scholarly journals Murine Models of Candida Gastrointestinal Colonization and Dissemination

2013 ◽  
Vol 12 (11) ◽  
pp. 1416-1422 ◽  
Author(s):  
Andrew Y. Koh
Keyword(s):  
Infectious Agents ◽  
Murine Models ◽  
Gi Tract ◽  
Future Directions ◽  
Content Type ◽  
Animal Modeling ◽  
Mucosal Surfaces ◽  
Modeling Systems ◽  
Human Infections ◽  
Gastrointestinal Colonization

ABSTRACTNinety-five percent of infectious agents enter through exposed mucosal surfaces, such as the respiratory and gastrointestinal (GI) tracts. The human GI tract is colonized with trillions of commensal microbes, including numerousCandidaspp. Some commensal microbes in the GI tract can cause serious human infections under specific circumstances, typically involving changes in the gut environment and/or host immune conditions. Therefore, utilizing animal models of fungal GI colonization and dissemination can lead to significant insights into the complex pathophysiology of transformation from a commensal organism to a pathogen and host-pathogen interactions. This paper will review the methodologic approaches used for modeling GI colonization versus dissemination, the insights learned from these models, and finally, possible future directions using these animal modeling systems.

scholarly journals CX3CR1 Is Dispensable for Control of Mucosal Candida albicans Infections in Mice and Humans

2014 ◽  
Vol 83 (3) ◽  
pp. 958-965 ◽  
Author(s):  
Timothy J. Break ◽  
Martin Jaeger ◽  
Norma V. Solis ◽  
Scott G. Filler ◽  
Carlos A. Rodriguez ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Human Population ◽  
Systemic Candidiasis ◽  
Gi Tract ◽  
Content Type ◽  
Commensal Microbiota ◽  
Interleukin 17A ◽  
Mucosal Surfaces ◽  
Bacterial Microbiota ◽  
Mucosal Candidiasis

Candida albicansis part of the normal commensal microbiota of mucosal surfaces in a large percentage of the human population. However, perturbations of the host's immune response or bacterial microbiota have been shown to predispose individuals to the development of opportunisticCandidainfections. It was recently discovered that a defect in the chemokine receptor CX3CR1 increases susceptibility of mice and humans to systemic candidiasis. However, whether CX3CR1 confers protection against mucosalC. albicansinfection has not been investigated. Using two different mouse models, we found that Cx3cr1 is dispensable for the induction of interleukin 17A (IL-17A), IL-22, and IL-23 in the tongue after infection, as well as for the clearance of mucosal candidiasis from the tongue or lower gastrointestinal (GI) tract colonization. Furthermore, the dysfunctional human CX3CR1 alleleCX3CR1-M280was not associated with development of recurrent vulvovaginal candidiasis (RVVC) in women. Taken together, these data indicate that CX3CR1 is not essential for protection of the host against mucosal candidiasis, underscoring the dependence on different mammalian immune factors for control of mucosal versus systemicCandidainfections.

scholarly journals Candida albicanswhite and opaque cells exhibit distinct spectra of organ colonization in mouse models of infection

2018 ◽  
Author(s):  
Julie Takagi ◽  
Sheena D. Singh-Babak ◽  
Matthew B. Lohse ◽  
Chiraj K. Dalal ◽  
Alexander D. Johnson
Keyword(s):  
Candida Albicans ◽  
Animal Studies ◽  
Murine Models ◽  
Gi Tract ◽  
Internal Organs ◽  
Mucosal Surfaces ◽  
Default State ◽  
Serious Disease ◽  
First Time ◽  
Organ Colonization

