scholarly journals Prevention and Cure of Systemic Escherichia coli K1 Infection by Modification of the Bacterial Phenotype

2004 ◽  
Vol 48 (5) ◽  
pp. 1503-1508 ◽  
Author(s):  
Naseem Mushtaq ◽  
Maria B. Redpath ◽  
J. Paul Luzio ◽  
Peter W. Taylor
Keyword(s):  
Escherichia Coli ◽  
Capsular Polysaccharide ◽  
Virulent Strain ◽  
Polysialic Acid ◽  
Intraperitoneal Administration ◽  
Systemic Infection ◽  
E Coli ◽  
Inhibition Of Growth ◽  
Old Rats ◽  
Prevention And Cure

ABSTRACT Escherichia coli is a common cause of meningitis and sepsis in the newborn infant, and the large majority of isolates from these infections produce a polysialic acid (PSA) capsular polysaccharide, the K1 antigen, that protects the bacterial cell from immune attack. We determined whether a capsule-depolymerizing enzyme, by removing this protective barrier, could alter the outcome of systemic infection in an animal model. Bacteriophage-derived endosialidase E (endoE) selectively degrades the PSA capsule on the surface of E. coli K1 strains. Intraperitoneal administration of small quantities of recombinant endoE (20 μg) to 3-day-old rats, colonized with a virulent strain of K1, prevented bacteremia and death from systemic infection. The enzyme had no effect on the viability of E. coli strains but sensitized strains expressing PSA to killing by the complement system. This study demonstrates the potential therapeutic efficacy of agents that cure infections by modification of the bacterial phenotype rather than by killing or inhibition of growth of the pathogen.

scholarly journals Administration of capsule-selective endosialidase E minimizes upregulation of organ gene expression induced by experimental systemic infection with Escherichia coli K1

Microbiology ◽  
2010 ◽  
Vol 156 (7) ◽  
pp. 2205-2215 ◽  
Author(s):  
Andrea Zelmer ◽  
Melissa J. Martin ◽  
Ozan Gundogdu ◽  
George Birchenough ◽  
Rebecca Lever ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Stress Responses ◽  
Polysialic Acid ◽  
Newborn Infants ◽  
Systemic Infection ◽  
Bacterial Invasion ◽  
Neonatal Rats ◽  
Bacterial Surface ◽  
E Coli

Many neurotropic strains of Escherichia coli cause potentially lethal bacteraemia and meningitis in newborn infants by virtue of their capacity to elaborate the protective polysialic acid (polySia) K1 capsule. Recombinant capsule depolymerase, endosialidase E (endoE), selectively removes polySia from the bacterial surface; when administered intraperitoneally to infected neonatal rats, the enzyme interrupts the transit of E. coli K1 from gut to brain via the blood circulation and prevents death from systemic infection. We now show that experimental E. coli K1 infection is accompanied by extensive modulation of host gene expression in the liver, spleen and brain tissues of neonatal rats. Bacterial invasion of the brain resulted in a threefold or greater upregulation of approximately 400 genes, a large number of which were associated with the induction of inflammation and the immune and stress responses: these included genes encoding C–X–C and C–C chemokines, lipocalins, cytokines, apolipoproteins and enzymes involved in the synthesis of low-molecular-mass inflammatory mediators. Administration of a single dose of endoE, 24 h after initiation of systemic infection, markedly reduced, but did not completely abrogate, these changes in gene expression, suggesting that attenuation of E. coli K1 virulence by removal of the polySia capsule may minimize the attendant inflammatory processes that contribute to poor outcome in these severe systemic infections.

scholarly journals The Genotoxin Colibactin Is a Determinant of Virulence in Escherichia coli K1 Experimental Neonatal Systemic Infection

