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Justin J J van der Hooft, Robert J Goldstone, Susan Harris, Karl E V Burgess, David G E Smith
Since its first isolation a century ago, the gut inhabitant Escherichia coli strain Nissle 1917 has been shown to have probiotic activities; however, it is yet not fully elucidated which differential factors play key roles in its beneficial interactions with the host. To date, no metabolomics studies have been reported investigating the potential role of small molecules in functional strain differentiation of Nissle from its genetically close neighbors. Here, we present results of liquid chromatography coupled to high-resolution mass spectrometry characterization of extracellular metabolomes of E...
2019: Frontiers in Microbiology
Valerie P O'Brien, Denise A Dorsey, Thomas J Hannan, Scott J Hultgren
Urinary tract infections (UTI) are extremely common and can be highly recurrent, with 1-2% of women suffering from six or more recurrent episodes per year. The high incidence of recurrent UTI, including recurrent infections caused by the same bacterial strain that caused the first infection, suggests that at least some women do not mount a protective adaptive immune response to UTI. Here we observed in a mouse model of cystitis (bladder infection) that infection with two different clinical uropathogenic Escherichia coli (UPEC) isolates, UTI89 or CFT073, resulted in different kinetics of bacterial clearance and different susceptibility to same-strain recurrent infection...
December 2018: PLoS Pathogens
Birte Scharf, Jandirk Sendker, Ulrich Dobrindt, Andreas Hensel
LC-MS characterized cranberry extract from the fruits of Vaccinium macrocarpon inhibited under in vitro conditions the bacterial adhesion of Escherichia coli strain 2980 uropathogenic E. coli (UPEC strains UTI89, NU14) to T24 bladder cells and adhesion of UPEC strain CFT073 to A498 kidney cells in a concentration-dependent manner. Within a biomedical study, urine samples from 16 volunteers (8 male, 8 female) consuming cranberry extract for 7 d (900 mg/d) were analyzed for potential antiadhesive activity against UPEC by ex vivo experiments...
October 12, 2018: Planta Medica
Courtney L Luterbach, Harry L T Mobley
The MarR-like protein PapX represses the transcription of the flagellar master regulator genes flhDC in uropathogenic Escherichia coli (UPEC), the primary cause of uncomplicated urinary tract infections (UTIs). PapX is encoded by the pap operon, which also encodes the adherence factors termed P fimbriae. Both adherence and motility are critical for productive colonization of the urinary tract. However, the mechanisms involved in coordinating the transition between adherence and motility are not well characterized...
December 2018: Infection and Immunity
Hongxia Niu, Rebecca Yee, Peng Cui, Shuo Zhang, Lili Tian, Wanliang Shi, David Sullivan, Bingdong Zhu, Wenhong Zhang, Ying Zhang
BACKGROUND: Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infections (UTIs). Due to increasing antibiotic-resistance among UPEC bacteria, new treatment options for UTIs are urgently needed. OBJECTIVE: To identify new agents targeting growing bacteria that may be used for the treatment of antibiotic-resistant UTIs. METHOD: We screened a clinical compound library consisting of 1,524 compounds using a high throughput 96-well plate assay and ranked the activities of the selected agents according to their MICs against the UPEC strain UTI89...
August 7, 2018: Current Drug Discovery Technologies
E J Battaglioli, K G K Goh, T S Atruktsang, K Schwartz, M A Schembri, R A Welch
Uropathogenic Escherichia coli (UPEC) is the most common etiologic agent of uncomplicated urinary tract infection (UTI). An important mechanism of gene regulation in UPEC is phase variation that involves inversion of a promoter-containing DNA element via enzymatic activity of tyrosine recombinases, resulting in biphasic, ON or OFF expression of target genes. The UPEC reference strain CFT073 has five tyrosine site-specific recombinases that function at two previously characterized promoter inversion systems, fimS and hyxS Three of the five recombinases are located proximally to their cognate target elements, which is typical of promoter inversion systems...
August 7, 2018: MBio
M Berleur, F Guérin, L Massias, F Chau, J Poujade, V Cattoir, B Fantin, V de Lastours
Background: Alternative therapeutic regimens are urgently needed against carbapenemase-producing Enterobacteriaceae. Fosfomycin often remains active against KPC and OXA-48 producers, but emergence of resistance is a major limitation. Our aim was to determine whether the association of temocillin with fosfomycin might be useful to treat KPC- or OXA-48-producing Escherichia coli infections. Methods: Isogenic derivatives of E. coli CFT073 with blaKPC-3- or blaOXA-48-harbouring plasmids (named CFT073-KPC-3 and CFT073-OXA-48, respectively) were used...