AbstractCandida albicans, a species of fungi, can thrive in diverse niches of its mammalian hosts; it is a normal resident of the GI tract and mucosal surfaces but it can also enter the bloodstream and colonize internal organs causing serious disease. The ability ofC. albicansto thrive in these different host environments has been attributed, at least in part, to its ability to assume different morphological forms. In this work, we examine one such morphological change known as white-opaque switching. White cells are the default state ofC. albicans, and most animal studies have been carried out exclusively with white cells. Here, we compared the proliferation of white and opaque cells in two murine models of infection and also monitored, using specially constructed strains, switching between the two states in the host. We found that white cells outcompeted opaque cells in many niches; however, we show for the first time that in some organs (specifically, the heart and spleen), opaque cells competed favorably with white cells and, when injected on their own, could colonize these organs. In environments where the introduced white cells outcompeted the introduced opaque cells, we observed high rates of opaque-to-white switching. We did not observe white-to-opaque switching in any of the niches we examined.

scholarly journals Acinetobacter baumanniiGastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Patrick M. Ketter ◽  
Jieh-Juen Yu ◽  
M. Neal Guentzel ◽  
Holly C. May ◽  
Rishein Gupta ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Military Personnel ◽  
Multidrug Resistant ◽  
Immune Defense ◽  
World Health ◽  
Secretory Iga ◽  
Gi Tract ◽  
Content Type ◽  
Gut Colonization ◽  
Mucosal Surfaces

ABSTRACTMultidrug-resistantAcinetobacter baumanniiis among the most common causes of infectious complications associated with combat-related trauma in military personnel serving overseas. However, little is currently known about its pathogenesis. While the gastrointestinal (GI) tract has been found to be a major reservoir forA. baumannii, as well as to potentially contribute to development of multidrug resistance, no studies have addressed the mechanisms involved in gut colonization. In this study, we address this critical gap in knowledge by first assessing the interaction between secretory IgA (SIgA), the principal humoral immune defense on mucosal surfaces, and theA. baumanniiclinical isolate Ci79. Surprisingly, SIgA appeared to enhanceA. baumanniiGI tract colonization, in a process mediated by bacterial thioredoxin A (TrxA), as evidenced by reduction of bacterial attachment in the presence of TrxA inhibitors. Additionally, atrxAtargeted deletion mutant (ΔtrxA) showed reduced bacterial burdens within the GI tract 24 h after oral challenge byin vivolive imaging, along with loss of thiol-reductase activity. Surprisingly, not only was GI tract colonization greatly reduced but the associated 50% lethal dose (LD50) of theΔtrxAmutant was increased nearly 100-fold in an intraperitoneal sepsis model. These data suggest that TrxA not only mediatesA. baumanniiGI tract colonization but also may contribute to pathogenesis inA. baumanniisepsis following escape from the GI tract under conditions when the intestinal barrier is compromised, as occurs with cases of severe shock and trauma.IMPORTANCEAcinetobacter baumanniiis an emerging bacterial pathogen recently classified as a serious threat to U.S. and global health by both the Centers for Disease Control and Prevention and the World Health Organization. It also is one of the leading causes of combat-related infections associated with injured military personnel serving overseas. Little is known regarding mechanisms of gastrointestinal tract colonization despite this site being shown to serve as a reservoir for multidrug-resistant (MDR)A. baumanniiisolates. Here, we establish that secretory IgA, the major immunoglobulin of mucosal surfaces, promotesA. baumanniiGI tract colonization via bacterial thioredoxin A as evidenced through significant reduction in colonization in IgA-deficient animals. Additionally, bacterial colonization and mortality were significantly reduced in animals challenged with a thioredoxin A-deficientA. baumanniimutant. Combined, these data suggest that thioredoxin A is a novel virulence factor, for which antithioredoxin therapies could be developed, for this important multidrug-resistant pathogen.

scholarly journals Altered Innate Defenses in the Neonatal Gastrointestinal Tract in Response to Colonization by Neuropathogenic Escherichia coli

2013 ◽  
Vol 81 (9) ◽  
pp. 3264-3275 ◽  
Author(s):  
George M. H. Birchenough ◽  
Malin E. V. Johansson ◽  
Richard A. Stabler ◽  
Fatma Dalgakiran ◽  
Gunnar C. Hansson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Systemic Infection ◽  
Developmental Expression ◽  
Gi Tract ◽  
Content Type ◽  
Rat Pups ◽  
Genes Encoding ◽  
Small Intestinal ◽  
Mucus Barrier ◽  
Gastrointestinal Colonization

