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Xiangru Wang, Ravi Maruvada, Andrew J Morris, Jun O Liu, Michael J Wolfgang, Dong Jae Baek, Robert Bittman, Kwang Sik Kim
Central nervous system (CNS) infection continues to be an important cause of mortality and morbidity, necessitating new approaches for investigating its pathogenesis, prevention and therapy. Escherichia coli is the most common Gram-negative bacillary organism causing meningitis, which develops following penetration of the blood-brain barrier (BBB). By chemical library screening, we identified epidermal growth factor receptor (EGFR) as a contributor to E. coli invasion of the BBB in vitro. Here, we obtained the direct evidence that CNS-infecting E...
October 2016: PLoS Pathogens
Laurel Mydock-McGrane, Zachary Cusumano, Zhenfu Han, Jana Binkley, Maria Kostakioti, Thomas Hannan, Jerome S Pinkner, Roger Klein, Vasilios Kalas, Jan Crowley, Nigam P Rath, Scott J Hultgren, James W Janetka
Gram-negative uropathogenic Escherichia coli (UPEC) bacteria are a causative pathogen of urinary tract infections (UTIs). Previously developed antivirulence inhibitors of the type 1 pilus adhesin, FimH, demonstrated oral activity in animal models of UTI but were found to have limited compound exposure due to the metabolic instability of the O-glycosidic bond (O-mannosides). Herein, we disclose that compounds having the O-glycosidic bond replaced with carbon linkages had improved stability and inhibitory activity against FimH...
October 14, 2016: Journal of Medicinal Chemistry
Peter N Lipke
The recent article "Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins" by Ielasi et al. describes a new development in microbial carbohydrate analysis [Ielasi FS, Alioscha-Perez M, Donohue D, Claes S, Sahli H, Schols D, Willaert RG, mBio 7(4):e00584-16, 2016,]. Specific carbohydrate ligands have been identified from the patterns of lectin binding to oligosaccharides printed on a chip. The new technique links the output to a comprehensive glycan database and offers a number of data visualization options...
2016: MBio
Mohammad Reza Asadi Karam, Mehri Habibi, Saeid Bouzari
Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) are among the most common infections in human. Antibiotics are common therapy for UTIs, but increase in antibiotic resistance will complicate future treatment of the infections, making the development of an efficacious UTI vaccine more urgent. In this study, we have evaluated intranasally the efficacy of FliC and FimH antigens of UPEC in different vaccine formulations with and without cholera toxin (CT) adjuvant. Immunization of mice with FliC in fusion form or admixed with FimH elicited higher levels of serum, mucosal and cell-mediated responses than FimH alone...
September 2016: Biologicals: Journal of the International Association of Biological Standardization
Francesco S Ielasi, Mitchel Alioscha-Perez, Dagmara Donohue, Sandra Claes, Hichem Sahli, Dominique Schols, Ronnie G Willaert
UNLABELLED: The first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptors of pathogenic adhesins been described. A novel strategy-based on the construction of a lectin-glycan interaction (LGI) network-to identify the potential human binding receptors for pathogenic adhesins with lectin activity was developed...
2016: MBio
Rico Schmidt, Andor Krizsan, Daniela Volke, Daniel Knappe, Ralf Hoffmann
Bacteria have acquired resistance mechanisms to overcome antibiotic treatments, triggering major concerns about the return of epidemic infections. Antimicrobial peptides identified in insects, animals, and plants represent a huge pool of promising lead structures that can be further developed for medical applications. Short proline-rich antimicrobial peptides (PrAMPs) have gained much attention due to their clinically interesting activity spectrum, serum protease stability, efficacy in murine infection models, and low adverse effects...
August 5, 2016: Journal of Proteome Research
Shuai Zhi, Graham Banting, Qiaozhi Li, Thomas A Edge, Edward Topp, Mykola Sokurenko, Candis Scott, Shannon Braithwaite, Norma J Ruecker, Yutaka Yasui, Tim McAllister, Linda Chui, Norman F Neumann
UNLABELLED: Escherichia coli has been proposed to have two habitats-the intestines of mammals/birds and the nonhost environment. Our goal was to assess whether certain strains of E. coli have evolved toward adaptation and survival in wastewater. Raw sewage samples from different treatment plants were subjected to chlorine stress, and ∼59% of the surviving E. coli strains were found to contain a genetic insertion element (IS30) located within the uspC-flhDC intergenic region. The positional location of the IS30 element was not observed across a library of 845 E...