August 3, 2018: Journal of Antimicrobial Chemotherapy
M Goswami, F A Khan, A Ibrisevic, P-E Olsson, J Jass
AIMS: The impact of municipal waste on pathogenic micro-organisms released into the environment is a public health concern. This study aims to evaluate the effects of sewage sludge and antibiotic contaminants on stress response, virulence and antibiotic resistance in a pathogenic Escherichia coli. METHODS AND RESULTS: The effects of sewage sludge leachates on uropathogenic E. coli CFT073 were determined by monitoring the expression of 45 genes associated with antibiotic/metal resistance, stress response and virulence using RT-qPCR...
June 21, 2018: Journal of Applied Microbiology
Bindu Subhadra, Dong Ho Kim, Jaeseok Kim, Kyungho Woo, Kyung Mok Sohn, Hwa-Jung Kim, Kyudong Han, Man Hwan Oh, Chul Hee Choi
Urinary tract infections (UTIs) are among the most common infections in humans, predominantly caused by uropathogenic Escherichia coli (UPEC). The diverse genomes of UPEC strains mostly impede disease prevention and control measures. In this study, we comparatively analyzed the whole genome sequence of a highly virulent UPEC strain, namely UPEC 26-1, which was isolated from urine sample of a patient suffering from UTI in Korea. Whole genome analysis showed that the genome consists of one circular chromosome of 5,329,753 bp, comprising 5064 protein-coding genes, 122 RNA genes (94 tRNA, 22 rRNA and 6 ncRNA genes), and 100 pseudogenes, with an average G+C content of 50...
June 2018: Genes & Genomics
Courtney L Luterbach, Valerie S Forsyth, Michael D Engstrom, Harry L T Mobley
Uropathogenic Escherichia coli strains utilize a variety of adherence factors that assist in colonization of the host urinary tract. TosA (<u>t</u>ype <u>o</u>ne <u>s</u>ecretion <u>A</u>) is a nonfimbrial adhesin that is predominately expressed during murine urinary tract infection (UTI), binds to kidney epithelial cells, and promotes survival during invasive infections. The tosRCBDAEF operon encodes the secretory machinery necessary for TosA localization to the E...
May 2018: MSphere
Ambika M V Murthy, Minh-Duy Phan, Kate M Peters, Nguyen Thi Khanh Nhu, Rodney A Welch, Glen C Ulett, Mark A Schembri, Matthew J Sweet
Uropathogenic E. coli (UPEC) causes the majority of urinary tract infections (UTIs), which are a major global public health concern. UPEC uses numerous mechanisms to subvert the innate immune system, including targeting macrophage functions. We recently showed that some UPEC strains rapidly kill human macrophages via an NLRP3-independent pathway, and also trigger NLRP3-dependent IL-1β processing. In this study, we used random transposon mutagenesis in the reference strain CFT073 to identify UPEC genes that mediate human macrophage cell death...
December 31, 2018: Virulence
Isak Demirel, Alexander Persson, Annelie Brauner, Eva Särndahl, Robert Kruse, Katarina Persson
The NLRP3 inflammasome and IL-1β release have recently been suggested to be important for the progression of urinary tract infection (UTI). However, much is still unknown regarding the interaction of UPEC and the NLRP3 inflammasome. The purpose of this study was to elucidate what virulence factors uropathogenic Escherichia coli (UPEC) use to modulate NLRP3 inflammasome activation and subsequent IL-1β release and the role of NLRP3 for UPEC colonization of bladder epithelial cells. The bladder epithelial cell line 5637, CRISPR/Cas9 generated NLRP3, caspase-1 and mesotrypsin deficient cell lines and transformed primary bladder epithelial cells (HBLAK) were stimulated with UPEC isolates and the non-pathogenic MG1655 strain...
2018: Frontiers in Cellular and Infection Microbiology
Wilma Neumann, Martina Sassone-Corsi, Manuela Raffatellu, Elizabeth M Nolan
Enteric Gram-negative bacteria, including Escherichia coli, biosynthesize and deploy the triscatecholate siderophore enterobactin (Ent) in the vertebrate host to acquire iron, an essential nutrient. We report that Ent-Cipro, a synthetic siderophore-antibiotic conjugate based on the native Ent platform that harbors an alkyl linker at one of the catechols with a ciprofloxacin cargo attached, affords targeted antibacterial activity against E. coli strains that express the pathogen-associated iroA gene cluster...
April 18, 2018: Journal of the American Chemical Society
Alice Chinghsuan Chang, Bernard Haochih Liu
The categorization of microbial strains is conventionally based on the molecular method, and seldom are the morphological characteristics in the bacterial strains studied. In this research, we revealed the macromolecular structures of the bacterial surface via AFM mechanical mapping, whose resolution was not only determined by the nanoscale tip size but also the mechanical properties of the specimen. This technique enabled the nanoscale study of membranous structures of microbial strains with simple specimen preparation and flexible working environments, which overcame the multiple restrictions in electron microscopy and label-enable biochemical analytical methods...
