Pathogens

10 pages, 2628 KiB

Open AccessReview

by Jeniel E. Nett

University of Wisconsin-Madison, Departments of Medicine, Medical Microbiology and Immunology, 5203 Microbial Sciences Building, 1550 Linden Drive, Madison, WI 53706, USA

Pathogens 2016, 5(1), 33; https://doi.org/10.3390/pathogens5010033 - 18 Mar 2016

Cited by 44 | Viewed by 7508

Abstract

Candida spp. are among the most common nosocomial fungal pathogens and are notorious for their propensity toward biofilm formation. When growing on a medical device or mucosal surface, these organisms reside as communities embedded in a protective matrix, resisting host defenses. The host [...] Read more.

Candida spp. are among the most common nosocomial fungal pathogens and are notorious for their propensity toward biofilm formation. When growing on a medical device or mucosal surface, these organisms reside as communities embedded in a protective matrix, resisting host defenses. The host responds to Candida biofilm by depositing a variety of proteins that become incorporated into the biofilm matrix. Compared to free-floating Candida, leukocytes are less effective against Candida within a biofilm. This review highlights recent advances describing the host’s response to Candida biofilms using ex vivo and in vivo models of mucosal and device-associated biofilm infections. Full article

(This article belongs to the Special Issue Human Fungal Pathogens)

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13 pages, 1968 KiB

Open AccessReview

Evasion of Neutrophil Killing by Staphylococcus aureus

by Will A. McGuinness, Scott D. Kobayashi and Frank R. DeLeo^*

Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA

Pathogens 2016, 5(1), 32; https://doi.org/10.3390/pathogens5010032 - 17 Mar 2016

Cited by 59 | Viewed by 16591

Abstract

Staphylococcus aureus causes many types of infections, ranging from self-resolving skin infections to severe or fatal pneumonia. Human innate immune cells, called polymorphonuclear leukocytes (PMNs or neutrophils), are essential for defense against S. aureus infections. Neutrophils are the most prominent cell type of [...] Read more.

Staphylococcus aureus causes many types of infections, ranging from self-resolving skin infections to severe or fatal pneumonia. Human innate immune cells, called polymorphonuclear leukocytes (PMNs or neutrophils), are essential for defense against S. aureus infections. Neutrophils are the most prominent cell type of the innate immune system and are capable of producing non-specific antimicrobial molecules that are effective at eliminating bacteria. Although significant progress has been made over the past few decades, our knowledge of S. aureus-host innate immune system interactions is incomplete. Most notably, S. aureus has the capacity to produce numerous molecules that are directed to protect the bacterium from neutrophils. Here we review in brief the role played by neutrophils in defense against S. aureus infection, and correspondingly, highlight selected S. aureus molecules that target key neutrophil functions. Full article

(This article belongs to the Special Issue Staphylococcus Aureus Infection)

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23 pages, 647 KiB

Open AccessArticle

The T Cell Response to Staphylococcus aureus

by Barbara M. Bröker^*, Daniel Mrochen

and Vincent Péton

Department of Immunology, University Medicine Greifswald, Sauerbruchstraße DZ7, 17475 Greifswald, Germany

Pathogens 2016, 5(1), 31; https://doi.org/10.3390/pathogens5010031 - 17 Mar 2016

Cited by 101 | Viewed by 14128

Abstract

Staphylococcus aureus (S. aureus) is a dangerous pathogen and a leading cause of both nosocomial and community acquired bacterial infection worldwide. However, on the other hand, we are all exposed to this bacterium, often within the first hours of life, and [...] Read more.

Staphylococcus aureus (S. aureus) is a dangerous pathogen and a leading cause of both nosocomial and community acquired bacterial infection worldwide. However, on the other hand, we are all exposed to this bacterium, often within the first hours of life, and usually manage to establish equilibrium and coexist with it. What does the adaptive immune system contribute toward lifelong control of S. aureus? Will it become possible to raise or enhance protective immune memory by vaccination? While in the past the S. aureus-specific antibody response has dominated this discussion, the research community is now coming to appreciate the role that the cellular arm of adaptive immunity, the T cells, plays. There are numerous T cell subsets, each with differing functions, which together have the ability to orchestrate the immune response to S. aureus and hence to tip the balance between protection and pathology. This review summarizes the state of the art in this dynamic field of research. Full article

(This article belongs to the Special Issue Staphylococcus Aureus Infection)

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18 pages, 1939 KiB

Open AccessReview

Adhesive Pili in UTI Pathogenesis and Drug Development

by Caitlin N. Spaulding¹ and Scott J. Hultgren^1,2,*

¹ Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA

² Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA

Pathogens 2016, 5(1), 30; https://doi.org/10.3390/pathogens5010030 - 15 Mar 2016

Cited by 81 | Viewed by 13972

Abstract

Urinary tract infections (UTIs) are one of the most common bacterial infections, affecting 150 million people each year worldwide. High recurrence rates and increasing antimicrobial resistance among uropathogens are making it imperative to develop alternative strategies for the treatment and prevention of this [...] Read more.

Urinary tract infections (UTIs) are one of the most common bacterial infections, affecting 150 million people each year worldwide. High recurrence rates and increasing antimicrobial resistance among uropathogens are making it imperative to develop alternative strategies for the treatment and prevention of this common infection. In this Review, we discuss how understanding the: (i) molecular and biophysical basis of host-pathogen interactions; (ii) consequences of the molecular cross-talk at the host pathogen interface in terms of disease progression; and (iii) pathophysiology of UTIs is leading to efforts to translate this knowledge into novel therapeutics to treat and prevent these infections. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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16 pages, 1598 KiB

Open AccessArticle

Convective Mixing in Distal Pipes Exacerbates Legionella pneumophila Growth in Hot Water Plumbing

by William J. Rhoads^*, Amy Pruden and Marc A. Edwards

Via Department of Civil and Environmental Engineering, Virginia Tech, 1145 Perry St., 401 Durham Hall, Blacksburg, VA 24061, USA

Pathogens 2016, 5(1), 29; https://doi.org/10.3390/pathogens5010029 - 12 Mar 2016

Cited by 33 | Viewed by 7162

Abstract

Legionella pneumophila is known to proliferate in hot water plumbing systems, but little is known about the specific physicochemical factors that contribute to its regrowth. Here, L. pneumophila trends were examined in controlled, replicated pilot-scale hot water systems with continuous recirculation lines subject [...] Read more.