ABSTRACTTwo-day-old (P2), but not 9-day-old (P9), rat pups are susceptible to systemic infection following gastrointestinal colonization byEscherichia coliK1. Age dependency reflects the capacity of colonizing K1 to translocate from gastrointestinal (GI) tract to blood. A complex GI microbiota developed by P2, showed little variation over P2 to P9, and did not prevent stable K1 colonization. Substantial developmental expression was observed over P2 to P9, including upregulation of genes encoding components of the small intestinal (α-defensins Defa24 and Defa-rs1) and colonic (trefoil factor Tff2) mucus barrier. K1 colonization modulated expression of these peptides: developmental expression of Tff2 was dysregulated in P2 tissues and was accompanied by a decrease in mucin Muc2. Conversely, α-defensin genes were upregulated in P9 tissues. We propose that incomplete development of the mucus barrier during early neonatal life and the capacity of colonizing K1 to interfere with mucus barrier maturation provide opportunities for neuropathogen translocation into the bloodstream.

scholarly journals Enterococcus faecalis Manganese Exporter MntE Alleviates Manganese Toxicity and Is Required for Mouse Gastrointestinal Colonization

2020 ◽  
Vol 88 (6) ◽  
Author(s):  
Ling Ning Lam ◽  
Jun Jie Wong ◽  
Kelvin Kian Long Chong ◽  
Kimberly A. Kline
Keyword(s):  
Enterococcus Faecalis ◽  
Gi Tract ◽  
Biofilm Growth ◽  
Mn Toxicity ◽  
Content Type ◽  
Excess Iron ◽  
Catabolic Genes ◽  
Gastrointestinal Colonization ◽  
Excess Fe

ABSTRACT Bacterial pathogens encounter a variety of nutritional environments in the human host, including nutrient metal restriction and overload. Uptake of manganese (Mn) is essential for Enterococcus faecalis growth and virulence; however, it is not known how this organism prevents Mn toxicity. In this study, we examine the role of the highly conserved MntE transporter in E. faecalis Mn homeostasis and virulence. We show that inactivation of mntE results in growth restriction in the presence of excess Mn, but not other metals, demonstrating its specific role in Mn detoxification. Upon growth in the presence of excess Mn, an mntE mutant accumulates intracellular Mn, iron (Fe), and magnesium (Mg), supporting a role for MntE in Mn and Fe export and a role for Mg in offsetting Mn toxicity. Growth of the mntE mutant in excess Fe also results in increased levels of intracellular Fe, but not Mn or Mg, providing further support for MntE in Fe efflux. Inactivation of mntE in the presence of excess iron also results in the upregulation of glycerol catabolic genes and enhanced biofilm growth, and addition of glycerol is sufficient to augment biofilm growth for both the mntE mutant and its wild-type parental strain, demonstrating that glycerol availability significantly enhances biofilm formation. Finally, we show that mntE contributes to colonization of the antibiotic-treated mouse gastrointestinal (GI) tract, suggesting that E. faecalis encounters excess Mn in this niche. Collectively, these findings demonstrate that the manganese exporter MntE plays a crucial role in E. faecalis metal homeostasis and virulence.

A bibliographic study on big data: concepts, trends and challenges

2017 ◽  
Vol 23 (3) ◽  
pp. 555-573 ◽  
Author(s):  
Deepa Mishra ◽  
Zongwei Luo ◽  
Shan Jiang ◽  
Thanos Papadopoulos ◽  
Rameshwar Dubey
Keyword(s):  
Big Data ◽  
Citation Analysis ◽  
Design Methodology ◽  
Future Directions ◽  
Content Type ◽  
Current Trends ◽  
Bibliographic Study

Purpose The purpose of paper is twofold. First, it provides a consolidated overview of the existing literature on “big data” and second, it presents the current trends and opens up various future directions for researchers who wish to explore and contribute in this rapidly evolving field. Design/methodology/approach To achieve the objective of this study, the bibliographic and network techniques of citation and co-citation analysis was adopted. This analysis involved an assessment of 57 articles published over a period of five years (2011-2015) in ten selected journals. Findings The findings reveal that the number of articles devoted to the study of “big data” has increased rapidly in recent years. Moreover, the study identifies some of the most influential articles of this area. Finally, the paper highlights the new trends and discusses the challenges associated with big data. Research limitations/implications This study focusses only on big data concepts, trends, and challenges and excludes research on its analytics. Thus, researchers may explore and extend this area of research. Originality/value To the knowledge of the authors, this is the first study to review the literature on big data by using citation and co-citation analysis.

