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Pathogens, Volume 4, Issue 3 (September 2015) – 17 articles , Pages 422-696

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Open AccessReview
Immune Response to Human Metapneumovirus Infection: What We Have Learned from the Mouse Model
Pathogens 2015, 4(3), 682-696; https://doi.org/10.3390/pathogens4030682 - 18 Sep 2015
Cited by 10 | Viewed by 3193
Abstract
Human Metapneumovirus (hMPV) is a leading respiratory viral pathogen associated with bronchiolitis, pneumonia, and asthma exacerbation in young children, the elderly and immunocompromised individuals. The development of a potential vaccine against hMPV requires detailed understanding of the host immune system, which plays a [...] Read more.
Human Metapneumovirus (hMPV) is a leading respiratory viral pathogen associated with bronchiolitis, pneumonia, and asthma exacerbation in young children, the elderly and immunocompromised individuals. The development of a potential vaccine against hMPV requires detailed understanding of the host immune system, which plays a significant role in hMPV pathogenesis, susceptibility and vaccine efficacy. As a result, animal models have been developed to better understand the mechanisms by which hMPV causes disease. Several animal models have been evaluated and established so far to study the host immune responses and pathophysiology of hMPV infection. However, inbred laboratory mouse strains have been one of the most used animal species for experimental modeling and therefore used for the studies of immunity and immunopathogenesis to hMPV. This review summarizes the contributions of the mouse model to our understanding of the immune response against hMPV infection. Full article
(This article belongs to the Special Issue Animal Model to Study Viral Immunity)
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Open AccessReview
Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model)
Pathogens 2015, 4(3), 662-681; https://doi.org/10.3390/pathogens4030662 - 16 Sep 2015
Cited by 20 | Viewed by 3162
Abstract
Chikungunya virus (CHIKV) is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and [...] Read more.
Chikungunya virus (CHIKV) is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs) serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis. Full article
(This article belongs to the Special Issue Viral Pathogenesis)
Open AccessReview
Systems Level Dissection of Candida Recognition by Dectins: A Matter of Fungal Morphology and Site of Infection
Pathogens 2015, 4(3), 639-661; https://doi.org/10.3390/pathogens4030639 - 21 Aug 2015
Cited by 12 | Viewed by 3773
Abstract
Candida albicans is an ubiquitous fungal commensal of human skin and mucosal surfaces, and at the same time a major life-threatening human fungal pathogen in immunocompromised individuals. Host defense mechanisms rely on the capacity of professional phagocytes to recognize Candida cell wall antigens. [...] Read more.
Candida albicans is an ubiquitous fungal commensal of human skin and mucosal surfaces, and at the same time a major life-threatening human fungal pathogen in immunocompromised individuals. Host defense mechanisms rely on the capacity of professional phagocytes to recognize Candida cell wall antigens. During the past decade, the host immune response to Candida was dissected in depth, highlighting the essential role of C-type lectin receptors, especially regarding the power of the Dectins’ family in discriminating between the tolerated yeast-like form of Candida and its invading counterpart, the hyphae. This review focuses on the immuno-modulatory properties of the Candida morphologies and their specific interactions with the host innate immune system in different body surfaces. Full article
(This article belongs to the Special Issue Candida Albicans Infections)
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Open AccessArticle
Molecular Detection and Characterization of Theileria Infecting Wildebeest (Connochaetes taurinus) in the Maasai Mara National Reserve, Kenya
Pathogens 2015, 4(3), 626-638; https://doi.org/10.3390/pathogens4030626 - 18 Aug 2015
Cited by 3 | Viewed by 2365
Abstract
Theileria is a genus of tick-borne protozoan that is globally widespread and infects nearly all ungulates in which they cause either latent infection or lethal disease. Wild animals are considered reservoir hosts of many species of Theileria and their diversity in wildlife species [...] Read more.
