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Ross D Blundell, Simon J Williams, Samantha D M Arras, Jessica L Chitty, Kirsten L Blake, Daniel J Ericsson, Nidhi Tibrewal, Jurgen Rohr, Y Q Andre E Koh, Ulrike Kappler, Avril A B Robertson, Mark S Butler, Matthew A Cooper, Bostjan Kobe, James A Fraser
Opportunistic fungal pathogens such as Cryptococcus neoformans are a growing cause of morbidity and mortality among immunocompromised populations worldwide. To address the current paucity of antifungal therapeutic agents, further research into fungal-specific drug targets is required. Adenylosuccinate synthetase (AdSS) is a crucial enzyme in the adeosine triphosphate (ATP) biosynthetic pathway, catalyzing the formation of adenylosuccinate from inosine monophosphate and aspartate. We have investigated the potential of this enzyme as an antifungal drug target, finding that loss of function results in adenine auxotrophy in C...
September 9, 2016: ACS Infectious Diseases
Pooja Gopal, Michelle Yee, Jickky Sarathy, Jian Liang Low, Jansy P Sarathy, Firat Kaya, Véronique Dartois, Martin Gengenbacher, Thomas Dick
Pyrazinamide (PZA) is a critical component of first- and second-line treatments of tuberculosis (TB), yet its mechanism of action largely remains an enigma. We carried out a genetic screen to isolate Mycobacterium bovis BCG mutants resistant to pyrazinoic acid (POA), the bioactive derivative of PZA, followed by whole genome sequencing of 26 POA resistant strains. Rather than finding mutations in the proposed candidate targets fatty acid synthase I and ribosomal protein S1, we found resistance conferring mutations in two pathways: missense mutations in aspartate decarboxylase panD, involved in the synthesis of the essential acyl carrier coenzyme A (CoA), and frameshift mutations in the vitro nonessential polyketide synthase genes mas and ppsA-E, involved in the synthesis of the virulence factor phthiocerol dimycocerosate (PDIM)...
September 9, 2016: ACS Infectious Diseases
S S Garcia, Q Du, H Wu
The oral cavity is a dynamic environment characterized by hundreds of bacterial species, saliva, and an influx of nutrients and metal ions such as copper. Although there is a physiologic level of copper in the saliva, the oral cavity is often challenged with an influx of copper ions. At high concentrations copper is toxic and must therefore be strictly regulated by pathogens for them to persist and cause disease. The cariogenic pathogen Streptococcus mutans manages excess copper using the copYAZ operon that encodes a negative DNA-binding repressor (CopY), the P1-ATPase copper exporter (CopA), and the copper chaperone (CopZ)...
December 21, 2015: Molecular Oral Microbiology
Mariaconcetta Varano, Marco Gaspari, Angela Quirino, Giovanni Cuda, Maria Carla Liberto, Alfredo Focà
Ochrobactrum anthropi is a gram-negative rod belonging to the Brucellaceae family, able to colonize a variety of environments, and actually reported as a human opportunistic pathogen. Despite its low virulence, the bacterium causes a growing number of hospital-acquired infections mainly, but not exclusively, in immunocompromised patients. The aim of this study was to obtain an overview of the global proteome changes occurring in O. anthropi in response to different growth temperatures, in order to achieve a major understanding of the mechanisms by which the bacterium adapts to different habitats and to identify some potential virulence factors...
October 18, 2016: Proteomics
Luisa F Castiblanco, George W Sundin
Bacterial biofilms are multicellular aggregates encased in an extracellular matrix mainly composed of exopolysaccharides (EPSs), protein, and nucleic acids, which determines the architecture of the biofilm. Erwinia amylovora Ea1189 forms a biofilm inside the xylem of its host, that results in vessel plugging and water transport impairment. Production of the EPSs amylovoran and levan are critical for the formation of a mature biofilm. Additionally, cyclic dimeric GMP (c-di-GMP) was reported to positively regulate amylovoran biosynthesis and biofilm formation in E...
October 18, 2016: Molecular Plant Pathology
J A DE Fuentes-Vicente, M Cabrera-Bravo, J N Enríquez-Vara, M I Bucio-Torres, A E Gutiérrez-Cabrera, D G Vidal-López, J A Martínez-Ibarra, P M Salazar-Schettino, A Córdoba-Aguilar
Little is known about how the virulence of a human pathogen varies in the environment it shares with its vector. This study focused on whether the virulence of Trypanosoma cruzi (Trypanosomatida: Trypanosomatidae), the causal agent of Chagas' disease, is related to altitude. Accordingly, Triatoma dimidiata (Hemiptera: Reduviidae) specimens were collected at three different altitudes (300, 700 and 1400 m a.s.l.) in Chiapas, Mexico. The parasite was then isolated to infect uninfected T. dimidiata from the same altitudes, as well as female CD-1 mice...