Legionella pneumophila is known to proliferate in hot water plumbing systems, but little is known about the specific physicochemical factors that contribute to its regrowth. Here, L. pneumophila trends were examined in controlled, replicated pilot-scale hot water systems with continuous recirculation lines subject to two water heater settings (40 °C and 58 °C) and three distal tap water use frequencies (high, medium, and low) with two pipe configurations (oriented upward to promote convective mixing with the recirculating line and downward to prevent it). Water heater temperature setting determined where L. pneumophila regrowth occurred in each system, with an increase of up to 4.4 log gene copies/mL in the 40 °C system tank and recirculating line relative to influent water compared to only 2.5 log gene copies/mL regrowth in the 58 °C system. Distal pipes without convective mixing cooled to room temperature (23–24 °C) during periods of no water use, but pipes with convective mixing equilibrated to 30.5 °C in the 40 °C system and 38.8 °C in the 58 °C system. Corresponding with known temperature effects on L. pneumophila growth and enhanced delivery of nutrients, distal pipes with convective mixing had on average 0.2 log more gene copies/mL in the 40 °C system and 0.8 log more gene copies/mL in the 58 °C system. Importantly, this work demonstrated the potential for thermal control strategies to be undermined by distal taps in general, and convective mixing in particular. Full article

(This article belongs to the Special Issue Pathogen Legionella pneumophila)

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8 pages, 433 KiB

Open AccessArticle

Ciprofloxacin-Induced Antibacterial Activity Is Atteneuated by Pretreatment with Antioxidant Agents

by Majed M. Masadeh^1,*, Karem H. Alzoubi²

, Sayer I. Al-azzam², Omar F. Khabour³

and Ahlam M. Al-buhairan⁴

¹ Department of Pharmaceutical Technology, Jordan University of Science and Technology, Irbid 22110, Jordan

² Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan

³ Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan

⁴ College of applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia

Pathogens 2016, 5(1), 28; https://doi.org/10.3390/pathogens5010028 - 9 Mar 2016

Cited by 27 | Viewed by 6437

Abstract

Ciprofloxacin works through interfering with replication and transcription of bacterial DNA, which leads to increased oxidative stress, and death of bacterial cells. Drugs with strong antioxidant such as tempol, melatonin and pentoxifylline might interfere with the antibacterial activity of ciprofloxacin. In the current [...] Read more.

Ciprofloxacin works through interfering with replication and transcription of bacterial DNA, which leads to increased oxidative stress, and death of bacterial cells. Drugs with strong antioxidant such as tempol, melatonin and pentoxifylline might interfere with the antibacterial activity of ciprofloxacin. In the current study, the effect of these drugs on the cytotoxicity of ciprofloxacin was investigated against several reference bacteria. Standard bacterial strains included Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923). The antibacterial activity of ciprofloxacin with or without treatment of bacterial cells by tempol, melatonin or pentoxifylline was assessed using the disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All of the tested bacterial strains were sensitive to ciprofloxacin. When treated with tempol, melatonin or pentoxifylline, all bacterial strains showed significantly smaller zones of inhibition and larger MIC values compared ciprofloxacin alone. In correlation, reactive oxygen species (ROS) generation induced by ciprofloxacin antibacterial action was diminished by treatment of bacterial cells with tempol, melatonin or pentoxifylline. In conclusion, results indicate the possible antagonistic properties for agents with antioxidant properties such as tempol, melatonin and pentoxifylline when they are used concurrently with flouroquinolones. This could be related to the ability of these agents to inhibit oxidative stress in bacterial cells. Full article

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12 pages, 2227 KiB

Open AccessConference Report

Cytoprotective Effect of Lactobacillus crispatus CTV-05 against Uropathogenic E. coli

by Daniel S. C. Butler¹

, Aurelio Silvestroni² and Ann E. Stapleton^2,*

¹ Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, 221 00 Lund, Sweden

² Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195-5852, USA

Pathogens 2016, 5(1), 27; https://doi.org/10.3390/pathogens5010027 - 8 Mar 2016

Cited by 19 | Viewed by 7391

Abstract

The vaginal flora consists of a subset of different lactic acid producing bacteria, typically creating a hostile environment for infecting pathogens. However, the flora can easily be disrupted, creating a favorable milieu for uropathogenic Escherichia coli (UPEC), making it possible to further infect [...] Read more.

The vaginal flora consists of a subset of different lactic acid producing bacteria, typically creating a hostile environment for infecting pathogens. However, the flora can easily be disrupted, creating a favorable milieu for uropathogenic Escherichia coli (UPEC), making it possible to further infect the urinary system via the urethra. Probiotic use of different lactobacilli to restore the normal flora of the vagina has been proposed as a potential prophylactic treatment against urinary tract infections. This project evaluated the protective- and anti-inflammatory roles of the probiotic Lactobacillus crispatus strain CTV-05 in an in vitro system. The inflammatory response and the cytotoxic effect were studied by Enzyme-linked immunosorbent assays and by trypan blue exclusion of cells inoculated with L. crispatus CTV-05 and comparing it to non-infected controls and UPEC infected cells. L. crispatus CTV-05 showed no cytotoxicity to vaginal epithelial cells compared to non-infected controls and provided significant protection against UPEC infection (p < 0.05). Further more, L. crispatus CTV-05 did not create a pro-inflammatory response in vitro, with no significant increase of IL-1β or IL-6. These results demonstrate the protective effect of using L. crispatus CTV-05 as a probiotic treatment to reduce the risk of recurrent urinary tract infections. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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1 pages, 145 KiB

Open AccessCorrection

Correction: Global Occurrence and Emission of Rotaviruses to Surface Waters. Pathogens 2015, 4, 229–255

by Nicholas M. Kiulia^1,2,*,†, Nynke Hofstra^3,†, Lucie C. Vermeulen³, Maureen A. Obara¹, Gertjan Medema^4,5 and Joan B. Rose¹

¹ Department of Fisheries and Wildlife, Michigan State University East Lansing, MI 48824, USA

² Enteric Viruses Research Group, Institute of Primate Research, P.O Box 24481, 00502 Karen, Nairobi, Kenya

³ Environmental Systems Analysis Group, Wageningen University, P.O. Box 47, 6700 AA, Wageningen, The Netherlands

⁴ Faculty of Civil Engineering and Geosciences, Delft University of Technology, P.O. Box 5048, 2600 GA, Delft, The Netherlands

⁵ KWR Watercycle Research Institute, Groningenhaven 7, 3433 PE, Nieuwegein, The Netherlands

^† These authors contributed equally to this work.