2015 ◽  
Vol 83 (9) ◽  
pp. 3704-3711 ◽  
Author(s):  
Alex J. McCarthy ◽  
Patricia Martin ◽  
Emilie Cloup ◽  
Richard A. Stabler ◽  
Eric Oswald ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Gastrointestinal Tract ◽  
Virulent Strain ◽  
Systemic Infection ◽  
Double Strand Breaks ◽  
Neonatal Rat ◽  
Very High Frequency ◽  
Content Type ◽  
Strand Breaks ◽  
E Coli

Escherichia colistrains expressing the K1 capsule are a major cause of sepsis and meningitis in human neonates. The development of these diseases is dependent on the expression of a range of virulence factors, many of which remain uncharacterized. Here, we show that all but 1 of 34E. coliK1 neonatal isolates carriedclbAandclbP, genes contained within thepkspathogenicity island and required for the synthesis of colibactin, a polyketide-peptide genotoxin that causes genomic instability in eukaryotic cells by induction of double-strand breaks in DNA. Inactivation ofclbAandclbPinE. coliA192PP, a virulent strain of serotype O18:K1 that colonizes the gastrointestinal tract and translocates to the blood compartment with very high frequency in experimental infection of the neonatal rat, significantly reduced the capacity of A192PP to colonize the gut, engender double-strand breaks in DNA, and cause invasive, lethal disease. Mutation ofclbA, which encodes a pleiotropic enzyme also involved in siderophore synthesis, impacted virulence to a greater extent than mutation ofclbP, encoding an enzyme specific to colibactin synthesis. Restoration of colibactin gene function by complementation reestablished the fully virulent phenotype. We conclude that colibactin contributes to the capacity ofE. coliK1 to colonize the neonatal gastrointestinal tract and to cause invasive disease in the susceptible neonate.

scholarly journals Genome evolution and the emergence of pathogenicity in avian Escherichia coli

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Leonardos Mageiros ◽  
Guillaume Méric ◽  
Sion C. Bayliss ◽  
Johan Pensar ◽  
Ben Pascoe ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Association Studies ◽  
Virulence Gene ◽  
Systemic Infection ◽  
Disease Status ◽  
Evolutionary Mechanisms ◽  
Sustainable Food ◽  
E Coli ◽  
Common Birds ◽  
Systemic Infections

AbstractChickens are the most common birds on Earth and colibacillosis is among the most common diseases affecting them. This major threat to animal welfare and safe sustainable food production is difficult to combat because the etiological agent, avian pathogenic Escherichia coli (APEC), emerges from ubiquitous commensal gut bacteria, with no single virulence gene present in all disease-causing isolates. Here, we address the underlying evolutionary mechanisms of extraintestinal spread and systemic infection in poultry. Combining population scale comparative genomics and pangenome-wide association studies, we compare E. coli from commensal carriage and systemic infections. We identify phylogroup-specific and species-wide genetic elements that are enriched in APEC, including pathogenicity-associated variation in 143 genes that have diverse functions, including genes involved in metabolism, lipopolysaccharide synthesis, heat shock response, antimicrobial resistance and toxicity. We find that horizontal gene transfer spreads pathogenicity elements, allowing divergent clones to cause infection. Finally, a Random Forest model prediction of disease status (carriage vs. disease) identifies pathogenic strains in the emergent ST-117 poultry-associated lineage with 73% accuracy, demonstrating the potential for early identification of emergent APEC in healthy flocks.

Serological and conformational properties of E. coli K92 capsular polysaccharide and its N-propionylated derivative both illustrate that induced antibody does not recognize extended epitopes of polysialic acid: Implications for a comprehensive conjugate vaccine against groups B and C N. meningitidis

2002 ◽  
Vol 80 (8) ◽  
pp. 1055-1063 ◽  
Author(s):  
Robert A Pon ◽  
Nam Huan Khieu ◽  
Qing-Ling Yang ◽  
Jean-Robert Brisson ◽  
Harold J Jennings
Keyword(s):  
Molecular Dynamics ◽  
Immune Response ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Competitive Inhibition ◽  
Polysialic Acid ◽  
E Coli ◽  
Protective Epitope ◽  
Conformational Properties ◽  
Group B

