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Mark Shepherd, Maud E S Achard, Adi Idris, Makrina Totsika, Minh-Duy Phan, Kate M Peters, Sohinee Sarkar, Cláudia A Ribeiro, Louise V Holyoake, Dimitrios Ladakis, Glen C Ulett, Matthew J Sweet, Robert K Poole, Alastair G McEwan, Mark A Schembri
Nitric oxide (NO) is a toxic free radical produced by neutrophils and macrophages in response to infection. Uropathogenic Escherichia coli (UPEC) induces a variety of defence mechanisms in response to NO, including direct NO detoxification (Hmp, NorVW, NrfA), iron-sulphur cluster repair (YtfE), and the expression of the NO-tolerant cytochrome bd-I respiratory oxidase (CydAB). The current study quantifies the relative contribution of these systems to UPEC growth and survival during infection. Loss of the flavohemoglobin Hmp and cytochrome bd-I elicit the greatest sensitivity to NO-mediated growth inhibition, whereas all but the periplasmic nitrite reductase NrfA provide protection against neutrophil killing and promote survival within activated macrophages...
October 21, 2016: Scientific Reports
Birong Li, Babitha Haridas, Ashley R Jackson, Hanna Cortado, Nicholas Mayne, Rebecca Kohnken, Brad Bolon, Kirk M McHugh, Andrew L Schwaderer, John D Spencer, Christina B Ching, David S Hains, Sheryl S Justice, Santiago Partida-Sanchez, Brian Becknell
Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis...
October 19, 2016: American Journal of Physiology. Renal Physiology
Shu-Cheng Liu, Xiao-Min Han, Ming Shi, Zi-Li Pang
This study aimed to provide evidence of persistent uropathogenic Escherichia coli (UPEC) in female patients with recurrent urinary tract infection (UTI) after antibiotic therapy. We collected biopsies of the bladder, and clean-catch urine samples from 32 women who had episodes of recurrent UTI and were given antibiotic therapy. Urine samples and biopsies were analyzed by conventional bacteriological techniques. Phylogenetic group and 16 virulence factors (VFs) of UPEC were determined using polymerase chain reaction (PCR)...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Santosh Kumar Singh, Seema Kumari, Minakshi Gupta
Escherichia coli mediated urinary tract infection has been reported to be most prevalent among patients of different class, gender and ages. Currently, multidrug resistant E. coli harboring several virulence factors are most perilous threats for patients especially for elders. The aim of this study was to determine the antibiotic resistance pattern, co-resistance and phenotypic virulence factors present in uropathogenic E. coli isolates from aged patients. Thirty-nine E. coli isolates were collected during May-June 2014 from patients aged 50-80 years...
October 12, 2016: Microbial Pathogenesis
Renata Yakubov, Machiel van den Akker, Kaba Machamad, Amit Hochberg, Erez Nadir, Adi Klein
BACKGROUND: Empiric antibiotic treatment of urinary tract infection (UTI) in children relies on surveillance data about epidemiology and resistance patterns of common uropathogens. METHODS: A retrospective analysis of bacteria isolated from urine cultures of children with febrile UTI, seen at the pediatric department of a large regional hospital (Hillel-Yaffe Medical Center, Hadera, Israel) between January 2007 and December 2014. RESULTS: In this study period, 829 positive urine cultures were analyzed...
October 12, 2016: Pediatric Infectious Disease Journal
Christina M Beck, Julia L E Willett, David A Cunningham, Jeff J Kim, David A Low, Christopher S Hayes
Many Gram-negative bacterial pathogens express contact-dependent growth inhibition (CDI) systems that promote cell-cell interaction. CDI+ bacteria express surface CdiA effector proteins, which transfer their C-terminal toxin domains into susceptible target cells upon binding to specific receptors. CDI+ cells also produce immunity proteins that neutralize the toxin domains delivered from neighboring siblings. Here, we show that CdiAEC536 from uropathogenic Escherichia coli 536 (EC536) uses OmpC and OmpF as receptors to recognize target bacteria...