September 15, 2016: Applied and Environmental Microbiology
Xiaolong Yang, Kaihui Sha, Guangya Xu, Hanwen Tian, Xiaoying Wang, Shanze Chen, Yi Wang, Jingyu Li, Junli Chen, Ning Huang
Uropathogenic Escherichia coli (UPEC) biofilm formation enables the organism to avoid the host immune system, resist antibiotics, and provide a reservoir for persistent infection. Once the biofilm is established, eradication of the infection becomes difficult. Therefore, strategies against UPEC biofilm are urgently required. In this study, we investigated the effect of allicin, isolated from garlic essential oil, on UPEC CFT073 and J96 biofilm formation and dispersal, along with its effect on UPEC adhesion ability and swimming motility...
2016: International Journal of Molecular Sciences
Samema Sarowar, Olivia J Hu, Glenn T Werneburg, David G Thanassi, Huilin Li
UNLABELLED: The chaperone/usher pathway is used by Gram-negative bacteria to assemble adhesive surface structures known as pili or fimbriae. Uropathogenic strains of Escherichia coli use this pathway to assemble P and type 1 pili, which facilitate colonization of the kidney and bladder, respectively. Pilus assembly requires a periplasmic chaperone and outer membrane protein termed the usher. The chaperone allows folding of pilus subunits and escorts the subunits to the usher for polymerization into pili and secretion to the cell surface...
September 1, 2016: Journal of Bacteriology
Ingun Lund Witsø, Håkon Valen Rukke, Tore Benneche, Anne Aamdal Scheie
Interference with bacterial quorum sensing communication provides an anti-virulence strategy to control pathogenic bacteria. Here, using the Enteropathogenic E. coli (EPEC) O103:H2, we showed for the first time that thiophenone TF101 reduced expression of lsrB; the gene encoding the AI-2 receptor. Combined results of transcriptional and phenotypic analyses suggested that TF101 interfere with AI-2 signalling, possibly by competing with AI-2 for binding to LsrB. This is supported by in silico docking prediction of thiophenone TF101 in the LsrB pocket...
2016: PloS One
Yi Ren, Agata Palusiak, Wei Wang, Yi Wang, Xiao Li, Huiting Wei, Qingke Kong, Antoni Rozalski, Zhi Yao, Quan Wang
Urinary tract infections (UTIs) are one of the most common bacterial infections in humans, causing cystitis, pyelonephritis, and renal failure. Uropathogenic Escherichia coli (UPEC) is the leading cause of UTIs. Accurate and rapid discrimination of UPEC lineages is useful for epidemiological surveillance. Fimbriae are necessary for the adherence of UPEC strains to host uroepithelia, and seem to be abundant and diverse in UPEC strains. By analyzing all the possible fimbrial operons in UPEC strains, we found that closely related strains had similar types of chaperone-usher fimbriae, and the diversity of fimbrial genes was higher than that of multilocus sequence typing (MLST) genes...
2016: Frontiers in Microbiology
Jerome de Ruyck, Marc F Lensink, Julie Bouckaert
Selective inhibitors of the type 1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against Escherichia coli infections such as urinary-tract infections. To construct these inhibitors, the α-d-mannopyranoside of high-mannose N-glycans, recognized with exclusive specificity on glycoprotein receptors by FimH, forms the basal structure. A hydrophobic aglycon is then linked to the mannose by the O1 oxygen inherently present in the α-anomeric configuration...
May 1, 2016: IUCrJ
Kesavaram Padmavathy, Krishnan Padma, Sikhamani Rajasekaran
Extended Spectrum β-Lactamases (ESBLs) confer resistance to third-generation cephalosporins and CTX-M types have emerged as the most prominent ESBLs worldwide. This study was designed to determine the prevalence of CTX-M positive ESBL-producing urinary E. coli isolates from HIV patients and to establish the association of multidrug resistance, phylogeny, and virulence profile with CTX-M production. A total of 57 ESBL producers identified among 76 E. coli strains isolated from HIV patients from South India were screened for bla CTX-M, AmpC production, multidrug resistance, and nine virulence associated genes (VAGs), fimH, pap, afa/dra, sfa/foc, iutA, fyuA, iroN, usp, and kpsMII...
2016: Journal of Pathogens
Sarah E Graham, Lixin Zhang, Ihsan Ali, Yong Kyun Cho, Miriam D Ismail, Heather A Carlson, Betsy Foxman
A high proportion of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli are of the ST131 lineage, but there are few estimates of ST131 prevalence among ESBL-negative E. coli. Without this information, it is difficult to evaluate the contribution of the ST131 lineage to the emergence and spread of ESBL E. coli. A total of 1658 E. coli isolates were collected at Gachon University Gil Medical Center in Korea from 2006 to 2008. The antibiotic resistance profile was determined for all isolates, and ESBL-positive isolates were screened for the presence of CTX-M-type ESBLs...