Pathogens 2016, 5(1), 26; https://doi.org/10.3390/pathogens5010026 - 1 Mar 2016

Cited by 1 | Viewed by 3731

Abstract

The authors wish to make the following corrections to their paper [1].[...] Full article

(This article belongs to the Special Issue Waterborne Pathogens)

8 pages, 707 KiB

Open AccessConference Report

A Comparative Analysis of the Mechanism of Toll-Like Receptor-Disruption by TIR-Containing Protein C from Uropathogenic Escherichia coli

by Anna Waldhuber¹, Greg A. Snyder², Franziska Römmler¹, Christine Cirl¹, Tina Müller¹, Tsan Sam Xiao³, Catharina Svanborg⁴ and Thomas Miethke^5,*

¹ Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Trogerstr. 30, München 81675, Germany

² Institute of Human Virology, Departments of Medicine, and Microbiology and Immunology, University of Maryland, School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA

³ Department of Pathology, Case Western Reserve University, 2103 Cornell Rd, Cleveland, OH 44106, USA

⁴ Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, 221 00 Lund, Sweden

⁵ Institute of Medical Microbiology and Hygiene, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany

Pathogens 2016, 5(1), 25; https://doi.org/10.3390/pathogens5010025 - 29 Feb 2016

Cited by 15 | Viewed by 5735

Abstract

The TIR-containing protein C (TcpC) of uropathogenic Escherichia coli strains is a powerful virulence factor by impairing the signaling cascade of Toll-like receptors (TLRs). Several other bacterial pathogens like Salmonella, Yersinia, Staphylococcus aureus but also non-pathogens express similar proteins. We discuss [...] Read more.

The TIR-containing protein C (TcpC) of uropathogenic Escherichia coli strains is a powerful virulence factor by impairing the signaling cascade of Toll-like receptors (TLRs). Several other bacterial pathogens like Salmonella, Yersinia, Staphylococcus aureus but also non-pathogens express similar proteins. We discuss here the pathogenic potential of TcpC and its interaction with TLRs and TLR-adapter proteins on the molecular level and compare its activity with the activity of other bacterial TIR-containing proteins. Finally, we analyze and compare the structure of bacterial TIR-domains with the TIR-domains of TLRs and TLR-adapters. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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9 pages, 5076 KiB

Open AccessReview

Urinary Tract Infection Molecular Mechanisms and Clinical Translation

by Gabriela Godaly^*

, Ines Ambite

, Manoj Puthia, Aftab Nadeem, James Ho, Karoly Nagy, Yujing Huang, Gustav Rydström and Catharina Svanborg

Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, 221 00 Lund, Sweden

Pathogens 2016, 5(1), 24; https://doi.org/10.3390/pathogens5010024 - 24 Feb 2016

Cited by 20 | Viewed by 7514

Abstract

Rapid developments in infection biology create new and exciting options for individualized diagnostics and therapy. Such new practices are needed to improve patient survival and reduce morbidity. Molecular determinants of host resistance to infection are being characterized, making it possible to identify susceptible [...] Read more.

Rapid developments in infection biology create new and exciting options for individualized diagnostics and therapy. Such new practices are needed to improve patient survival and reduce morbidity. Molecular determinants of host resistance to infection are being characterized, making it possible to identify susceptible individuals and to predict their risk for future morbidity. Immunotherapy is emerging as a new strategy to treat infections worldwide and controlled boosting of the host immune defense represents an important therapeutic alternative to antibiotics. In proof of concept studies, we have demonstrated that this approach is feasible. The long-term goal is not just to remove the pathogens but to also develop technologies that restore resistance to infection in disease-prone patients and devise personalized therapeutic interventions. Here, we discuss some approaches to reaching these goals, in patients with urinary tract infection (UTI). We describe critical host signaling pathways that define symptoms and pathology and the genetic control of innate immune responses that balance protection against tissue damage. For some of these genes, human relevance has been documented in clinical studies, identifying them as potential targets for immune-modulatory therapies, as a complement to antibiotics. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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8 pages, 1366 KiB

Open AccessReview

Perspective: Adhesion Mediated Signal Transduction in Bacterial Pathogens

by Sudha Moorthy¹, Julia Keklak¹ and Eric A. Klein^1,2,*

¹ Biology Department, Rutgers University-Camden, 200 Federal St., Suite 520, Camden, NJ 08103, USA

² Center for Computational and Integrative Biology, Rutgers University-Camden, 200 Federal St., Suite 520, Camden, NJ 08103, USA

Pathogens 2016, 5(1), 23; https://doi.org/10.3390/pathogens5010023 - 18 Feb 2016

Cited by 13 | Viewed by 8278

Abstract

During the infection process, pathogenic bacteria undergo large-scale transcriptional changes to promote virulence and increase intrahost survival. While much of this reprogramming occurs in response to changes in chemical environment, such as nutrient availability and pH, there is increasing evidence that adhesion to [...] Read more.

During the infection process, pathogenic bacteria undergo large-scale transcriptional changes to promote virulence and increase intrahost survival. While much of this reprogramming occurs in response to changes in chemical environment, such as nutrient availability and pH, there is increasing evidence that adhesion to host-tissue can also trigger signal transduction pathways resulting in differential gene expression. Determining the molecular mechanisms of adhesion-mediated signaling requires disentangling the contributions of chemical and mechanical stimuli. Here we highlight recent work demonstrating that surface attachment drives a transcriptional response in bacterial pathogens, including uropathogenic Escherichia coli (E. coli), and discuss the complexity of experimental design when dissecting the specific role of adhesion-mediated signaling during infection. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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17 pages, 710 KiB

Open AccessReview

The Role of Staphylococcus aureus Virulence Factors in Skin Infection and Their Potential as Vaccine Antigens

by Keenan A. Lacey^1,2

, Joan A. Geoghegan² and Rachel M. McLoughlin^1,*

¹ Host Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland

² Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland

Pathogens 2016, 5(1), 22; https://doi.org/10.3390/pathogens5010022 - 17 Feb 2016

Cited by 110 | Viewed by 25602

Abstract

Staphylococcus aureus (S. aureus) causes the vast majority of skin and soft tissue infections (SSTIs) in humans. S. aureus has become increasingly resistant to antibiotics and there is an urgent need for new strategies to tackle S. aureus infections. Vaccines offer [...] Read more.