Value co-creation: a review of literature and future research agenda

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Victor Saha ◽  
Praveen Goyal ◽  
Charles Jebarajakirthy
Keyword(s):  
Systematic Review ◽  
Future Research ◽  
Review Of Literature ◽  
Relevant Research ◽  
Research Papers ◽  
Future Directions ◽  
Content Type ◽  
Extant Literature ◽  
Future Research Agenda ◽  
Theoretical Perspectives

Purpose The purpose of this paper is to present a systematic review of the available literature on value co-creation (VCC) and provide insightful future directions for research in this domain. Design/methodology/approach The extant literature on VCC has been reviewed by collecting relevant research papers based on certain specified delimiting criteria. A total of 110 research papers have been analysed to gain useful insights into VCC literature. Findings The study analyses the literature on VCC and provides a clear distinction between VCC and its closely related constructs in the literature. The study also draws significant insights from the VCC literature based on some specific parameters. Some frequently used theoretical perspectives have been discussed in the study, thus pointing towards a few alternative theories that can be used for future research. Finally, specific trends emerging from the literature have been discussed that provide a comprehensive understanding of the research inclinations of this concept, along with future scopes of research in the VCC domain. Research limitations/implications The papers were selected for this study based on some delimiting criteria. Thus, the findings cannot be generalised for the entire research on VCC. Originality/value This paper fulfils the need for a systematic review of the extant literature on VCC. The study synthesises literature and bibliography on VCC from 2004 to 2019 to benefit both academics and practitioners and gives some directions to advance this domain of literature.

scholarly journals Activity of Debio1452, a FabI Inhibitor with Potent Activity against Staphylococcus aureus and Coagulase-Negative Staphylococcus spp., Including Multidrug-Resistant Strains

2015 ◽  
Vol 59 (5) ◽  
pp. 2583-2587 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Nachum Kaplan ◽  
Ronald N. Jones ◽  
David J. Farrell
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Fatty Acid Biosynthesis ◽  
Multidrug Resistant ◽  
Coagulase Negative Staphylococcus ◽  
Significant Activity ◽  
Coagulase Negative Staphylococci ◽  
Content Type ◽  
Mrsa Strains ◽  
Human Infections

ABSTRACTStaphylococcus aureusand coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human infections. The investigational antibacterial Debio1450 (previously AFN-1720), a prodrug of Debio1452 (previously AFN-1252), specifically targets staphylococci without significant activity against other Gram-positive or Gram-negative species. Debio1452 inhibits FabI, an enzyme critical to fatty acid biosynthesis in staphylococci. The activity of Debio1452 against CoNS, methicillin-susceptibleS. aureus(MSSA), and methicillin-resistantS. aureus(MRSA), including significant clones, was determined. A globally diverse collection of 574 patient isolates from 35 countries was tested that included CoNS (6 species, 103 strains), MSSA (154 strains), MRSA (163 strains), and molecularly characterized strains (includingspa-typed MRSA clones; 154 strains). The isolates were tested for susceptibility by CLSI broth microdilution methods against Debio1452 and 10 comparators. The susceptibility rates for the comparators were determined using CLSI and EUCAST breakpoint criteria. AllS. aureusand CoNS strains were inhibited by Debio1452 concentrations of ≤0.12 and ≤0.5 μg/ml, respectively. The MIC50s for MSSA, MRSA, and molecularly characterized MRSA strains were 0.004 μg/ml, and the MIC90s ranged from 0.008 to 0.03 μg/ml. The MICs were higher for the CoNS isolates (MIC50/90, 0.015/0.12 μg/ml). AmongS. aureusstrains, resistance was common for erythromycin (61.6%), levofloxacin (49.0%), clindamycin (27.6%), tetracycline (15.7%), and trimethoprim-sulfamethoxazole (7.0%). Debio1452 demonstrated potent activity against MSSA, MRSA, and CoNS. Debio1452 showed significantly greater activity overall (MIC50, 0.004 μg/ml) than the other agents tested against these staphylococcal species, which included dominant MRSA clones and strains resistant to currently utilized antimicrobial agents.