Theileria is a genus of tick-borne protozoan that is globally widespread and infects nearly all ungulates in which they cause either latent infection or lethal disease. Wild animals are considered reservoir hosts of many species of Theileria and their diversity in wildlife species is increasingly becoming of interest. The molecular characterization and identification of Theileria infecting wildlife has been studied in a few species including buffalo, which are considered reservoir host for Theileria parva infecting cattle. In this study, we sequenced Theileria species infecting wildebeest (Connochaetes taurinus) and used molecular-genetic and phylogenetic analysis of the 18 Small Subunit of the Ribosomal RNA (18S rRNA) to identify their relationships with known species of Theileria. Our results revealed three new Theileria haplotypes infecting wildebeest. Phylogenetic analysis revealed that haplotype 1 and 2 clustered in the same clade as Theileria separata and with Theileria sp. isolated from other small to medium sized antelopes. Haplotype 3 clustered close to the Theileria ovis clade. This is the first molecular description and characterization of Theileria species infecting blue wildebeest in East Africa. This study demonstrates the potential for Theileria transmission between wildebeest and small domestic ungulates, such as sheep and goats. Full article
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Open AccessArticle
In Vitro Activity of Cefepime/AAI101 and Comparators against Cefepime Non-susceptible Enterobacteriaceae
Pathogens 2015, 4(3), 620-625; https://doi.org/10.3390/pathogens4030620 - 18 Aug 2015
Cited by 19 | Viewed by 2581
Abstract
We evaluated the in vitro potency of cefepime combined with AAI101, a novel extended-spectrum β-lactamase inhibitor, against a population of clinical Escherichia coli and Klebsiella pneumoniae collected from USA hospitals. Of the 223 cefepime non-susceptible isolates, 95% were ceftazidime non-susceptible, 49% ertapenem non-susceptible, [...] Read more.
We evaluated the in vitro potency of cefepime combined with AAI101, a novel extended-spectrum β-lactamase inhibitor, against a population of clinical Escherichia coli and Klebsiella pneumoniae collected from USA hospitals. Of the 223 cefepime non-susceptible isolates, 95% were ceftazidime non-susceptible, 49% ertapenem non-susceptible, 57% piperacillin/tazobactam non-susceptible, 90% were multidrug-resistant (resistant to ≥3 drug classes), 22% produced carbapenemases, and 67% produced ESBLs. Addition of AAI101 restored the activity of cefepime such that the MIC50 was reduced from >64 mg/L for cefepime to 0.13 mg/L for cefepime/AAI101, supporting its continued development treatment for infections caused by these organisms. Full article
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Open AccessReview
Interleukin 17-Mediated Host Defense against Candida albicans
Pathogens 2015, 4(3), 606-619; https://doi.org/10.3390/pathogens4030606 - 12 Aug 2015
Cited by 34 | Viewed by 3409
Abstract
Candida albicans is part of the normal microbiota in most healthy individuals. However, it can cause opportunistic infections if host defenses are breached, with symptoms ranging from superficial lesions to severe systemic disease. The study of rare congenital defects in patients with chronic [...] Read more.
Candida albicans is part of the normal microbiota in most healthy individuals. However, it can cause opportunistic infections if host defenses are breached, with symptoms ranging from superficial lesions to severe systemic disease. The study of rare congenital defects in patients with chronic mucocutaneous candidiasis led to the identification of interleukin-17 (IL-17) as a key factor in host defense against mucosal fungal infection. Experimental infections in mice confirmed the critical role of IL-17 in mucocutaneous immunity against C. albicans. Research on mouse models has also contributed importantly to our current understanding of the regulation of IL-17 production by different cellular sources and its effector functions in distinct tissues. In this review, we highlight recent findings on IL-17-mediated immunity against C. albicans in mouse and man. Full article
(This article belongs to the Special Issue Candida Albicans Infections)
Open AccessArticle
Assessing the Surrogate Susceptibility of Oxacillin and Cefoxitin for Commonly Utilized Parenteral Agents against Methicillin-Susceptible Staphylococcus aureus: Focus on Ceftriaxone Discordance between Predictive Susceptibility and in Vivo Exposures
Pathogens 2015, 4(3), 599-605; https://doi.org/10.3390/pathogens4030599 - 30 Jul 2015
Cited by 5 | Viewed by 2287
Abstract
Susceptibility testing with the use of surrogate agents is common among clinical microbiology laboratories. One such example is oxacillin and cefoxitin for β-lactams against methicillin-susceptible Staphylococcus aureus (MSSA). This study aimed to assess the surrogate predictive value (SPV) of oxacillin and cefoxitin for [...] Read more.