July 2016: Infection, Genetics and Evolution
Anis Barati, Aziz Ghaderpour, Li Lee Chew, Chui Wei Bong, Kwai Lin Thong, Ving Ching Chong, Lay Ching Chai
Klebsiella pneumoniae is an opportunistic pathogen that is responsible for causing nosocomial and community-acquired infections. Despite its common presence in soil and aquatic environments, the virulence potential of K. pneumoniae isolates of environmental origin is largely unknown. Hence, in this study, K. pneumoniae isolated from the estuarine waters and sediments of the Matang mangrove estuary were screened for potential virulence characteristics: antibiotic susceptibility, morphotype on Congo red agar, biofilm formation, presence of exopolysaccharide and capsule, possession of virulence genes (fimH, magA, ugE, wabG and rmpA) and their genomic fingerprints...
April 2016: International Journal of Environmental Research and Public Health
Gianluca Interlandi, Wendy E Thomas
The bacterial adhesin FimH consists of an allosterically regulated mannose-binding lectin domain and a covalently linked inhibitory pilin domain. Under normal conditions, the two domains are bound to each other, and FimH interacts weakly with mannose. However, under tensile force, the domains separate and the lectin domain undergoes conformational changes that strengthen its bond with mannose. Comparison of the crystallographic structures of the low and the high affinity state of the lectin domain reveals conformational changes mainly in the regulatory inter-domain region, the mannose binding site and a large β sheet that connects the two distally located regions...
July 2016: Proteins
Laura Iveth Miranda-Estrada, María Ruíz-Rosas, José Molina-López, Isela Parra-Rojas, Edgar González-Villalobos, Natividad Castro-Alarcón
INTRODUCTION: Escherichia coli is the major causative agent of urinary tract infections (UTI), and virulence factors are responsible for the severity of these emerging infections. The aim of this study was to evaluate the relationship between virulence determinants and antibiotic susceptibility with phylogenetic groups of E.coli isolates of UTI in two locations in Mexico. METHODS: An analysis was performed on 50 isolates of E.coli from the centre of the country and 57 from a town in the southwest...
April 2, 2016: Enfermedades Infecciosas y Microbiología Clínica
Sarah L Sutrina, Melanie S J Griffith, Chad Lafeuillee
Escherichia coli strain 15 (ATCC 9723), which forms robust biofilms, was grown under optimal biofilm conditions in NaCl-free Luria-Bertani broth (LB*) or in LB* supplemented with one of the non-metabolizable analogues 2-deoxy-d-glucose (2DG), methyl α-d-mannopyranoside (αMM), or methyl α-d-glucopyranoside (αMG). Biofilm growth was inhibited by mannose analogue 2DG even at very low concentration in unbuffered medium, and the maximal inhibition was enhanced in the presence of either 100 mM KPO4 or 100 mM MOPS, pH 7...
June 2016: Microbiology
T Chalopin, D Alvarez Dorta, A Sivignon, M Caudan, T I Dumych, R O Bilyy, D Deniaud, N Barnich, J Bouckaert, S G Gouin
The anti-adhesive strategy, consisting of disrupting bacterial attachment to the host cells, is widely explored as an alternative to antibiotic therapies. Recently, thiazolylmannosides (TazMans) have been identified as strong anti-adhesives of E. coli strains implied in the gut inflammation of patients with Crohn's disease. In this work, we developed a second generation of TazMans with improved chemical stability. The anomeric nitrogen was substituted by short linkers and the compounds were assessed against the bacterial adhesin FimH and the clinically isolated LF82 E...
April 28, 2016: Organic & Biomolecular Chemistry
Sabine Szunerits, Oleksandr Zagorodko, Virginie Cogez, Tetiana Dumych, Thibaut Chalopin, Dimitri Alvarez Dorta, Adeline Sivignon, Nicolas Barnich, Anne Harduin-Lepers, Iban Larroulet, Aritz Yanguas Serrano, Aloysius Siriwardena, Amaia Pesquera, Amaia Zurutuza, Sébastien G Gouin, Rabah Boukherroub, Julie Bouckaert
Shear force exerted on uropathogenic Escherichia coli adhering to surfaces makes type-1 fimbriae stretch out like springs to catch on to mannosidic receptors. This mechanism is initiated by a disruption of the quaternary interactions between the lectin and the pilin of the two-domain FimH adhesin and transduces allosterically to the mannose-binding pocket of FimH to increase its affinity. Mannose-specific adhesion of 14 E. coli pathovars was measured under flow, using surface plasmon resonance detection on functionalized graphene-coated gold interfaces...
2016: Biology
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