Staphylococcus aureus (S. aureus) causes the vast majority of skin and soft tissue infections (SSTIs) in humans. S. aureus has become increasingly resistant to antibiotics and there is an urgent need for new strategies to tackle S. aureus infections. Vaccines offer a potential solution to this epidemic of antimicrobial resistance. However, the development of next generation efficacious anti-S. aureus vaccines necessitates a greater understanding of the protective immune response against S. aureus infection. In particular, it will be important to ascertain if distinct immune mechanisms are required to confer protection at distinct anatomical sites. Recent discoveries have highlighted that interleukin-17-producing T cells play a particularly important role in the immune response to S. aureus skin infection and suggest that vaccine strategies to specifically target these types of T cells may be beneficial in the treatment of S. aureus SSTIs. S. aureus expresses a large number of cell wall-anchored (CWA) proteins, which are covalently attached to the cell wall peptidoglycan. The virulence potential of many CWA proteins has been demonstrated in infection models; however, there is a paucity of information regarding their roles during SSTIs. In this review, we highlight potential candidate antigens for vaccines targeted at protection against SSTIs. Full article

(This article belongs to the Special Issue Staphylococcus Aureus Infection)

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8 pages, 1124 KiB

Open AccessReview

Asymtomatic Bacteriuria as a Model to Study the Coevolution of Hosts and Bacteria

by Ulrich Dobrindt^1,*

, Björn Wullt² and Catharina Svanborg²

¹ Institute of Hygiene, University of Münster, Mendelstr. 7, D-48149 Münster, Germany

² Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, S-223 62 Lund, Sweden

Pathogens 2016, 5(1), 21; https://doi.org/10.3390/pathogens5010021 - 15 Feb 2016

Cited by 25 | Viewed by 7376

Abstract

During asymptomatic bacteriuria (ABU), bacteria colonize the urinary tract for extended periods of time without causing symptoms of urinary tract infection. Previous studies indicate that many Escherichia coli (E. coli) strains that cause ABU have evolved from uropathogenic E. coli (UPEC) [...] Read more.

During asymptomatic bacteriuria (ABU), bacteria colonize the urinary tract for extended periods of time without causing symptoms of urinary tract infection. Previous studies indicate that many Escherichia coli (E. coli) strains that cause ABU have evolved from uropathogenic E. coli (UPEC) by reductive evolution and loss of the ability to express functional virulence factors. For instance, the prototype ABU strain 83972 has a smaller genome than UPEC strains with deletions or point mutations in several virulence genes. To understand the mechanisms of bacterial adaptation and to find out whether the bacteria adapt in a host-specific manner, we compared the complete genome sequences of consecutive reisolates of ABU strain 83972 from different inoculated individuals and compared them with the genome of the parent strain. Reisolates from different hosts exhibited individual patterns of genomic alterations. Non-synonymous SNPs predominantly occurred in coding regions and often affected the amino acid sequence of proteins with global or pleiotropic regulatory function. These gene products are involved in different bacterial stress protection strategies, and metabolic and signaling pathways. Our data indicate that adaptation of E. coli 83972 to prolonged growth in the urinary tract involves responses to specific growth conditions and stresses present in the individual hosts. Accordingly, modulation of gene expression required for survival and growth under stress conditions seems to be most critical for long-term growth of E. coli 83972 in the urinary tract. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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11 pages, 4009 KiB

Open AccessArticle

Histone Deacetylase 6 Regulates Bladder Architecture and Host Susceptibility to Uropathogenic Escherichia coli

by Adam J. Lewis¹, Bijaya K. Dhakal¹, Ting Liu² and Matthew A. Mulvey^1,*

¹ Department of Pathology, University of Utah, 15 N. Medical Drive E., Salt Lake City, UT 84112, USA

² Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA

Pathogens 2016, 5(1), 20; https://doi.org/10.3390/pathogens5010020 - 14 Feb 2016

Cited by 5 | Viewed by 5835

Abstract

Histone deacetylase 6 (HDAC6) is a non-canonical, mostly cytosolic histone deacetylase that has a variety of interacting partners and substrates. Previous work using cell-culture based assays coupled with pharmacological inhibitors and gene-silencing approaches indicated that HDAC6 promotes the actin- and microtubule-dependent invasion of [...] Read more.

Histone deacetylase 6 (HDAC6) is a non-canonical, mostly cytosolic histone deacetylase that has a variety of interacting partners and substrates. Previous work using cell-culture based assays coupled with pharmacological inhibitors and gene-silencing approaches indicated that HDAC6 promotes the actin- and microtubule-dependent invasion of host cells by uropathogenic Escherichia coli (UPEC). These facultative intracellular pathogens are the major cause of urinary tract infections. Here, we examined the involvement of HDAC6 in bladder colonization by UPEC using HDAC6 knockout mice. Though UPEC was unable to invade HDAC6^−/− cells in culture, the bacteria had an enhanced ability to colonize the bladders of mice that lacked HDAC6. This effect was transient, and by six hours post-inoculation bacterial titers in the HDAC6^−/− mice were reduced to levels seen in wild type control animals. Subsequent analyses revealed that the mutant mice had greater bladder volume capacity and fluid retention, along with much higher levels of acetylated a-tubulin. In addition, infiltrating neutrophils recovered from the HDAC6^−/− bladder harbored significantly more viable bacteria than their wild type counterparts. Cumulatively, these changes may negate any inhibitory effects that the lack of HDAC6 has on UPEC entry into individual host cells, and suggest roles for HDAC6 in other urological disorders such as urinary retention. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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8 pages, 1225 KiB

Open AccessReview

Why Serological Responses during Cystitis are Limited

by Hae Woong Choi^1,* and Soman N. Abraham^1,2,3,4,*

¹ Departments of Pathology, Duke University Medical Center, Durham, NC 27710, USA

² Immunology Duke University Medical Center, Durham, NC 27710, USA

³ Molecular Genetics & Microbiology Duke University Medical Center, Durham, NC 27710, USA

⁴ Program in Emerging Infectious Diseases Duke-National University of Singapore, Singapore 169857, Singapore

Pathogens 2016, 5(1), 19; https://doi.org/10.3390/pathogens5010019 - 14 Feb 2016

Cited by 6 | Viewed by 4721

Abstract

The high frequency of urinary tract infections (UTIs), some of which appear to be endogenous relapses rather than reinfections by new isolates, point to defects in the host’s memory immune response. It has been known for many decades that, whereas kidney infections evoked [...] Read more.

The high frequency of urinary tract infections (UTIs), some of which appear to be endogenous relapses rather than reinfections by new isolates, point to defects in the host’s memory immune response. It has been known for many decades that, whereas kidney infections evoked an antibody response to the infecting bacteria, infections limited to the bladder failed to do so. We have identified the existence of a broadly immunosuppressive transcriptional program associated with the bladder, but not the kidneys, during infection of the urinary tract that is dependent on bladder mast cells. This involves the localized secretion of IL-10 and results in the suppression of humoral immune responses in the bladder. Mast cell-mediated immune suppression could suggest a role for these cells in critically balancing the needs to clear infections with the imperative to prevent harmful immune reactions in the host. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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43 pages, 1319 KiB

Open AccessReview

The Role of Gammaherpesviruses in Cancer Pathogenesis

by Hem Chandra Jha^†

, Shuvomoy Banerjee^† and Erle S. Robertson^*

¹ Department of Microbiology and Tumor Virology Program, Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610, Hamilton Walk, Philadelphia, PA 19104, USA

^† These authors contributed equally.