October 18, 2016: Medical and Veterinary Entomology
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
H J Zhang, L N Liu, C Zhang, Y Y Shi, S G Ding
OBJECTIVE: To establish a Mongolian gerbils model by long-term infection of Helicobacter pylori (Hp) with highly-expressed thioredoxin-1 (Trx1) gene and to investigate the histopathological findings of gastric mucosa in Mongolian gerbils. METHODS: In this study, 75 healthy male Mongolian gerbils were randomly divided into 3 groups: Hp with highly-expressed Trx1 gene group (n=30), Hp with lowly-expressed Trx1 gene group (n=30), and control group (n=15). The animals underwent gastric perfusion of Hp suspension once a week for 5 weeks...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Li Zhong, Li Gao, Yongzhen Liu, Kai Li, Miao Wang, Xiaole Qi, Yulong Gao, Xiaomei Wang
Avian reovirus (ARV) infections characterised by severe arthritis, tenosynovitis, pericarditis, and depressed growth have become increasingly frequent in recent years. In this study, we isolated and identified 11 ARV field strains from chickens with viral arthritis and reduced growth in northern China. Comparative analysis of the σC nucleotide and amino acid sequences demonstrated that all isolates, except LN05 and JS01, were closely related to ARV S1133 and clustered in the first genetic lineage. LN05 and JS01 strains were clustered in the third lineage with the ARV 138 strain...
October 18, 2016: Scientific Reports
MyungHee Ku, Yong-Un Baek, Min-Kyu Kwak, Sa-Ouk Kang
BACKGROUND: Glutathione reductase maintains the glutathione level in a reduced state. As previously demonstrated, glutathione is required for cell growth/division and its biosynthesizing-enzyme deficiency causes methylglyoxal accumulation. However, experimental evidences for reciprocal relationships between Cph1-/Efg1-mediated signaling pathway regulation and methylglyoxal production exerted by glutathione reductase on yeast morphology remain unclear. METHODS: Glutathione reductase (GLR1) disruption/overexpression were performed to investigate aspects of pathological/morphological alterations in Candida albicans...
October 14, 2016: Biochimica et Biophysica Acta
Colin M Venner, Immaculate Nankya, Fred Kyeyune, Korey Demers, Cynthia Kwok, Pai-Lien Chen, Sandra Rwambuya, Marshall Munjoma, Tsungai Chipato, Josaphat Byamugisha, Barbara Van Der Pol, Peter Mugyenyi, Robert A Salata, Charles S Morrison, Eric J Arts
INTRODUCTION: Long-term natural history cohorts of HIV-1 in the absence of treatment provide the best measure of virulence by different viral subtypes. METHODS: Newly HIV infected Ugandan and Zimbabwean women (N=303) were recruited and monitored for clinical, social, behavioral, immunological and viral parameters for 3 to 9.5years. RESULTS: Ugandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D (GEE model, P<0...
October 12, 2016: EBioMedicine
Paul J Planet, Apurva Narechania, Liang Chen, Barun Mathema, Sam Boundy, Gordon Archer, Barry Kreiswirth
A deluge of whole-genome sequencing has begun to give insights into the patterns and processes of microbial evolution, but genome sequences have accrued in a haphazard manner, with biased sampling of natural variation that is driven largely by medical and epidemiological priorities. For instance, there is a strong bias for sequencing epidemic lineages of methicillin-resistant Staphylococcus aureus (MRSA) over sensitive isolates (methicillin-sensitive S. aureus: MSSA). As more diverse genomes are sequenced the emerging picture is of a highly subdivided species with a handful of relatively clonal groups (complexes) that, at any given moment, dominate in particular geographical regions...
October 14, 2016: Trends in Microbiology
Aitor Nogales, Kai Huang, Caroline Chauché, Marta L DeDiego, Pablo R Murcia, Colin R Parrish, Luis Martínez-Sobrido
Canine Influenza Virus (CIV) H3N8 is the causative agent of canine influenza, a common and contagious respiratory disease of dogs. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV H3N8. However, live-attenuated influenza vaccines (LAIVs) are known to provide better immunogenicity and protection efficacy than IIVs. Influenza NS1 is a virulence factor that offers an attractive target for the preparation of attenuated viruses as LAIVs. Here we generated recombinant H3N8 CIVs containing truncated or a deleted NS1 protein to test their potential as LAIVs...
October 14, 2016: Virology
Yin Song, Bart P H J Thomma
Verticillium wilt, caused by soil-borne fungi of the genus Verticillium, is an economically important disease that affects a wide range of host plants. Unfortunately, host resistance against Verticillium wilts is not available for many plant species, and the disease is notoriously difficult to combat. Host-induced gene silencing (HIGS) is an RNA interference (RNAi) based process in which small RNAs are produced by the host plant to target parasite transcripts. HIGS has emerged as a promising strategy for improving plant resistance against pathogens by silencing genes that are essential for these pathogens...