Susceptibility testing with the use of surrogate agents is common among clinical microbiology laboratories. One such example is oxacillin and cefoxitin for β-lactams against methicillin-susceptible Staphylococcus aureus (MSSA). This study aimed to assess the surrogate predictive value (SPV) of oxacillin and cefoxitin for the susceptibility of commonly utilized parenteral β-lactams against MSSA as well as to evaluate the concordance between predictive susceptibility testing and the in vivo exposures for ceftriaxone. Broth microdilution MICs were determined for cefazolin, cefoxitin, ceftaroline, ceftriaxone, nafcillin, and oxacillin against a national collection of 1238 MSSA from US hospitals. Pharmacodynamic profiling was utilized to establish a clinical breakpoint for commonly utilized doses of ceftriaxone. Oxacillin had good SPVs for all the β-lactams tested, whereas cefoxitin produced unacceptable major errors for all four agents and thus appears to be an unacceptable susceptibility surrogate. While oxacillin is an adequate surrogate based on the currently defined laboratory criteria, our data also suggest that caution should be exercised when incorporating this testing approach in the clinical setting in view of the fact that the MIC distribution of MSSA coupled with the commonly utilized low doses of ceftriaxone may result in inadequate in vivo exposures against this pathogen. Full article
(This article belongs to the Special Issue Staphylococcus Aureus Infection)
Open AccessShort Communication
Opportunistic Pathogens Mycobacterium Avium Complex (MAC) and Legionella spp. Colonise Model Shower
Pathogens 2015, 4(3), 590-598; https://doi.org/10.3390/pathogens4030590 - 24 Jul 2015
Cited by 8 | Viewed by 2805
Abstract
Legionella spp. and Mycobacterium avium complex (MAC) are opportunistic pathogens of public health concern. Hot water systems, including showers, have been identified as a potential source of infection. This paper describes the colonization of Legionella and MAC on the flexible tubing within a [...] Read more.
Legionella spp. and Mycobacterium avium complex (MAC) are opportunistic pathogens of public health concern. Hot water systems, including showers, have been identified as a potential source of infection. This paper describes the colonization of Legionella and MAC on the flexible tubing within a model potable shower system, utilizing thermostatic mixing and a flexible shower head. A MAC qPCR method of enumeration was also developed. MAC and Legionella spp. were detected within the biofilm at maximum concentrations of 7.0 × 104 and 2.0 × 103 copies/cm2 PVC tubing respectively. No significant changes were observed between sample of the flexible shower tubing that dried between uses and those that remained filled with water. This suggested the “unhooking” showerheads and allowing them to dry is not an effective method to reduce the risk of Legionella or MAC colonisation. Full article
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Open AccessArticle
Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2
Pathogens 2015, 4(3), 573-589; https://doi.org/10.3390/pathogens4030573 - 24 Jul 2015
Cited by 11 | Viewed by 2844
Abstract
The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary [...] Read more.