Pathogens 2016, 5(1), 18; https://doi.org/10.3390/pathogens5010018 - 6 Feb 2016

Cited by 109 | Viewed by 12105

Abstract

Worldwide, one fifth of cancers in the population are associated with viral infections. Among them, gammaherpesvirus, specifically HHV4 (EBV) and HHV8 (KSHV), are two oncogenic viral agents associated with a large number of human malignancies. In this review, we summarize the current understanding [...] Read more.

Worldwide, one fifth of cancers in the population are associated with viral infections. Among them, gammaherpesvirus, specifically HHV4 (EBV) and HHV8 (KSHV), are two oncogenic viral agents associated with a large number of human malignancies. In this review, we summarize the current understanding of the molecular mechanisms related to EBV and KSHV infection and their ability to induce cellular transformation. We describe their strategies for manipulating major cellular systems through the utilization of cell cycle, apoptosis, immune modulation, epigenetic modification, and altered signal transduction pathways, including NF-kB, Notch, Wnt, MAPK, TLR, etc. We also discuss the important EBV latent antigens, namely EBNA1, EBNA2, EBNA3’s and LMP’s, which are important for targeting these major cellular pathways. KSHV infection progresses through the engagement of the activities of the major latent proteins LANA, v-FLIP and v-Cyclin, and the lytic replication and transcription activator (RTA). This review is a current, comprehensive approach that describes an in-depth understanding of gammaherpes viral encoded gene manipulation of the host system through targeting important biological processes in viral-associated cancers. Full article

(This article belongs to the Special Issue Viral Pathogenesis)

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13 pages, 3138 KiB

Open AccessArticle

First Description of Infection of Caprine Herpesvirus 1 (CpHV-1) in Goats in Mainland France

by Florence Suavet¹, Jean-Luc Champion², Luc Bartolini³, Maryline Bernou⁴, Jean-Pierre Alzieu⁵, Roland Brugidou⁶, Séverine Darnatigues⁷, Gaël Reynaud⁸, Cécile Perrin⁹, Gilbert Adam¹, Richard Thiéry^1,* and Véronique Duquesne¹

¹ Anses, Sophia-Antipolis Laboratory, 105 Route des Chappes, BP111, 06902 Sophia-Antipolis, France

² Coopérative de l’Agneau de Haute-Provence, 04000 Digne Les Bains, France

³ Alpes-Maritimes Veterinary Laboratory, 06902 Sophia-Antipolis, France

⁴ Pyrénées-Tarbes Laboratory, Centre des Affaires Kennedy, 65000 Tarbes, France

⁵ Ariège Veterinary Laboratory, Rue las Escoumes, 09008 Foix, France

⁶ Aveyron Labo, 12031 Rodez, France

⁷ Tarn Analytical Laboratory, 81011 Albi, France

⁸ Savoie Analytical Laboratory, 73024 Chambéry, France

⁹ Anses, Niort Laboratory, 79012 Niort, France

Pathogens 2016, 5(1), 17; https://doi.org/10.3390/pathogens5010017 - 6 Feb 2016

Cited by 21 | Viewed by 5852

Abstract

The purpose of this study was to investigate the epidemiological situation of the caprine herpesvirus 1 (CpHV-1) infection in nine districts in mainland France, mostly in the south, near Italy or Spain, where high seroprevalence has been observed. Two more central areas were [...] Read more.

The purpose of this study was to investigate the epidemiological situation of the caprine herpesvirus 1 (CpHV-1) infection in nine districts in mainland France, mostly in the south, near Italy or Spain, where high seroprevalence has been observed. Two more central areas were also included in the study. The serosurvey was carried out in 9564 goats (275 herds) using bovine herpesvirus 1 (BoHV-1) glycoprotein B and E ELISAs. To confirm the presence of specific CpHV-1 antibodies, some of the samples were tested in neutralization assay. Results demonstrate, for the first time, CpHV-1 infection in goat herds on the French mainland. The analysis found cases of alphaherpesviruses infection in each district studied, with different levels of seroprevalence observed within each district (ranging from 0.2% to 31.56% at an individual level and from 9% to 46.2% for herd seroprevalence). Moreover, in the Alpes-Maritimes district, the seroprevalence seemed to be higher in older goats (79.45% of animals 6 years old or more) than in younger animals (40.99% of one-year-olds). This result suggests frequent virus re-excretion and circulation in herds. Results analysis also shows that the seroprevalence was higher when the herd size increased. In addition, the first French CpHV-1 strain was isolated from nasal swabs taken on an infected goat. The data reported herein demonstrate that CpHV-1 circulates in mainland France, which should henceforth be taken into consideration in cases of unexplained abortion in goats. Full article

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5 pages, 512 KiB

Open AccessArticle

Biomimickry of UPEC Cytoinvasion: A Novel Concept for Improved Drug Delivery in UTI

by Clara Maria Pichl^*,†, Bernhard Dunkl^†, Bernhard Brauner^†, Franz Gabor^†, Michael Wirth^† and Lukas Neutsch^†

¹ Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria

^† These authors contributed equally to this work.

Pathogens 2016, 5(1), 16; https://doi.org/10.3390/pathogens5010016 - 4 Feb 2016

Cited by 12 | Viewed by 6181

Abstract

Urinary tract infections (UTIs) are among the most common bacterial infections. In an increasing number of cases, pathogen (multi-)resistance hampers durable treatment success via the standard therapies. On the functional level, the activity of urinary excreted antibiotics is compromized by the efficient tissue [...] Read more.

Urinary tract infections (UTIs) are among the most common bacterial infections. In an increasing number of cases, pathogen (multi-)resistance hampers durable treatment success via the standard therapies. On the functional level, the activity of urinary excreted antibiotics is compromized by the efficient tissue colonization mechanism of uropathogenic Escherichia coli (UPEC). Advanced drug delivery systems aim at exploiting a glycan-mediated targeting mechanism, similar to the UPEC invasion pathway, to increase bioavailability. This may be realized by conjugation of intravesically applied drugs or drug carriers to chosen plant lectins. Higher local drug concentrations in or nearby bacterial reservoirs may be gained, with higher chances for complete eradication. In this study, preliminary parameters to clarify the potential of this biorecognitive approach were evaluated. Glycan-triggered interaction cascades and uptake processes of several plant lectins with distinct carbohydrate specificities were characterized, and wheat germ agglutinin (WGA) could be identified as the most promising targeter for crossing the urothelial membrane barrier. In partially differentiated primary cells, intracellular accumulation sites were largely identical for GlcNAc- and Mannose-specific lectins. This indicates that WGA-mediated delivery may also enter host cells via the FimH-dependent uptake pathway. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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7 pages, 514 KiB

Open AccessArticle

Neutrophil Migration into the Infected Uroepithelium Is Regulated by the Crosstalk between Resident and Helper Macrophages

by Kristina Zec¹, Julia Volke¹, Nirojah Vijitha¹, Stephanie Thiebes¹, Matthias Gunzer¹, Christian Kurts² and Daniel Robert Engel^1,*

¹ Institute of Experimental Immunology and Imaging, Department Immunodynamics, University Hospital Essen, University Duisburg-Essen, Essen 45141, Germany

² Institute of Experimental Immunology, University Hospital Bonn, Bonn 53127, Germany

Pathogens 2016, 5(1), 15; https://doi.org/10.3390/pathogens5010015 - 4 Feb 2016

Cited by 20 | Viewed by 6399

Abstract

The antibacterial defense against infections depends on the cooperation between distinct phagocytes of the innate immune system, namely macrophages and neutrophils. However, the mechanisms driving this cooperation are incompletely understood. In this study we describe the crosstalk between Ly6C⁺ and Ly6C⁻ [...] Read more.

