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Bacterial infection

Jan Puetzler, Willem-Jan Metsemakers, Daniel Arens, Stephan Zeiter, Richard Kuehl, Michael J Raschke, Robert Geoff Richards, Thomas Fintan Moriarty
OBJECTIVES: The optimal duration of perioperative antibiotic prophylaxis (PAP) for open fractures remains controversial because of heterogeneous or unclear guidelines and highly variable prophylactic regimens in clinical practice. We aimed at testing different PAP durations under controlled conditions in a contaminated rabbit fracture model. METHODS: A complete humeral osteotomy in 18 rabbits was fixed with a 7-hole locking compression plate and inoculated with Staphylococcus aureus...
April 2018: Journal of Orthopaedic Trauma
Frederick A Rubino, Sujeet Kumar, Natividad Ruiz, Suzanne Walker, Daniel Kahne
MurJ, the flippase that exports the bacterial cell wall mon-omer Lipid II to the periplasm, is a target for new antibiot-ics, which are desperately needed to treat Gram-negative infections. Quantitative methods to monitor MurJ activity are required to characterize inhibitors but are challenging to develop because the lipid-linked substrate is not chemi-cally altered in a flippase reaction. Here we show that MurJ inhibition can be quantified by measuring the accu-mulation of intracellular Lipid II using a biotin-tagging strategy...
March 20, 2018: Journal of the American Chemical Society
Jacqueline M Zaengle-Barone, Abigail C Jackson, David M Besse, Bradford Becken, Mehreen Arshad, Patrick C Seed, Katherine J Franz
The unabated rise in bacterial resistance to conventional antibiotics, coupled with collateral damage to normal flora incurred by overuse of broad-spectrum antibiotics, necessitates the development of new antimicrobials targeted against pathogenic organisms. Here, we explore the antibacterial outcomes and mode of action of a prochelator that exploits the production of β-lactamase enzymes by drug-resistant bacteria to convert a non-toxic compound into a metal-binding antimicrobial agent directly within the microenvironment of pathogenic organisms...
March 20, 2018: ACS Infectious Diseases
Juyoung Yoo, Seung Min Jung, Jason Jungsik Song, Yong-Beom Park, Sang-Won Lee
We investigated the development rate and time, risk factors, predictors, and aetiologies of hospitalised infection in Korean patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively reviewed the medical records of 154 patients with AAV. Hospitalised infection was considered only when patients were admitted for serious infection related to AAV or AAV treatment. The gap-time was defined as the period from diagnosis to the first hospitalised infection or to the last visit for uninfected patients...
March 20, 2018: Clinical Rheumatology
Ivana Mareković, Zrinka Bošnjak, Karla Jurić, Mario Ćorić, Sanja Popović-Grle
Nitroxoline (NTX), 5-nitro-8-hydroxyquinoline is an oral antibiotic with mechanism of bacteriostatic activity that is based on chelation of divalent cations required for bacterial RNA polymerase. Susceptibility to NTX of 100 Escherichia coli urine isolates was determined at the Department of Clinical and Molecular Microbiology, University Hospital Centre Zagreb during September and October 2017. Antimicrobial susceptibility was tested by disc diffusion and the results were interpreted according to the European Committee for Antimicrobial Susceptibility Testing (EUCAST) standards...
March 20, 2018: Journal of Chemotherapy
Elizabeth Ann Misch, Christopher Saddler, James Muse Davis
PURPOSE OF REVIEW: This review describes recent trends in the epidemiology of nontuberculous mycobacteria (NTM), emerging pathogens, new insights into NTM pathogenesis, and advances in diagnosis and treatment. RECENT FINDINGS: Emerging pathogens include Mycobacterium chimaera and drug-resistant subspecies of Mycobacterium abscessus. Important virulence mechanisms of pathogenic NTM include the ability to alter the macrophage's permissiveness to intracellular bacterial growth...
March 19, 2018: Current Infectious Disease Reports
Feng Su, Xin Chen, Xin Liu, Guanghui Liu, Yong Zhang
Bovine tuberculosis is a disease caused by Mycobacterium bovis (M. bovis) that leads to great economic losses in cattle production. The discovery of a reasonable bioagent to reduce M. bovis infection risk and environment contamination becomes significant and urgent. Previous study reported that human β-defensin-3 (HBD3) participated in Mycobacterial immunity and was recognized as a suitable candidate reagent. However, its minimal inhibitory concentration to M. bovis is not yet reported. In this study, we first purified HBD3 protein by recombinant-DNA technology and prokaryotic expression system...