The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2Δ/Δ mutant separates biofilm formation and invasion. We found that an rhr2Δ/Δ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2Δ/Δ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population. Full article
(This article belongs to the Special Issue Candida Albicans Infections)
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Open AccessBrief Report
Neutrophils Do Not Express IL-17A in the Context of Acute Oropharyngeal Candidiasis
Pathogens 2015, 4(3), 559-572; https://doi.org/10.3390/pathogens4030559 - 24 Jul 2015
Cited by 19 | Viewed by 3432
Abstract
IL-17 protects against pathogens by acting on nonhematopoietic cells to induce neutrophil recruitment through upregulation of chemokines and G-CSF. IL-17- and Th17-deficient humans and mice are susceptible to mucosal Candida albicans infections, linked to impaired neutrophil responses. IL-17 production is traditionally associated [...] Read more.
IL-17 protects against pathogens by acting on nonhematopoietic cells to induce neutrophil recruitment through upregulation of chemokines and G-CSF. IL-17- and Th17-deficient humans and mice are susceptible to mucosal Candida albicans infections, linked to impaired neutrophil responses. IL-17 production is traditionally associated with CD4+ Th17 cells. However, IL-17 is also expressed during innate responses to facilitate rapid pathogen clearance. Innate IL-17-expressing cells include various lymphocyte-type subsets, including ILC3, NKT, γδ-T and “natural” Th17 (nTh17) cells. Some reports suggest that neutrophils can express IL-17 during fungal infections. Here, we asked whether neutrophils serve as a source of IL-17 during acute oropharyngeal candidiasis (OPC) using an IL-17A fate-tracking reporter mouse. Mice were subjected to OPC for two days, and oral tissue was analyzed by flow cytometry. IL-17A was expressed by γδ-T cells and TCRβ+ natural Th17 (nTh17) cells, as recently reported. Although infiltrating neutrophils were recruited to the tongue following infection, they did not express the IL-17A reporter. Moreover, neutrophil-depleted mice exhibited normal transcription of both Il17a and downstream IL-17-dependent gene targets after Candida challenge. Thus, in acute OPC, neutrophils are not a measurable source of IL-17 production, nor are they necessary to trigger IL-17-dependent gene expression, although they are essential for ultimate pathogen control. Full article
(This article belongs to the Special Issue Candida Albicans Infections)
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Open AccessArticle
Experimental West Nile Virus Infection in Rabbits: An Alternative Model for Studying Induction of Disease and Virus Control
Pathogens 2015, 4(3), 529-558; https://doi.org/10.3390/pathogens4030529 - 14 Jul 2015
Cited by 11 | Viewed by 3130
Abstract
The economic impact of non-lethal human and equine West Nile virus (WNV) disease is substantial, since it is the most common presentation of the infection. Experimental infection with virulent WNV strains in the mouse and hamster models frequently results in severe neural infection [...] Read more.
The economic impact of non-lethal human and equine West Nile virus (WNV) disease is substantial, since it is the most common presentation of the infection. Experimental infection with virulent WNV strains in the mouse and hamster models frequently results in severe neural infection and moderate to high mortality, both of which are not representative features of most human and equine infections. We have established a rabbit model for investigating pathogenesis and immune response of non-lethal WNV infection. Two species of rabbits, New Zealand White (Oryctolagus cuniculus) and North American cottontail (Sylvilagus sp.), were experimentally infected with virulent WNV and Murray Valley encephalitis virus strains. Infected rabbits exhibited a consistently resistant phenotype, with evidence of low viremia, minimal-absent neural infection, mild-moderate neuropathology, and the lack of mortality, even though productive virus replication occurred in the draining lymph node. The kinetics of anti-WNV neutralizing antibody response was comparable to that commonly seen in infected horses and humans. This may be explained by the early IFNα/β and/or γ response evident in the draining popliteal lymph node. Given this similarity to the human and equine disease, immunocompetent rabbits are, therefore, a valuable animal model for investigating various aspects of non-lethal WNV infections. Full article
(This article belongs to the Special Issue Viral Pathogenesis)
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Open AccessReview
HACCP-Based Programs for Preventing Disease and Injury from Premise Plumbing: A Building Consensus
Pathogens 2015, 4(3), 513-528; https://doi.org/10.3390/pathogens4030513 - 09 Jul 2015
Cited by 10 | Viewed by 5114
Abstract
Thousands of preventable injuries and deaths are annually caused by microbial, chemical and physical hazards from building water systems. Water is processed in buildings before use; this can degrade the quality of the water. Processing steps undertaken on-site in buildings often include conditioning, [...] Read more.