scholarly journals Are In Vitro Susceptibilities to Azole Antifungals Predictive of Clinical Outcome in the Treatment of Candidemia?

2018 ◽  
Vol 56 (12) ◽  
Author(s):  
Twisha S. Patel ◽  
Peggy L. Carver ◽  
Gregory A. Eschenauer
Keyword(s):  
Invasive Candidiasis ◽  
Randomized Trials ◽  
Published Data ◽  
Murine Models ◽  
Limited Data ◽  
Content Type ◽  
Clinical Breakpoints ◽  
The Impact ◽  
The Relationship

ABSTRACT The purpose of this review is to critically analyze published data evaluating the impact of azole pharmacokinetic and pharmacodynamic parameters, MICs, and Candida species on clinical outcomes in patients with candidemia. Clinical breakpoints (CBPs) for fluconazole and voriconazole, which are used to determine susceptibility, have been defined by the Clinical and Laboratory Standards Institute (CLSI) for Candida species. Studies evaluating the relationship between treatment efficacy and in vitro susceptibility, as well as the pharmacodynamic targets, have been conducted in patients treated with fluconazole for candidemia; however, for species other than Candida albicans and Candida glabrata, and for other forms of invasive candidiasis, data remain limited and randomized trials are not available. Limited data evaluating these relationships with voriconazole are available. While pharmacodynamic targets for posaconazole and isavuconazole have been proposed based upon studies conducted in murine models, CBPs have not been established by CLSI. Fluconazole remains an important antifungal agent for the treatment of candidemia, and data supporting its use based on in vitro susceptibility are growing, particularly for C. albicans and C. glabrata. Further investigation is needed to establish the roles of voriconazole, posaconazole, and isavuconazole in the treatment of candidemia and for all agents in the treatment of other forms of invasive candidiasis.

scholarly journals Extending McKinsey’s 7S model to understand strategic alignment in academic libraries

2019 ◽  
Vol 40 (5) ◽  
pp. 313-326 ◽  
Author(s):  
Andrew Martin Cox ◽  
Stephen Pinfield ◽  
Sophie Rutter
Keyword(s):  
Academic Libraries ◽  
Academic Library ◽  
Theoretical Work ◽  
Perceived Barriers ◽  
Future Directions ◽  
Content Type ◽  
Institutional Influences ◽  
Potential Applications ◽  
Strategic Position ◽  
Practical Implications

Purpose The purpose of this paper is to conceptualise the issues of alignment for changing academic libraries by using and extending McKinsey’s 7S model. Design/methodology/approach Theoretical work was conducted to consider and extend the 7S model for the situation of academic libraries. Empirical data were then used to confirm the value of these extensions and suggest further changes. The data to support the analysis were drawn from 33 interviews with librarians, library and non-library academics and experts, and a survey of UK library staff. Findings In the academic library context, the 7S model can be usefully extended to include three library functions (stuff, space and services) and users. It can also include institutional influences and stakeholders, and aspects of the external environment or situation, including suppliers and allies. The revised model then provides a useful framework within which data about library change can be analysed. Perceived barriers to successful performance fit the model and enable the identification of seven challenges of alignment. Research limitations/implications The resulting model has potential applications such as in the structuring analysis of academic library performance, mapping future directions of development and for exploring variations across the sector and internationally. Practical implications The revised model can be used by practitioners to think through their own strategic position and to act to shape their future, in the light of seven major areas of alignment. Originality/value The paper extends a well-known model used in strategy, to produce a more comprehensive, sector-specific analytic tool.

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