to combat the increasing threat worldwide from antimicrobial-resistant pathogenic bacteria.

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