The antibacterial defense against infections depends on the cooperation between distinct phagocytes of the innate immune system, namely macrophages and neutrophils. However, the mechanisms driving this cooperation are incompletely understood. In this study we describe the crosstalk between Ly6C⁺ and Ly6C⁻ macrophage-subtypes and neutrophils in the context of urinary tract infection (UTI) with uropathogenic E. coli (UPEC). Ly6C⁻ macrophages acted as tissue resident sentinels and attracted circulating phagocytes by chemokines. Ly6C⁺ macrophages produced tumor necrosis factor (TNF) that licensed Ly6C⁻ macrophages to release preformed CXCL2, which in turn caused matrix metalloproteinases (MMP-9) secretion by neutrophils to enable transepithelial migration. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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5 pages, 498 KiB

Open AccessReview

Genetic Variations in Vesicoureteral Reflux Sequelae

by David S. Hains^1,* and Andrew L. Schwaderer²

¹ Innate Immunity Translational Research Center, Children’s Foundation Research Institute, Le Bonheur Children’s Hospital, Memphis, TN 38103, USA

² Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH 43205, USA

Pathogens 2016, 5(1), 14; https://doi.org/10.3390/pathogens5010014 - 2 Feb 2016

Cited by 4 | Viewed by 4914

Abstract

Urinary tract infections (UTI) are a common condition in children. Vesicoureteral reflux (VUR) represents a common associated condition with childhood UTI. UTI susceptibility appears to have a genetic component based on family and UTI cohort studies. Targeted analysis of innate immune system genetic [...] Read more.

Urinary tract infections (UTI) are a common condition in children. Vesicoureteral reflux (VUR) represents a common associated condition with childhood UTI. UTI susceptibility appears to have a genetic component based on family and UTI cohort studies. Targeted analysis of innate immune system genetic variations indicate that these variations are important in UTI susceptibility. In this overview, we discuss how current cohorts and genetic strategies can be implemented to discover new susceptibility loci in patients with UTI. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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14 pages, 226 KiB

Open AccessReview

Novel Strategies in the Prevention and Treatment of Urinary Tract Infections

by Petra Lüthje^† and Annelie Brauner^*

¹ Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm SE-171 76, Sweden

^† Current affiliation: Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm SE-141 86, Sweden

Pathogens 2016, 5(1), 13; https://doi.org/10.3390/pathogens5010013 - 27 Jan 2016

Cited by 34 | Viewed by 9721

Abstract

Urinary tract infections are one of the most common bacterial infections, especially in women and children, frequently treated with antibiotics. The alarming increase in antibiotic resistance is a global threat to future treatment of infections. Therefore, alternative strategies are urgently needed. The innate [...] Read more.

Urinary tract infections are one of the most common bacterial infections, especially in women and children, frequently treated with antibiotics. The alarming increase in antibiotic resistance is a global threat to future treatment of infections. Therefore, alternative strategies are urgently needed. The innate immune system plays a fundamental role in protecting the urinary tract from infections. Antimicrobial peptides form an important part of the innate immunity. They are produced by epithelial cells and neutrophils and defend the urinary tract against invading bacteria. Since efficient resistance mechanisms have not evolved among bacterial pathogens, much effort has been put into exploring the role of antimicrobial peptides and possibilities to utilize them in clinical practice. Here, we describe the impact of antimicrobial peptides in the urinary tract and ways to enhance the production by hormones like vitamin D and estrogen. We also discuss the potential of medicinal herbs to be used in the prophylaxis and the treatment of urinary tract infections. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

13 pages, 1241 KiB

Open AccessArticle

Importance of B Lymphocytes and the IgG-Binding Protein Sbi in Staphylococcus aureus Skin Infection

by Fan Zhao¹, Anita S. Chong² and Christopher P. Montgomery^1,*

¹ Department of Pediatrics, The University of Chicago, Knapp Center for Biomedical Discovery 5124, 900 E. 57th Street, Chicago, IL 60637, USA

² Department of Surgery, The University of Chicago, Chicago, IL 60637; USA

Pathogens 2016, 5(1), 12; https://doi.org/10.3390/pathogens5010012 - 27 Jan 2016

Cited by 8 | Viewed by 5834

Abstract

Recurrent Staphylococcus aureus infections are common, suggesting that immunity elicited by these infections is not protective. We previously reported that S. aureus skin infection (SSTI) elicited antibody-mediated immunity against secondary SSTI in BALB/c mice. In this study, we investigated the role of humoral [...] Read more.

Recurrent Staphylococcus aureus infections are common, suggesting that immunity elicited by these infections is not protective. We previously reported that S. aureus skin infection (SSTI) elicited antibody-mediated immunity against secondary SSTI in BALB/c mice. In this study, we investigated the role of humoral immunity and the IgG-binding proteins Sbi and SpA in S. aureus SSTI. We found that B lymphocyte-deficient μMT mice were highly susceptible to infection, compared with congenic BALB/c mice. Importantly, transfer of immune serum protected μMT mice, demonstrating an appropriate response to protective antibody. We found that deletion of sbi, but not spa, impaired virulence, as assessed by skin lesion severity, and that Sbi-mediated virulence required B lymphocytes/antibody. Furthermore, neither Sbi nor SpA impaired the elicited antibody response or protection against secondary SSTI. Taken together, these findings highlight a B lymphocyte/antibody-dependent role of Sbi in the pathogenesis of S. aureus SSTI, and demonstrate that neither Sbi nor SpA interfered with elicited antibody-mediated immunity. Full article

(This article belongs to the Special Issue Staphylococcus Aureus Infection)

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2 pages, 167 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Pathogens in 2015

by Pathogens Editorial Office

MDPI AG, Klybeckstrasse 64, CH-4057 Basel, Switzerland

Pathogens 2016, 5(1), 11; https://doi.org/10.3390/pathogens5010011 - 22 Jan 2016

Viewed by 3461

Abstract

The editors of Pathogens would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...] Full article