March 20, 2018: AMB Express
Sheela Swamy, William Barcella, Maria De Iorio, Kiren Gill, Rajvinder Khasriya, Anthony S Kupelian, Jennifer L Rohn, James Malone-Lee
PURPOSE: Lower urinary tract symptoms (LUTS) may be associated with chronic urinary tract infection (UTI) undetected by routine diagnostic tests. Antimicrobial therapy might confer benefit for these patients. MATERIALS AND METHODS: Over 10 years, we treated patients with chronic LUTS. Pyuria was adopted as the principal biomarker of infection. Urinary leucocyte counts were recorded from microscopy of fresh midstream urine (MSU) samples. Antibiotics were prescribed and the prescription adjusted to achieve a measurable clinical response and a reduction in pyuria...
March 20, 2018: International Urogynecology Journal
Georgios D Kitsios
Severe bacterial pneumonia is a major global cause of morbidity and mortality, yet current diagnostic approaches rely on identification of causative pathogens by cultures, which require extended incubation periods and often fail to detect relevant pathogens. Consequently, patients are prescribed broad-spectrum antibiotics in a "one-size-fits-all" manner, which may be inappropriate for their individual needs and promote antibiotic resistance. My research focuses on leveraging next-generation sequencing of microbial DNA directly from patient samples for the development of new, culture-independent definitions of pneumonia...
March 2018: MSystems
Tang Gao, Hongliang Zeng, Huan Xu, Feng Gao, Wei Li, Shengwang Zhang, Yi Liu, Guifang Luo, Mingdan Li, Dejian Jiang, Zhigao Chen, Yong Wu, Wei Wang, Wenbin Zeng
Background: Increasing bacterial infections as well as a rise in bacterial resistance call for the development of novel and safe antimicrobial agents without inducing bacterial resistance. Nanoparticles (NPs) present some advantages in treating bacterial infections and provide an alternative strategy to discover new antibiotics. Here, we report the development of novel self-assembled fluorescent organic nanoparticles ( FONs ) with excellent antibacterial efficacy and good biocompatibility. Methods: Self-assembly of 1-(12-(pyridin-1-ium-1-yl)dodecyl)-4-(1,4,5-triphenyl-1H-imidazol-2-yl)pyridin-1-ium (TPIP) in aqueous solution was investigated using dynamic light scattering (DLS) and transmission electron microscopy (TEM)...
2018: Theranostics
Judith A Smith
Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defense against pathogens, but when aberrantly produced, may also drive pathologic inflammation...
2018: Frontiers in Immunology
Gabrielle Bradshaw, Robbie R Lualhati, Cassie L Albury, Neven Maksemous, Deidre Roos-Araujo, Robert A Smith, Miles C Benton, David A Eccles, Rod A Lea, Heidi G Sutherland, Larisa M Haupt, Lyn R Griffiths
Background: We investigated the molecular etiology of a young male proband with confirmed immunodeficiency of unknown cause, presenting with recurrent bacterial and Varicella zoster viral infections in childhood and persistent lymphopenia into early adulthood. Aim: To identify causative functional genetic variants related to an undiagnosed primary immunodeficiency. Method: Whole genome microarray copy number variant (CNV) analysis was performed on the proband followed by whole exome sequencing (WES) and trio analysis of the proband and family members...
2018: Frontiers in Immunology
Alison M Condliffe, Anita Chandra
The activated phosphoinositide 3-kinase δ syndrome (APDS), also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI), is a combined immunodeficiency syndrome caused by gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (encoding p110δ: APDS1 or PASLI-CD) and PIK3R1 (encoding p85α: APDS2 or PASLI-R1). While the disease is clinically heterogeneous, respiratory symptoms and complications are near universal and often severe...