Thousands of preventable injuries and deaths are annually caused by microbial, chemical and physical hazards from building water systems. Water is processed in buildings before use; this can degrade the quality of the water. Processing steps undertaken on-site in buildings often include conditioning, filtering, storing, heating, cooling, pressure regulation and distribution through fixtures that restrict flow and temperature. Therefore, prevention of disease and injury requires process management. A process management framework for buildings is the hazard analysis and critical control point (HACCP) adaptation of failure mode effects analysis (FMEA). It has been proven effective for building water system management. Validation is proof that hazards have been controlled under operating conditions and may include many kinds of evidence including cultures of building water samples to detect and enumerate potentially pathogenic microorganisms. However, results from culture tests are often inappropriately used because the accuracy and precision are not sufficient to support specifications for control limit or action triggers. A reliable negative screen is based on genus-level Polymerase Chain Reaction (PCR) for Legionella in building water systems; however, building water samples with positive results from this test require further analysis by culture methods. Full article
(This article belongs to the Special Issue Waterborne Pathogens)
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Open AccessArticle
Enumeration of Somatic and F-RNA Phages as an Indicator of Fecal Contamination in Potable Water from Rural Areas of the North West Province
Pathogens 2015, 4(3), 503-512; https://doi.org/10.3390/pathogens4030503 - 01 Jul 2015
Cited by 3 | Viewed by 2503
Abstract
Bacteriophages are regarded as enteric viral indicators in faecally contaminated water systems and may indicate the presence of human viral pollution. They are relatively resistant to inactivation by natural and treatment processes. In this study, the presence of somatic coliphages and F-RNA coliphages [...] Read more.
Bacteriophages are regarded as enteric viral indicators in faecally contaminated water systems and may indicate the presence of human viral pollution. They are relatively resistant to inactivation by natural and treatment processes. In this study, the presence of somatic coliphages and F-RNA coliphages was investigated in potable water from rural areas in the North West province. Water samples were aseptically collected from boreholes and tap water from some rural communities in the North West Province. Physical parameters of the water, such as the temperature, pH and turbidity, were measured before sample collection. Double-agar layer assay was performed using ISO, (1995, 2000) standard methods. Bottled water was used as a negative control and the strains фX174 and MS2 as positive controls. Of the 16 water samples collected, 15 were positive for somatic bacteriophages while F-RNA coliphages were detected in only two samples. Amongst the positive samples 189 and three plaque forming units were obtained for both somatic and F-RNA coliphages, respectively. No coliphage was detected in water from Masamane tap 1. The rest of the samples obtained from various rural areas were positive and did not comply with national and international standards for potable water. This was a cause for concern and should be further investigated. Full article
(This article belongs to the Special Issue Waterborne Pathogens)
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Open AccessReview
Occurrence and Control of Legionella in Recycled Water Systems
Pathogens 2015, 4(3), 470-502; https://doi.org/10.3390/pathogens4030470 - 01 Jul 2015
Cited by 24 | Viewed by 3349
Abstract
Legionella pneumophila is on the United States Environmental Protection Agency (USEPA) Candidate Contaminant list (CCL) as an important pathogen. It is commonly encountered in recycled water and is typically associated with amoeba, notably Naegleria fowleri (also on the CCL) and Acanthamoeba sp. No [...] Read more.