October 17, 2016: Molecular Plant Pathology
Xiayan Pan, Jian Wu, Shu Xu, Yabing Duan, Zhou Mingguo
Rice bacterial leaf blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), and rice bacterial leaf streak, caused by Xanthomonas oryzae pv. oryzicola (Xoc), are major diseases of rice. Phenazine-1-carboxylic acid (PCA) is a natural product that is isolated from Pseudomonas spp. and is used to control many important rice diseases in China. We previously reported that PCA disturbs the redox balance, which results in the accumulation of reactive oxygen species (ROS) in Xoo. In this study, we found that PCA significantly up-regulated the transcript levels of catB and katE, which encode catalases, and that PCA-sensitivity was reduced when Xoo and Xoc were cultured with exogenous catalase...
October 17, 2016: Phytopathology
Mai Yamamoto, Takashige Kashimoto, Yukihiro Yoshimura, Nao Tachibana, Shiho Kuroda, Yoshiko Miki, Sou Kitabayashi, Ping Tong, Jianbo Xiao, Koichi Tanaka, Hiroshi Hamamoto, Kazuhisa Sekimizu, Koichiro Yamamoto
The halophilic marine bacterium, Vibrio vulnificus, occasionally causes fatal septicemia in immunocompromised patients. Mice are commonly used as experimental animals to investigate the virulence of V. vulnificus, however, a large number of mice are generally required for bioassays. The present study examined whether the invertebrate species, silkworms, can be used instead of mice to investigate V. vulnificus virulence. When the silkworms were inoculated with 1.2x107 colony forming units of V. vulnificus OPU1‑Rf, a virulent strain of V...
September 26, 2016: Molecular Medicine Reports
Shuai-Yin Chen, Rong-Guang Zhang, Guang-Cai Duan
Infection with Helicobacter pylori is the strongest risk factor for the development of chronic gastritis, gastric ulcer and gastric carcinoma. The majority of the H. pylori-infected population remains asymptomatic, and only 1% of individuals may progress to gastric cancer. The clinical outcomes caused by H. pylori infection are considered to be associated with bacterial virulence, genetic polymorphism of hosts as well as environmental factors. Most H. pylori strains possess a cytotoxin-associated gene (cag) pathogenicity island (cagPAI), encoding a 120-140 kDa CagA protein, which is the most important bacterial oncoprotein...
October 4, 2016: Oncology Reports
Anahita Javaheri, Tobias Kruse, Kristof Moonens, Raquel Mejías-Luque, Ayla Debraekeleer, Carmen I Asche, Nicole Tegtmeyer, Behnam Kalali, Nina C Bach, Stephan A Sieber, Darryl J Hill, Verena Königer, Christof R Hauck, Roman Moskalenko, Rainer Haas, Dirk H Busch, Esther Klaile, Hortense Slevogt, Alexej Schmidt, Steffen Backert, Han Remaut, Bernhard B Singer, Markus Gerhard
Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8...
October 17, 2016: Nature Microbiology
Petya Berger, Michael Knödler, Konrad U Förstner, Michael Berger, Christian Bertling, Cynthia M Sharma, Jörg Vogel, Helge Karch, Ulrich Dobrindt, Alexander Mellmann
Escherichia coli O104:H4 (E. coli O104:H4), which caused a massive outbreak of acute gastroenteritis and hemolytic uremic syndrome in 2011, carries an aggregative adherence fimbriae I (AAF/I) encoding virulence plasmid, pAA. The importance of pAA in host-pathogen interaction and disease severity has been demonstrated, however, not much is known about its transcriptional organization and gene regulation. Here, we analyzed the pAA primary transcriptome using differential RNA sequencing, which allows for the high-throughput mapping of transcription start site (TSS) and non-coding RNA candidates...
October 17, 2016: Scientific Reports
Liqin Wang, Miao Xu, Noel Southall, Wei Zheng, Shuishu Wang
Tuberculosis (TB) still kills over 1.5 million people per year despite available anti-TB drugs. The emergence of drug-resistant TB poses a major threat to public health and prompts for an urgent need for new and more effective drugs. The long duration needed to treat TB by the current TB drugs, which target the essential cellular activities, inevitably leads to the emergence of drug-resistance. PhoP of Mycobacterium tuberculosis (MTB), an essential virulence factor, is a novel target for drug development. Guided by the crystal structure of the PhoP-DNA complex, we designed and developed a robust high-throughput screening assay for identification of PhoP inhibitors that disrupt the PhoP-DNA binding...
October 10, 2016: Combinatorial Chemistry & High Throughput Screening
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