The capsular polysaccharide of E. coli K92 (K92P) contains elements in common with the capsular polysaccharides of both groups B and C N. meningitidis, and may therefore form the basis of a bivalent vaccine. In an attempt to augment the cross-protective immune response to group B meningococci, the N-acetyl groups of the K92P were replaced by N-propionyl groups (NPrK92P) and conjugated to protein. This strategy had previously been applied with success to the poorly immunogenic capsular polysaccharide of group B meningococcus (GBMP), and the bactericidal epitope was found to be exclusively mimicked by extended helical segments of the NPrGBMP. The NPrK92P-conjugate, in relation to a K92P-conjugate, failed to enhance the response to GBMP but did generate a measurable response to NPrGBMP, but only at the expense of a greatly reduced GCMP response. Despite the presence of an immune response to NPrGBMP, the anti-NPrK92 serum was not bactericidal. Competitive inhibition studies with NPrGBMP oligosaccharides suggested the NPrK92 antibodies could not cross-react with the protective epitope on group B meningococci, as defined by extended helical segments of the NPrGBMP, but only recognized short non-bactericidal NPrGBMP epitopes. This hypothesis was supported from the conformational and molecular dynamics studies of the K92P, which demonstrated a lack of extended conformations that resemble the GBMP extended epitope. Indeed, the conformational properties of the K92P more closely resembled those of the GCMP, thereby explaining the observed moderate cross-protection of the K92P antiserum towards group C meningococci. Thus, on the basis of these results, it can be concluded that K92P, regardless of N-propionyl modification, will not serve as an effective single vaccine component against both groups B and C meningococci.Key words: conjugate vaccine, Neisseria meningitidis, polysialic acid, NMR, molecular dynamics.

scholarly journals Biosynthesis of heparin. Use of Escherichia coli K5 capsular polysaccharide as a model substrate in enzymic polymer-modification reactions

1991 ◽  
Vol 275 (1) ◽  
pp. 151-158 ◽  
Author(s):  
M Kusche ◽  
H H Hannesson ◽  
U Lindahl
Keyword(s):  
Escherichia Coli ◽  
Structural Analysis ◽  
Binding Sites ◽  
Proteinase Inhibitor ◽  
Capsular Polysaccharide ◽  
Polymer Modification ◽  
Sulphated Polysaccharide ◽  
E Coli ◽  
High Affinity ◽  
K5 Polysaccharide

A capsular polysaccharide from Escherichia coli K5 was previously found to have the same structure, [-(4)beta GlcA(1)→(4)alpha GlcNAc(1)-]n, as that of the non-sulphated precursor polysaccharide in heparin biosynthesis [Vann, Schmidt, Jann & Jann (1981) Eur. J. Biochem. 116, 359-364]. The K5 polysaccharide was N-deacetylated (by hydrazinolysis) and N-sulphated, and was then incubated with detergent-solubilized enzymes from a heparin-producing mouse mastocytoma, in the presence of adenosine 3′-phosphate 5′-phospho[35S] sulphate ([35S]PAPS). Structural analysis of the resulting 35S-labelled polysaccharide revealed the formation of all the major disaccharide units found in heparin. The identification of 2-O-[35S]sulphated IdoA (L-iduronic acid) as well as 6-O-[35S]sulphated GlcNSO3 units demonstrated that the modified K5 polysaccharide served as a substrate in the hexuronosyl C-5-epimerase and the major O-sulphotransferase reactions involved in the biosynthesis of heparin. The GlcA units of the native (N-acetylated) E. coli polysaccharide were attacked by the epimerase only when PAPS was present in the incubations, whereas those of the chemically N-sulphated polysaccharide were epimerized also in the absence of PAPS, in accord with the notion that N-sulphate groups are required for epimerization. With increasing concentrations of PAPS, the mono-O-sulphated disaccharide unit-IdoA(2-OSO3)-GlcNSO3- was progressively converted into the di-O-sulphated species -IdoA(2-OSO3)-GlcNSO3(6-OSO3)-. A small proportion of the 35S-labelled polysaccharide was found to bind with high affinity to the proteinase inhibitor antithrombin. This proportion increased with increasing concentration of PAPS up to a level corresponding to approximately 1-2% of the total incorporated 35S. The solubilized enzymes thus catalysed all the reactions required for the generation of functional antithrombin-binding sites.