Legionella pneumophila is on the United States Environmental Protection Agency (USEPA) Candidate Contaminant list (CCL) as an important pathogen. It is commonly encountered in recycled water and is typically associated with amoeba, notably Naegleria fowleri (also on the CCL) and Acanthamoeba sp. No legionellosis outbreak has been linked to recycled water and it is important for the industry to proactively keep things that way. A review was conducted examine the occurrence of Legionella and its protozoa symbionts in recycled water with the aim of developing a risk management strategy. The review considered the intricate ecological relationships between Legionella and protozoa, methods for detecting both symbionts, and the efficacy of various disinfectants. Full article
(This article belongs to the Special Issue Waterborne Pathogens)
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Open AccessReview
Elimination of Bloodstream Infections Associated with Candida albicans Biofilm in Intravascular Catheters
Pathogens 2015, 4(3), 457-469; https://doi.org/10.3390/pathogens4030457 - 29 Jun 2015
Cited by 23 | Viewed by 4643
Abstract
Intravascular catheters are among the most commonly inserted medical devices and they are known to cause a large number of catheter related bloodstream infections (BSIs). Biofilms are associated with many chronic infections due to the aggregation of microorganisms. One of these organisms is [...] Read more.
Intravascular catheters are among the most commonly inserted medical devices and they are known to cause a large number of catheter related bloodstream infections (BSIs). Biofilms are associated with many chronic infections due to the aggregation of microorganisms. One of these organisms is the fungus Candida albicans. It has shown to be one of the leading causes of catheter-related BSIs. The presence of biofilm on intravascular catheters provide increased tolerance against antimicrobial treatments, thus alternative treatment strategies are sought. Traditionally, many strategies, such as application of combined antimicrobials, addition of antifungals, and removal of catheters, have been practiced, but they were not successful in eradicating BSIs. Since these fungal infections can result in significant morbidity, mortality, and increased healthcare cost, other promising preventive strategies, including antimicrobial lock therapy, chelating agents, alcohol, and biofilm disruptors, have been applied. In this review, current success and failure of these new approaches, and a comparison with the previous strategies are discussed in order to understand which preventative treatment is the most effective in controlling the catheter-related BSIs. Full article
(This article belongs to the Special Issue Candida Albicans Infections)
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Open AccessReview
Fasciola hepatica: Histology of the Reproductive Organs and Differential Effects of Triclabendazole on Drug-Sensitive and Drug-Resistant Fluke Isolates and on Flukes from Selected Field Cases
Pathogens 2015, 4(3), 431-456; https://doi.org/10.3390/pathogens4030431 - 26 Jun 2015
Cited by 16 | Viewed by 5702
Abstract
This review summarises the findings of a series of studies in which the histological changes, induced in the reproductive system of Fasciola hepatica following treatment of the ovine host with the anthelmintic triclabendazole (TCBZ), were examined. A detailed description of the normal macroscopic [...] Read more.