February 2, 2018: Nanoscale Research Letters
Lana Dbeibo, Julia J van Rensburg, Sara N Smith, Kate R Fortney, Dharanesh Gangaiah, Hongyu Gao, Juan Marzoa, Yunlong Liu, Harry L T Mobley, Stanley M Spinola
CpxRA is an envelope stress response system found in all members of the family Enterobacteriaceae ; CpxA has kinase activity for CpxR and phosphatase activity for phospho-CpxR, a transcription factor. CpxR also accepts phosphate groups from acetyl phosphate, a glucose metabolite. Activation of CpxR increases the transcription of genes encoding membrane repair and downregulates virulence determinants. We hypothesized that activation of CpxR could serve as an antimicrobial/antivirulence strategy and discovered compounds that activate CpxR in Escherichia coli by inhibiting CpxA phosphatase activity...
March 2018: Infection and Immunity
Rafael Iriya, Karan Syal, Wenwen Jing, Manni Mo, Hui Yu, Shelley E Haydel, Shaopeng Wang, Nongjian Tao
Diagnosing antibiotic-resistant bacteria currently requires sensitive detection of phenotypic changes associated with antibiotic action on bacteria. Here, we present an optical imaging-based approach to quantify bacterial membrane deformation as a phenotypic feature in real-time with a nanometer scale (∼9  nm) detection limit. Using this approach, we found two types of antibiotic-induced membrane deformations in different bacterial strains: polymyxin B induced relatively uniform spatial deformation of Escherichia coli O157:H7 cells leading to change in cellular volume and ampicillin-induced localized spatial deformation leading to the formation of bulges or protrusions on uropathogenic E...
December 2017: Journal of Biomedical Optics
A Pourbaix, F Guérin, V de Lastours, F Chau, M Auzou, E Boulley, V Cattoir, B Fantin
Prevalence of fosfomycin resistance in E. coli clinical isolates from UTIs remains very low. Our hypothesis was that fosfomycin resistance may be associated with a biological cost. Three groups of strains of E. coli belonging to the B2 phylogenetic group were used: clinical wild-type (WT) isolates, clinical multidrug-resistant isolates and in vitro fosfomycin-resistant derivatives from the uropathogen clinical strain E. coli CFT073. In each group fosfomycin-susceptible and -resistant isolates were compared...
December 2017: International Journal of Medical Microbiology: IJMM
Sébastien Crépin, Gaëlle Porcheron, Sébastien Houle, Josée Harel, Charles M Dozois
The pst gene cluster encodes the phosphate-specific transport (Pst) system. Inactivation of the Pst system constitutively activates the two-component regulatory system PhoBR and attenuates the virulence of pathogenic bacteria. In uropathogenic Escherichia coli strain CFT073, attenuation by inactivation of pst is predominantly attributed to the decreased expression of type 1 fimbriae. However, the molecular mechanisms connecting the Pst system and type 1 fimbriae are unknown. To address this, a transposon library was constructed in the pst mutant, and clones were tested for a regain in type 1 fimbrial production...
December 15, 2017: Journal of Bacteriology
Ased S M Ali, Catherine Mowbray, Marcelo Lanz, Anna Stanton, Samantha Bowen, Claire L Varley, Paul Hilton, Karen Brown, Wendy Robson, Jennifer Southgate, Phillip D Aldridge, Alison Tyson-Capper, Soman Abraham, Robert S Pickard, Judith Hall
The identification of the host defence peptides as target effectors in the innate defence of the uro-genital tract creates new translational possibilities for immunomodulatory therapies, specifically vaginal therapies to treat women suffering from rUTI, particularly those carrying the TLR5_C1174T SNP. Urinary tract infections (UTIs) are a microbial disease reported worldwide. Women are particularly susceptible with many suffering debilitating recurrent (r) infections. Treatment is by antibiotics, but such therapy is linked to antibiotic resistance and re-infection...
September 8, 2017: Scientific Reports
Yujie He, Jie Fang, Chong Zhang, Jun Pan, Qi Jin, Yingzhi Yang, Linyao Wang, Baoming Wang, Dayong Zhang, Jianping Pan
Pyelonephritis is an infection of the upper urinary tract with characteristic histological change to neutrophil infiltration in the kidney. The majority of pyelonephritis is caused by uropathogenic Escherichia (E.) coli (UPEC) bearing distinct virulence factors. Toll/interleukin‑1 receptor domain‑containing protein C (TcpC) encoded by E. coli is an important virulence factor in the majority of strains of UPEC and inhibits macrophage‑mediated innate immunity, which serves an essential role in the pathogenesis of pyelonephritis...
September 2017: Molecular Medicine Reports
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