Viability of Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in Yellow Fat Spreads as Affected by Storage Temperature

2003 ◽  
Vol 66 (4) ◽  
pp. 549-558 ◽  
Author(s):  
SARAH L. HOLLIDAY ◽  
LARRY R. BEUCHAT
Keyword(s):  
Escherichia Coli ◽  
Listeria Monocytogenes ◽  
Storage Temperature ◽  
Salt Content ◽  
Inactivation Kinetics ◽  
Escherichia Coli O157 ◽  
E Coli ◽  
Inhibition Of Growth ◽  
Time Required ◽  
Kinetics Of

A study was conducted to characterize the survival and inactivation kinetics of a five-serotype mixture of Salmonella (6.23 to 6.55 log10 CFU per 3.5-ml or 4-g sample), a five-strain mixture of Escherichia coli O157:H7 (5.36 to 6.14 log10 CFU per 3.5-ml or 4-g sample), and a six-strain mixture of Listeria monocytogenes (5.91 to 6.18 log10 CFU per 3.5-ml or 4-g sample) inoculated into seven yellow fat spreads (one margarine, one butter-margarine blend, and five dairy and nondairy spreads and toppings) after formulation and processing and stored at 4.4, 10, and 21°C for up to 94 days. Neither Salmonella nor E. coli O157:H7 grew in any of the test products. The time required for the elimination of each pathogen depended on the product and the storage temperature. Death was more rapid at 21°C than at 4.4 or 10°C. Depending on the product, the time required for the elimination of viable cells at 21°C ranged from 5 to 7 days to >94 days for Salmonella, from 3 to 5 days to 28 to 42 days for E. coli O157:H7, and from 10 to 14 days to >94 days for L. monocytogenes. Death was most rapid in a water-continuous spray product (pH 3.66, 4.12% salt) and least rapid in a butter-margarine blend (pH 6.66, 1.88% salt). E. coli O157:H7 died more rapidly than did Salmonella or L. monocytogenes regardless of storage temperature. Salmonella survived longer in high-fat (≥61%) products than in products with lower fat contents. The inhibition of growth is attributed to factors such as acidic pH, salt content, the presence of preservatives, emulsion characteristics, and nutrient deprivation. L. monocytogenes did not grow in six of the test products, but its population increased between 42 and 63 days in a butter-margarine blend stored at 10°C and between 3 and 7 days when the blend was stored at 21°C. On the basis of the experimental parameters examined in this study, traditional margarine and spreads not containing butter are not “potentially hazardous foods” in that they do not support the growth of Salmonella, E. coli O157:H7, or L. monocytogenes.

scholarly journals Polysialic and colanic acids metabolism in Escherichia coli K92 is regulated by RcsA and RcsB

2013 ◽  
Vol 33 (3) ◽  
Author(s):  
Nicolás Navasa ◽  
Leandro Rodríguez-Aparicio ◽  
Miguel Ángel Ferrero ◽  
Andrea Monteagudo-Mera ◽  
Honorina Martínez-Blanco
Keyword(s):  
Escherichia Coli ◽  
Low Temperatures ◽  
Regulatory Mechanism ◽  
Polysialic Acid ◽  
Negative Regulators ◽  
Surface Appearance ◽  
E Coli ◽  
Colanic Acid