This review summarises the findings of a series of studies in which the histological changes, induced in the reproductive system of Fasciola hepatica following treatment of the ovine host with the anthelmintic triclabendazole (TCBZ), were examined. A detailed description of the normal macroscopic arrangement and histological features of the testes, ovary, vitelline tissue, Mehlis’ gland and uterus is provided to aid recognition of the drug-induced lesions, and to provide a basic model to inform similar toxicological studies on F. hepatica in the future. The production of spermatozoa and egg components represents the main energy consuming activity of the adult fluke. Thus the reproductive organs, with their high turnover of cells and secretory products, are uniquely sensitive to metabolic inhibition and sub-cellular disorganisation induced by extraneous toxic compounds. The flukes chosen for study were derived from TCBZ-sensitive (TCBZ-S) and TCBZ-resistant (TCBZ-R) isolates, the status of which had previously been proven in controlled clinical trials. For comparison, flukes collected from flocks where TCBZ resistance had been diagnosed by coprological methods, and from a dairy farm with no history of TCBZ use, were also examined. The macroscopic arrangement of the reproductive system in flukes was studied using catechol/carmine stained whole mounts, and the histology of the main organs was examined using conventional haematoxylin-eosin stained sections. Validation of apoptosis in the fluke sections was carried out using an in situ hybridisation method designed to label endonuclease-induced DNA strand breaks. In TCBZ-S flukes exposed to TCBZ metabolites for 24–96 h in vivo, but not in TCBZ-R flukes, those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), were found to display progressive loss of cell content. This was due to apparent failure of cell division to keep pace with expulsion of the mature or effete products. Further, actively dividing cell types tended to become individualised, rounded and condensed, characteristic of apoptotic cell death. In the treated TCBZ-S flukes, strong positive labelling indicating apoptosis was associated with the morphologically abnormal cells undergoing mitosis or meiosis in the testis, ovary and vitelline follicles. In treated flukes from field outbreaks of suspected TCBZ-R fasciolosis, no significant histological changes were observed, nor was there any positive labelling for apotosis. On the other hand, sections of TCBZ treated flukes derived from a field case of fasciolosis where TCBZ resistance was not suspected displayed severe histological lesions, and heavy positive labelling for apoptosis. The triggering of apoptosis is considered to be related to failure of spindle formation at cell division, supporting the contention that TCBZ inhibits microtubule formation. In treated TCBZ-S flukes, protein synthesis and transport was apparently inhibited in the Mehlis’ secretory cells, perhaps due to energy uncoupling or to microtubule defects. In the uterus, successful formation of shelled eggs represents the culmination of a complex sequence of cytokinetic, cytological and synthetic activity involving the vitelline follicles, the ovary and the Mehlis’ gland. Histological evidence indicating failure of ovigenesis in TCBZ-S flukes was evident from as early as 24 h post-treatment onwards. Light labelling for apoptosis was associated with the testis of untreated Cullompton (TCBZ-S) and Sligo type 2 (TCBZ-R) flukes, which exhibit abnormal spermatogenesis and spermiogenesis, respectively. This was attributed to apoptosis and to heterophagy of effete germ line cells by the sustentacular tissue. The studies summarised in this review illustrate the potential utility of histological techniques for conveniently screening representative samples of flukes in field trials designed to validate instances of drug resistance. Histology can also be used to test the efficacy of new products against known drug-resistant and drug-susceptible fluke isolates. The account also provides reference criteria for drug-induced histopathological changes in fluke reproductive structures, examination of which may supplement and augment conventional coprological testing, and aid interpretation of TEM findings. Full article
(This article belongs to the Special Issue Host-Parasite Interactions)
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Open AccessReview
Molecular Characterization of the Multidrug Resistant Escherichia coli ST131 Clone
Pathogens 2015, 4(3), 422-430; https://doi.org/10.3390/pathogens4030422 - 26 Jun 2015
Cited by 21 | Viewed by 3716
Abstract
Escherichia coli ST131 is a recently emerged and globally disseminated multidrug resistant clone associated with urinary tract and bloodstream infections in both community and clinical settings. The most common group of ST131 strains are defined by resistance to fluoroquinolones and possession of the [...] Read more.
Escherichia coli ST131 is a recently emerged and globally disseminated multidrug resistant clone associated with urinary tract and bloodstream infections in both community and clinical settings. The most common group of ST131 strains are defined by resistance to fluoroquinolones and possession of the type 1 fimbriae fimH30 allele. Here we provide an update on our recent work describing the globally epidemiology of ST131. We review the phylogeny of ST131 based on whole genome sequence data and highlight the important role of recombination in the evolution of this clonal lineage. We also summarize our findings on the virulence of the ST131 reference strain EC958, and highlight the use of transposon directed insertion-site sequencing to define genes associated with serum resistance and essential features of its large antibiotic resistance plasmid pEC958. Full article
(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)
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