2018: Frontiers in Immunology
Feng Yang, Yonggen Jiang, Lihua Yang, Juanxiu Qin, Mingquan Guo, Yuxia Lu, Hongyou Chen, Yuan Zhuang, Jinghao Zhang, Hong Zhang, Zhaoyun Dai, Min Li, Changqing Yang, Min Chen, Yanmei Zhang, Hu Zhao
Objective: To investigate prevalence of acute diarrhea in Shanghai and analyze virulence associated-genes and antibiotic resistance of major enteropathogens using combination of conventional and molecular epidemiology methods. Method: The 412 stool specimens were obtained by systematic sampling from diarrhea patients throughout entire year 2016. Bacterial and viral pathogens were identified and bacterial isolates were cultured and screened for antibiotic resistance profiles. Two most prevalent bacteria, Vibrio parahaemolyticus and Salmonella were further typed by multi-locus sequence typing (MLST) and analyzed for presence of virulence-associated genes...
2018: Frontiers in Microbiology
Tanzeel Ur Rehman, Arif-Ullah Khan, Azar Abbas, Javid Hussain, Farman Ullah Khan, Kimberly Stieglitz, Shamsher Ali
In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from Nepeta suavis . Nepetolide concentration-dependently (1.0-1000 µg/mL) exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its antioxidant potential, as shown by standard drug, ascorbic acid. It was moderately active against bacterial strain of Staphylococcus aureus . In brine shrimp's lethality model, nepetolide potently showed cytotoxic effect, with LC50 value of 8...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Anne E Clatworthy, Keith P Romano, Deborah T Hung
To date, antibiotics have been identified on the basis of their ability to kill bacteria or inhibit their growth rather than directly for their capacity to improve clinical outcomes of infected patients. Although historically successful, this approach has led to the development of an antibiotic armamentarium that suffers from a number of shortcomings, including the inevitable emergence of resistance and, in certain infections, suboptimal efficacy leading to long treatment durations, infection recurrence, or high mortality and morbidity rates despite apparent bacterial sterilization...
March 19, 2018: Nature Chemical Biology
Tariq A Bhat, Suresh Gopi Kalathil, Paul N Bogner, Austin Miller, Paul V Lehmann, Thomas H Thatcher, Richard P Phipps, Patricia J Sime, Yasmin Thanavala
Despite advocacy to reduce smoking-related diseases, >1 billion people worldwide continue to smoke. Smoking is immunosuppressive and an important etiological factor in the development of several human disorders including respiratory diseases like chronic obstructive pulmonary disease. However, there is a critical gap in the knowledge of the role of secondhand smoke (SHS) in inflammation and immunity. We therefore studied the influence of SHS on pulmonary inflammation and immune responses to respiratory infection by nontypeable Haemophilus influenzae (NTHI) recurrently found in chronic obstructive pulmonary disease patients...
March 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Melinda M Pettigrew, Christian P Ahearn, Janneane F Gent, Yong Kong, Mary C Gallo, James B Munro, Adonis D'Mello, Sanjay Sethi, Hervé Tettelin, Timothy F Murphy
Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Blake Ushijima, Claudia C Häse
Chemotaxis, the directed movement towards or away from a chemical signal, can be essential to bacterial pathogens for locating hosts or avoiding hostile environments. The coral pathogen Vibrio coralliilyticus chemotaxes towards coral mucus; however, chemotaxis has not been experimentally demonstrated to be important for virulence. To further examine this, in-frame mutations were constructed in genes predicted to be important for V. coralliilyticus chemotaxis. Most Vibrio genomes encode multiple homologs of various chemotaxis-related genes and two paralogs of each for cheB , cheR , and cheA were identified...
March 19, 2018: Journal of Bacteriology
Francesca Forti, Dwayne R Roach, Marco Cafora, Maria E Pasini, David S Horner, Ersilia V Fiscarelli, Martina Rossitto, Lisa Cariani, Federica Briani, Laurent Debarbieux, Daniela Ghisotti
The alarming diffusion of multidrug resistant (MDR) bacterial strains requires investigations on non-antibiotic therapies. Amongst them, the use of bacteriophages (phages) as antimicrobial agents, namely phage therapy, is a promising treatment strategy with support by recent successful compassionate treatments in Europe and the U.S.A. In this work, we combined host range and genomic information to design a 6-phage cocktail killing several clinical strains of P. aeruginosa , including those collected from Italian cystic fibrosis (CF) patients, and analyzed the cocktail performance...
March 19, 2018: Antimicrobial Agents and Chemotherapy
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