We have shown previously that Escherichia coli K92 produces two different capsular polymers known as CA (colanic acid) and PA (polysialic acid) in a thermoregulated manner. The complex Rcs phosphorelay is largely related to the regulation of CA synthesis. Through deletion of rscA and rscB genes, we show that the Rcs system is involved in the regulation of both CA and PA synthesis in E. coli K92. Deletion of either rcsA or rcsB genes resulted in decreased expression of cps (CA biosynthesis cluster) at 19°C and 37°C, but only CA production was reduced at 19°C. Concerning PA, both deletions enhanced its synthesis at 37°C, which does not correlate with the reduced kps (PA biosynthesis cluster) expression observed in the rcsB mutant. Under this condition, expression of the nan operon responsible for PA catabolism was greatly reduced. Although RcsA and RcsB acted as negative regulators of PA synthesis at 37°C, their absence did not reestablish PA expression at low temperatures, despite the deletion of rcsB resulting in enhanced kps expression. Finally, our results revealed that RcsB controlled the expression of several genes (dsrA, rfaH, h-ns and slyA) involved in the thermoregulation of CA and PA synthesis, indicating that RcsB is part of a complex regulatory mechanism governing the surface appearance in E. coli.

scholarly journals Insight Into the Virulence Related Secretion Systems, Fimbriae, and Toxins in O2:K1 Escherichia coli Isolated From Bovine Mastitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Min Sun ◽  
Xing Gao ◽  
Kejie Zhao ◽  
Jiale Ma ◽  
Huochun Yao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bovine Mastitis ◽  
Systemic Infection ◽  
Infection Model ◽  
Secretion Systems ◽  
E Coli ◽  
Bacterial Pathogenicity ◽  
Mouse Infection Model ◽  
Type Iv ◽  
Mouse Infection

Mastitis remains a major infection of dairy cows and an important issue for the dairy farmers, and Escherichia coli (E. coli) bovine mastitis is a disease of significant economic importance in the dairy industry. Our study identified six isolates belong to phylogroup B2 from 69 bovine mastitis E. coli strains. Except for one serotype O1 strain, all group B2 isolates were identified into serotype O2 and showed significantly higher mortality in the mouse infection than other phylogroups' strains. Genomic analyses and further tests were performed to examine the role of secretion systems, fimbriae, and toxins during the systemic infection of O2:K1 strain BCE049. Two integral T6SS loci and three predicted effectors clusters were found to assemble the functional T6SS complex and deliver diverse toxic effectors to modulate bacterial virulence in the mouse infection model. A total of four T4SS loci were harbored in the BCE049 genome, three of them are encoded in different plasmids, respectively, whereas the last one locates within the bacterial chromosome at FQU84_16715 to FQU84_16760, and was significantly involved in the bacterial pathogenicity. Numerous predicted pilus biosynthesis gene loci were found in the BCE049 genome, whereas most of them lost long fragments encoding key genes for the pili assembly. Unexpectedly, a type IV pilus gene locus locating at FQU84_01405 to FQU84_01335 in the plasmid 2, was found to be required for the full virulence of mastitis strain BCE049. It should be noted that a genetic neighborhood inserted with diverse genes is encoded by the plasmid 1, which harbors three prominent toxins including β-hemolysin, cytotoxic necrotizing factor 2 and cytolethal distending toxin type III. Consequent studies verified that these toxins significantly contributed to the bacterial pathogenicity. These findings provide a molecular blueprint for understanding the underlying mechanisms employed by the bovine mastitis E. coli to colonize in host and cause systemic infection.

scholarly journals Uji Antibakteri Nanopartikel Kitosan terhadap Pertumbuhan Bakteri Staphylococcus aureus dan Escherichia coli. (Antibacterial Test of Chitosan Nanoparticles against Staphylococcus Aureus and Escherichia coli)