October 2016: PLoS Pathogens
Krzysztof Mikołajczyk, Radosław Kaczmarek, Marcin Czerwiński
Transcription factor EKLF (Erythroid Krüppel-Like Factor) belongs to the group of Krüppellike factors, which regulate proliferation, differentiation, development and apoptosis of mammalian cells. EKLF factor is present in erythroid cells, where it participates in regulation of hematopoiesis, expression of genes encoding transmembrane proteins (including blood group antigens), and heme biosynthesis enzymes. It is also a key factor in downregulation of γ-globins and activation of β-globin gene expression...
October 6, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Dominika Drzewiecka, Gabriela Lewandowska
Urinary tract infections (UTIs) pose a threat especially to women, the individuals with weakened immunity or with abnormalities in the urinary tract as well as to hospitalized and catheterized patients. The bacteria from the genus Proteus, especially P. mirabilis, are important UTI pathogenic factors. They frequently cause chronic, recurrent or severely complicated infections, resulting in the urinary stones production due to urease and other virulence factors. The ability to survive inside the stones and the increasing antibiotic resistance make it difficult to eradicate the bacteria from the urinary tract...
September 30, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Matthieu Rousseau, H M Sharon Goh, Sarah Holec, Matthew L Albert, Rohan B H Williams, Molly A Ingersoll, Kimberly A Kline
Catheter-associated urinary tract infections (CAUTI) are the most common hospital-associated infections. Here, we report that bladder catheterization initiated a persistent sterile inflammatory reaction within minutes of catheter implantation. Catheterization resulted in increased expression of genes associated with defense responses and cellular migration, with ensuing rapid and sustained innate immune cell infiltration into the bladder. Catheterization also resulted in hypersensitivity to Enterococcus faecalis and uropathogenic Escherichia coli (UPEC) infection, in which colonization was achieved using an inoculum 100-fold lower than the ID90 for infection of an undamaged urothelium with the same uropathogens...
September 22, 2016: JCI Insight
Vittorio Magri, Emanuele Montanari, Emanuela Marras, Gianpaolo Perletti
Although fluoroquinolones are first-line agents for the treatment of National Institutes of Health (NIH) category II chronic bacterial prostatitis (CBP), therapy with these agents is not always feasible due to the increasing worldwide resistance of causative uropathogens. New therapeutic options are urgently required, as drugs such as β-lactam antibiotics distribute poorly to prostatic sites of infection and trimethoprim therapy is often unfeasible due to high resistance rates. The present study aimed to analyze the efficacy of aminoglycosides, administered to a cohort of 78 patients affected by fluoroquinolone-resistant CBP, or excluded from fluoroquinolone therapy due to various contraindications...
October 2016: Experimental and Therapeutic Medicine
David A Hufnagel, Margery L Evans, Sarah E Greene, Jerry S Pinkner, Scott J Hultgren, Matthew R Chapman
The extracellular matrix protects Escherichia coli from immune cells, oxidative stress, predation, and other environmental stresses. Production of the E. coli extracellular matrix is regulated by transcription factors that are tuned to environmental conditions. The biofilm master-regulator protein CsgD upregulates curli and cellulose, the two major polymers in the extracellular matrix of uropathogenic E. coli (UPEC) biofilms. Here, we found that cAMP regulates curli, cellulose, and UPEC biofilms through csgD The alarmone cAMP is produced by adenylate cyclase (CyaA) and deletion of cyaA resulted in lower extracellular matrix production and biofilm formation...
October 3, 2016: Journal of Bacteriology
Lisa K McLellan, David A Hunstad
The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities...
September 27, 2016: Trends in Molecular Medicine
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
Jérôme Tourret, Benjamin P Willing, Sara Dion, Jayden MacPherson, Erick Denamur, Brett B Finlay
BACKGROUND: Transplant recipients are treated with immunosuppressive (IS) therapies, which impact host-microbial interactions. We examined the impact of IS drugs on gut microbiota and on the expression of ileal antimicrobial peptides. METHODS: Mice were treated for 14 days with prednisolone, mycophenolate mofetil, tacrolimus, a combination of these 3 drugs, everolimus or water. Faeces were collected before and after treatment initiation. Ileal samples were collected after sacrifice...