8 pages, 1727 KiB

Open AccessArticle

The Global Prevalence of Infections in Urology Study: A Long-Term, Worldwide Surveillance Study on Urological Infections

by Florian Wagenlehner^1,*,†, Zafer Tandogdu^2,†, Riccardo Bartoletti³, Tommaso Cai⁴

, Mete Cek⁵, Ekaterina Kulchavenya⁶

, Béla Köves⁷, Kurt Naber⁸, Tamara Perepanova⁹, Peter Tenke⁷, Björn Wullt¹⁰, Florian Bogenhard¹¹ and Truls Erik Bjerklund Johansen¹²

¹ Department of Urology, Paediatric Urology and Andrology, Justus-Liebig-University, D-35392 Giessen, Germany

² Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK

³ Department of Experimental and Clinical medicine, University of Florence, 4-50121 Florence, Italy

⁴ Department of Urology, Santa Chiara Regional Hospital, 38122 Trento, Italy

⁵ Department of Urology, Trakya Medical School, Edirne 22100, Turkey

⁶ TB Research Institute, Novosibirsk 630040, Russia

⁷ Jahn Ferenc South Pest Teaching Hospital, 1204 Budapest, Hungary

⁸ Department of Urology, Technical University of Munich, 80333 Munich, Germany

⁹ S.R. Urology Institute, Moscow 105425, Russia

¹⁰ Department of Microbiology, Immunology and Glycobiology, Lund University, 22100 Lund, Sweden

¹¹ Department of Bioinformatics, Technische Hochschule Mittelhessen, 35390 Giessen, Germany

¹² Department of Urology, Oslo University, 0586 Oslo, Norway

^† These authors contributed equally to this work.

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Pathogens 2016, 5(1), 10; https://doi.org/10.3390/pathogens5010010 - 19 Jan 2016

Cited by 75 | Viewed by 10949

Abstract

The Global Prevalence of Infections in Urology (GPIU) study is a worldwide-performed point prevalence study intended to create surveillance data on antibiotic resistance, type of urogenital infections, risk factors and data on antibiotic consumption, specifically in patients at urological departments with healthcare-associated urogenital [...] Read more.

The Global Prevalence of Infections in Urology (GPIU) study is a worldwide-performed point prevalence study intended to create surveillance data on antibiotic resistance, type of urogenital infections, risk factors and data on antibiotic consumption, specifically in patients at urological departments with healthcare-associated urogenital infections (HAUTI). Investigators registered data through a web-based application (http://gpiu.esiu.org/). Data collection includes the practice and characteristics of the hospital and urology ward. On a certain day in November, each year, all urological patients present in the urological department at 8:00 a.m. are screened for HAUTI encompassing their full hospital course from admission to discharge. Apart from the GPIU main study, several side studies are taking place, dealing with transurethral resection of the prostate, prostate biopsy, as well as urosepsis. The GPIU study has been annually performed since 2003. Eight-hundred fifty-six urology units from 70 countries have participated so far, including 27,542 patients. A proxy for antibiotic consumption is reflected by the application rates used for antibiotic prophylaxis for urological interventions. Resistance rates of most uropathogens against antibiotics were high, especially with a note of multidrug resistance. The severity of HAUTI is also increasing, 25% being urosepsis in recent years. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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6 pages, 681 KiB

Open AccessCommunication

Application and Optimization of relE as a Negative Selection Marker for Making Definitive Genetic Constructs in Uropathogenic Escherichia coli

by Varnica Khetrapal^1,†, Kurosh S. Mehershahi^1,†, Siyi Chen¹ and Swaine L. Chen^1,2,*

¹ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 10, Singapore 119074, Singapore

² Genome Institute of Singapore, Infectious Diseases Group, 60 Biopolis street, Genome, #02-01, Singapore 138672, Singapore

^† These authors contributed equally to this work.

Pathogens 2016, 5(1), 9; https://doi.org/10.3390/pathogens5010009 - 18 Jan 2016

Cited by 2 | Viewed by 4882

Abstract

Studies of Uropathogenic Escherichia coli (UPEC) pathogenesis have relied heavily on genetic manipulation to understand virulence factors. We applied a recently reported positive-negative selection system to create a series of unmarked, scarless FimH mutants that show identical phenotypes to previously reported marked FimH [...] Read more.

Studies of Uropathogenic Escherichia coli (UPEC) pathogenesis have relied heavily on genetic manipulation to understand virulence factors. We applied a recently reported positive-negative selection system to create a series of unmarked, scarless FimH mutants that show identical phenotypes to previously reported marked FimH mutants; these are now improved versions useful for definitive assignment of phenotypes to FimH mutations. We also increased the efficiency of this system by designing new primer sites, which should further improve the efficiency and convenience of using negative selection in UTI89, other UPEC, and other Enterobacteriaceae. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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22 pages, 730 KiB

Open AccessReview

Viral Interactions with PDZ Domain-Containing Proteins—An Oncogenic Trait?

by Claire D. James^1,2 and Sally Roberts^1,*

¹ Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK

² Present address; Virginia Commonwealth University, School of Dentistry, W. Baxter Perkinson Jr. Building, 521 North 11th Street, P.O. Box 980566, Richmond, VA 23298-0566, USA

Pathogens 2016, 5(1), 8; https://doi.org/10.3390/pathogens5010008 - 18 Jan 2016

Cited by 61 | Viewed by 11056

Abstract

Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in [...] Read more.

Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ) interaction modules. In many cases (but not always), the viruses have evolved to bind the PDZ domains using the same short linear peptide motifs found in host protein-PDZ interactions, and in some cases regulate the interactions in a similar fashion by phosphorylation. What is striking is that the diverse viruses target a common subset of PDZ proteins that are intimately involved in controlling cell polarity and the structure and function of intercellular junctions, including tight junctions. Cell polarity is fundamental to the control of cell proliferation and cell survival and disruption of polarity and the signal transduction pathways involved is a key event in tumourigenesis. This review focuses on the oncogenic viruses and the role of targeting PDZ proteins in the virus life cycle and the contribution of virus-PDZ protein interactions to virus-mediated oncogenesis. We highlight how many of the viral associations with PDZ proteins lead to deregulation of PI3K/AKT signalling, benefitting virus replication but as a consequence also contributing to oncogenesis. Full article

(This article belongs to the Special Issue Infection and Cancer)

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9 pages, 3716 KiB

Open AccessConference Report

Measuring Escherichia coli Gene Expression during Human Urinary Tract Infections

by Harry L. T. Mobley

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

Pathogens 2016, 5(1), 7; https://doi.org/10.3390/pathogens5010007 - 15 Jan 2016

Cited by 40 | Viewed by 12038

Abstract

Extraintestinal Escherichia coli (E. coli) evolved by acquisition of pathogenicity islands, phage, plasmids, and DNA segments by horizontal gene transfer. Strains are heterogeneous but virulent uropathogenic isolates more often have specific fimbriae, toxins, and iron receptors than commensal strains. One may [...] Read more.