2020 ◽  
Vol 10 (1) ◽  
pp. 7
Author(s):  
Alce Magani ◽  
Trina Tallei ◽  
Beivy Kolondam
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Chitosan Nanoparticles ◽  
Inhibition Zone ◽  
Antibacterial Test ◽  
E Coli ◽  
Inhibition Of Growth ◽  
Significant Difference ◽  
One Way Anova

Uji Antibakteri Nanopartikel Kitosan terhadap Pertumbuhan Bakteri Staphylococcus aureus dan Escherichia coli.(Antibacterial Test of Chitosan Nanoparticles against Staphylococcus Aureus and Escherichia coli) Alce K. Magani*, Trina E. Tallei, Beivy J. KolondamProgram Studi Biologi, FMIPA Universitas Sam Ratulangi, Manado 95115*Email korespondensi: [email protected] (Article History: Received 30-12-2019; Revised 15-01-2020; Accepted 23-01-2020) Abstrak Antibakteri merupakan zat yang dapat menghambat pertumbuhan bakteri dan dapat membunuh bakteri penyebab infeksi. Staphylococcus aureus dan Escherichia coli merupakan bakteri Gram positif dan Gram negatif yang dapat menimbulkan infeksi atau penyakit dalam tubuh. Penelitian ini bertujuan untuk menguji aktivitas bakteri patogen dengan memakai nanopartikel kitosan sebagai antibakteri yang dibuat dalam empat konsentrasi (0,5%, 1%, 1,5% dan 2%) serta penggunaan kontrol asam asetat 1%, ciprofloxacin dan air steril sebagai pembanding. Metode penelitian yang digunakan yaitu metode gelasi ionik untuk pembuatan nanopartikel kitosan dan difusi agar untuk pengujian antibakteri. Data dianalisis dengan One Way Anova yang dilanjutkan dengan metode BNT (Beda Nyata Terkecil). Hasil penelitian diperoleh penghambatan pertumbuhan bakteri S. aureus dan E. coli tertinggi pada konsentrasi 0,5%, dengan diameter zona hambat hari pertama sampai hari ketiga 12,31 mm, 9,98 mm, dan 20,46 mm pada S. aureus dan 15,88 mm, 18,71 mm, dan 20,43 mm pada E. coli, kategori kuat, dan bersifat bakteriostatik dan penghambatan terendah pada konsentrasi 2% dengan diameter zona hambat pada S. aureus yaitu 5,56 mm, 5,50 mm, dan 5,40 mm, dan pada E. coli yaitu 5,93 mm, 9,64 mm, dan 12,58 mm, kategori sedang, dan bersifat bakteriostatik. Kata kunci: Kitosan, nanopartikel kitosan, aktivitas antibakteri.  Abstract Antibacteria is a substance that can inhibit the growth of bacteria and able to kill bacteria that cause infections. Staphylococcus aureus and Escherichia coli are Gram positive and Gram negative bacteria that able to cause infections or diseases. This study aimed to examine the activity of pathogenic bacteria by using chitosan nanoparticles as antibacterial. The treatments were made in four concentrations (0.5%, 1%, 1.5% and 2%) and, for comparison, there were also acetic acid control, ciprofloxacin and sterile water. The research method used is the ionic gelation method for the manufacture of chitosan nanoparticles and agar diffusion for antibacterial testing. Data were analyzed with One Way Anova followed by LSD (Least Significant Difference) method. The results showed the highest inhibition of growth of S. aureus and E. coli bacteria at a concentration of 0.5%, with a diameter of inhibition zones of the first day to the third day of 12.31 mm, 9.98 mm, and 20.46 mm in S. aureus and 15,88 mm, 18,71 mm, and 20,43 mm in E. coli, the strong category, and are bacteriostatic and the lowest inhibition was at 2% concentration with inhibition zone diameters in S. aureus namely 5.568 mm, 5.50 mm, and 5, 40 mm, and in E. coli, 5.93 mm, 9.63 mm and 12.58 mm, the medium category and bacteriostatic.Key words: Chitosan, nanoparticles chitosan, antibacterial activity.

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