September 27, 2016: Transplantation
Klaus Deckmann, Wolfgang Kummer
A peculiar cell type of the respiratory and gastrointestinal epithelia, originally termed "brush cell" or "tuft cell" by electron microscopists because of its apical tuft of microvilli, utilizes the canonical bitter taste transduction cascade known from oropharyngeal taste buds to detect potential hazardous compounds, e.g. bacterial products. Upon stimulation, this cell initiates protective reflexes and local inflammatory responses through release of acetylcholine and chemokines. Guided by the understanding of these cells as sentinels, they have been newly discovered at previously unrecognized anatomical locations, including the urethra...
September 29, 2016: Histochemistry and Cell Biology
Akhilesh K Chaurasia, Nanasaheb D Thorat, Anshula Tandon, Jin-Hahn Kim, Sung Ha Park, Kyeong Kyu Kim
Antibiotic resistant bacteria not only affect human health and but also threatens the safety in hospitals and among communities. However, the emergence of drug resistant bacteria is inevitable due to evolutionary selection as a consequence of indiscriminate antibiotic usage. Therefore, it is necessary to develop a novel strategy by which pathogenic bacteria can be eliminated without triggering resistance. We propose a novel magnetic nanoparticle-based physical treatment against pathogenic bacteria, which blocks biofilm formation and kills bacteria...
September 27, 2016: Scientific Reports
Matt S Conover, Ségolène Ruer, Joemar Taganna, Vasilios Kalas, Henri De Greve, Jerome S Pinkner, Karen W Dodson, Han Remaut, Scott J Hultgren
Uropathogenic E. coli (UPEC) is the dominant cause of urinary tract infections, clinically described as cystitis. UPEC express CUP pili, which are extracellular fibers tipped with adhesins that bind mucosal surfaces of the urinary tract. Here we identify the role of the F9/Yde/Fml pilus for UPEC persistence in the inflamed urothelium. The Fml adhesin FmlH binds galactose β1-3 N-acetylgalactosamine found in core-1 and -2 O-glycans. Deletion of fmlH had no effect on UPEC virulence in an acute mouse model of cystitis...
October 12, 2016: Cell Host & Microbe
Chee Wei Tan, Maciej Piotr Chlebicki
A urinary tract infection (UTI) is a collective term for infections that involve any part of the urinary tract. It is one of the most common infections in local primary care. The incidence of UTIs in adult males aged under 50 years is low, with adult women being 30 times more likely than men to develop a UTI. Appropriate classification of UTI into simple or complicated forms guides its management and the ORENUC classification can be used. Diagnosis of a UTI is based on a focused history, with appropriate investigations depending on individual risk factors...
September 2016: Singapore Medical Journal
Cátia Marques, Luís Telo Gama, Adriana Belas, Karin Bergström, Stéphanie Beurlet, Alexandra Briend-Marchal, Els M Broens, Marta Costa, Delphine Criel, Peter Damborg, Marloes A M van Dijk, Astrid M van Dongen, Roswitha Dorsch, Carmen Martin Espada, Bernhard Gerber, Maria Kritsepi-Konstantinou, Igor Loncaric, Domenico Mion, Dusan Misic, Rebeca Movilla, Gudrun Overesch, Vincent Perreten, Xavier Roura, Joachim Steenbergen, Dorina Timofte, Georg Wolf, Renato Giulio Zanoni, Sarah Schmitt, Luca Guardabassi, Constança Pomba
BACKGROUND: There is a growing concern regarding the increase of antimicrobial resistant bacteria in companion animals. Yet, there are no studies comparing the resistance levels of these organisms in European countries. The aim of this study was to investigate geographical and temporal trends of antimicrobial resistant bacteria causing urinary tract infection (UTI) in companion animals in Europe. The antimicrobial susceptibility of 22 256 bacteria isolated from dogs and cats with UTI was determined...
2016: BMC Veterinary Research
E M Galván, C Mateyca, L Ielpi
Most catheter-associated urinary tract infections are polymicrobial. Here, uropathogen interactions in dual-species biofilms were studied. The dual-species associations selected based on their prevalence in clinical settings were Klebsiella pneumoniae-Escherichia coli, E. coli-Enterococcus faecalis, K. pneumoniae-E. faecalis, and K. pneumoniae-Proteus mirabilis. All species developed single-species biofilms in artificial urine. The ability of K. pneumoniae to form biofilms was not affected by E. coli or E. faecalis co-inoculation, but was impaired by P...
October 2016: Biofouling
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