Extraintestinal Escherichia coli (E. coli) evolved by acquisition of pathogenicity islands, phage, plasmids, and DNA segments by horizontal gene transfer. Strains are heterogeneous but virulent uropathogenic isolates more often have specific fimbriae, toxins, and iron receptors than commensal strains. One may ask whether it is the virulence factors alone that are required to establish infection. While these virulence factors clearly contribute strongly to pathogenesis, bacteria must survive by metabolizing nutrients available to them. By constructing mutants in all major metabolic pathways and co-challenging mice transurethrally with each mutant and the wild type strain, we identified which major metabolic pathways are required to infect the urinary tract. We must also ask what else is E. coli doing in vivo? To answer this question, we examined the transcriptome of E. coli CFT073 in the murine model of urinary tract infection (UTI) as well as for E. coli strains collected and analyzed directly from the urine of patients attending either a urology clinic or a university health clinic for symptoms of UTI. Using microarrays and RNA-seq, we measured in vivo gene expression for these uropathogenic E. coli strains, identifying genes upregulated during murine and human UTI. Our findings allow us to propose a new definition of bacterial virulence. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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16 pages, 704 KiB

Open AccessReview

How Chemotherapy Increases the Risk of Systemic Candidiasis in Cancer Patients: Current Paradigm and Future Directions

by Flora Teoh^1,2

and Norman Pavelka^1,2,*

¹ Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore

² School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore

Pathogens 2016, 5(1), 6; https://doi.org/10.3390/pathogens5010006 - 15 Jan 2016

Cited by 78 | Viewed by 12527

Abstract

Candida albicans is a fungal commensal and a major colonizer of the human skin, as well as of the gastrointestinal and genitourinary tracts. It is also one of the leading causes of opportunistic microbial infections in cancer patients, often presenting in a life-threatening, [...] Read more.

Candida albicans is a fungal commensal and a major colonizer of the human skin, as well as of the gastrointestinal and genitourinary tracts. It is also one of the leading causes of opportunistic microbial infections in cancer patients, often presenting in a life-threatening, systemic form. Increased susceptibility to such infections in cancer patients is attributed primarily to chemotherapy-induced depression of innate immune cells and weakened epithelial barriers, which are the body’s first-line defenses against fungal infections. Moreover, classical chemotherapeutic agents also have a detrimental effect on components of the adaptive immune system, which further play important roles in the antifungal response. In this review, we discuss the current paradigm regarding the mechanisms behind the increased risk of systemic candidiasis in cancer patients. We also highlight some recent findings, which suggest that chemotherapy may have more extensive effects beyond the human host, in particular towards C. albicans itself and the bacterial microbiota. The extent to which these additional effects contribute towards the development of candidiasis in chemotherapy-treated patients remains to be investigated. Full article

(This article belongs to the Special Issue Candida Albicans Infections)

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3 pages, 130 KiB

Open AccessEditorial

Pathogens, Commensals, and Immunity: From the Perspective of the Urinary Bladder

by Bruce Beutler

Center for the Genetics of Host Defense, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

Pathogens 2016, 5(1), 5; https://doi.org/10.3390/pathogens5010005 - 7 Jan 2016

Cited by 4 | Viewed by 4354

Abstract

Why study immunity as it pertains to the urinary bladder? [...] Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

6 pages, 168 KiB

Open AccessConference Report

Asymptomatic Bacteriuria in Clinical Urological Practice: Preoperative Control of Bacteriuria and Management of Recurrent UTI

by Tommaso Cai^1,*

, Sandra Mazzoli², Paolo Lanzafame³, Patrizio Caciagli⁴, Gianni Malossini¹, Gabriella Nesi⁵, Florian M. E. Wagenlehner⁶, Bela Köves⁷, Robert Pickard⁸, Magnus Grabe⁹, Truls E. Bjerklund Johansen¹⁰ and Riccardo Bartoletti¹¹

¹ Department of Urology, Santa Chiara Regional Hospital, Largo Medaglie d’Oro 9, 38123 Trento, Italy

² Sexually Transmitted Disease Centre, Santa Maria Annunziata Hospital, 50012 Florence, Italy

³ Department of Microbiology, Santa Chiara Regional Hospital, 38123 Trento, Italy

⁴ Department of Laboratory Medicine, Santa Chiara Regional Hospital, 38123 Trento, Italy

⁵ Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, 50100 Florence, Italy

⁶ Klinik und Poliklinik für Urologie, Kinderurologie und Andrologie, Universitätsklinikum Giessen und Marburg GmbH, Justus-Liebig-Universität Giessen, 35390 Giessen, Germany

⁷ Department of Urology, South-Pest Hospital, 1051 Budapest, Hungary

⁸ Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE14XE, UK

⁹ Department of Urology, Skåne University Hospital, University of Lund, S-20502 Malmö, Sweden

¹⁰ Department of Urology, Oslo University Hospital, 0271 Oslo, Norway

¹¹ Department of Urology, University of Florence, 50012 Florence, Italy

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Pathogens 2016, 5(1), 4; https://doi.org/10.3390/pathogens5010004 - 5 Jan 2016

Cited by 16 | Viewed by 8694

Abstract

Asymptomatic bacteriuria (ABU) is a common clinical condition that often leads to unnecessary antimicrobial use. The reduction of antibiotic overuse for ABU is consequently an important issue for antimicrobial stewardship and to reduce the emergence of multidrug resistant strains. There are two issues [...] Read more.

Asymptomatic bacteriuria (ABU) is a common clinical condition that often leads to unnecessary antimicrobial use. The reduction of antibiotic overuse for ABU is consequently an important issue for antimicrobial stewardship and to reduce the emergence of multidrug resistant strains. There are two issues in everyday urological practice that require special attention: the role of ABU in pre-operative prophylaxis and in women affected by recurrent urinary tract infections (rUTIs). Nowadays, this is the time to think over our practice and change our way of thinking. Here, we aimed to summarize the current literature knowledge in terms of ABU management in patients undergoing urological surgery and in patients with rUTIs. In the last years, the approach to patient with ABU has changed totally. Prior to all surgical procedures that do not enter the urinary tract, ABU is generally not considered as a risk factor, and screening and treatment are not considered necessary. On the other hand, in the case of all procedures entering the urinary tract, ABU should be treated in line with the results of a urine culture obtained before the procedure. In patients affected by rUTIs, ABU can even have a protective role in preventing symptomatic recurrence, particularly when Enterococcus faecalis (E. faecalis) has been isolated. Full article

(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)

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Pathogens, Volume 5, Issue 1 (March 2016) – 33 articles

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