Arturo Casadevall

University of Michigan, Ann Arbor, Michigan, United States

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Publications (642)3459.04 Total impact

  • Arturo Casadevall, Liise-anne Pirofski
    Nature 12/2014; 516(7530):165-6. · 42.35 Impact Factor
  • Arturo Casadevall, Liise-Anne Pirofski
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    ABSTRACT: Since proof of the germ theory of disease in the late 19(th) century a major focus of the fields of microbiology and infectious diseases has been to seek differences between pathogenic and non-pathogenic microbes and the role that the host plays in microbial pathogenesis. Remarkably, despite the increasing recognition that host immunity plays a role in microbial pathogenesis, there has been little discussion about what constitutes a host. Historically, hosts have been viewed in the context of their fitness or immunological status, and characterized by adjectives such as immune, immunocompetent, immunosuppressed, immunocompromised, or immunologically impaired. However, in recent years it has become apparent that the microbiota has profound effects on host homeostasis and susceptibility to microbial diseases in addition to its effects on host immunity. This raises the question of how to incorporate the microbiota into defining a host. This definitional problem is further complicated because neither host nor microbial properties are adequate to predict the outcome of host-microbe interaction because this outcome exhibits emergent properties. In this essay we revisit the 'damage-response framework' (DRF) of microbial pathogenesis and demonstrate how it can incorporate the rapidly accumulating information being generated by the microbiome revolution. We use the tenets of the DRF to put forth the following definition of a host: a host is an entity that houses an associated microbiome/microbiota and interacts with microbes such that the outcome results in damage, benefit, or indifference thus resulting in the states of symbiosis, colonization, commensalism, latency and disease.
    Infection and Immunity 11/2014; · 4.16 Impact Factor
  • Ekaterina Dadachova, Arturo Casadevall
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    ABSTRACT: Novel approaches to treatment of infectious diseases are urgently needed. This need has resulted in renewing the interest in antibodies for therapy of infectious diseases. Radioimmunotherapy (RIT) is a cancer treatment modality, which utilizes radiolabeled monoclonal antibodies (mAbs). During the last decade we have translated RIT into the field of experimental fungal, bacterial and HIV infections. In addition, successful proof of principle experiments with radiolabeled pan-antibodies that bind to antigens shared by major pathogenic fungi were performed in vitro. The armamentarium of pan-antibodies would result in reducing the dependence on microorganism-specific antibodies and thus would speed up the development of RIT of infections. We believe that the time is ripe for deploying RIT into the clinic to combat infectious diseases.
    Microbiology spectrum. 11/2014; 2(6):0023.
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    ABSTRACT: Review experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen (intracellular vs extracellular).•Provide evidence that antibodies contribute to the defense immune response against M. tuberculosis.•Discuss the how the multifacted B cells and humoral immunity can interact with T cells and other effector cells to shape the development of immune responses to M. tuberculosis.•Advocate for consideration a comprehensive approach that embraces both humoral and cellular immunity so as to gain better understanding of the immune response to M. tuberculosis.
    Seminars in Immunology 10/2014; · 5.93 Impact Factor
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    ABSTRACT: Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal).
    PLoS ONE 10/2014; 9(10):e111163. · 3.53 Impact Factor
  • Julie M. Wolf, Arturo Casadevall
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    ABSTRACT: Extracellular vesicles (EV) produced by eukaryotic microbes play an important role during infection. EV release is thought to benefit microbial invasion by delivering a high concentration of virulence factors to distal host cells or to the cytoplasm of a host cell. EV can significantly impact the outcome of host–pathogen interaction in a cargo-dependent manner. Release of EV from eukaryotic microbes poses unique challenges when compared to their bacterial or archaeal counterparts. Firstly, the membrane-bound organelles within eukaryotes facilitate multiple mechanisms of vesicle generation. Secondly, the fungal cell wall poses a unique barrier between the vesicle release site at the plasma membrane and its destined extracellular environment. This review focuses on these eukaryotic-specific aspects of vesicle synthesis and release.
    Current Opinion in Microbiology 10/2014; 22:73–78. · 7.22 Impact Factor
  • Jacqueline M Achkar, John Chan, Arturo Casadevall
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    ABSTRACT: Accumulating evidence has documented a role for B cells and antibodies (Abs) in the immunity against Mycobacterium tuberculosis (Mtb). Passive transfer studies with monoclonal antibodies (mAbs) against mycobacterial antigens have shown protection against the tubercle bacillus. B cells and Abs are believed to contribute to an enhanced immune response against Mtb by modulating various immunological components in the infected host including the T-cell compartment. Nevertheless, the extent and contribution of B cells and Abs to protection against Mtb remains uncertain. In this article we summarize the most relevant findings supporting the role of B cells and Abs in the defense against Mtb and discuss the potential mechanisms of protection.
    Cold Spring Harbor Perspectives in Medicine 10/2014; · 7.56 Impact Factor
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    ABSTRACT: The release of extracellular vesicles (EV) by fungal organisms is considered an alternative transport mechanism to trans-cell wall passage of macromolecules. Previous studies have revealed the presence of EV in culture supernatants from fungal pathogens, such as Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Malassezia sympodialis and Candida albicans. Here we investigated the size, composition, kinetics of internalization by bone-marrow derived murine macrophages (MO) and dendritic cells (DC), and the immunomodulatory activity of C. albicans EV. We also evaluated the impact of EVs on fungal virulence using the Galleria mellonella larvae model. By transmission electron microscopy and dynamic light scattering we identified two populations ranging from 50-100 and 350-850 nm. Two predominant seroreactive proteins (27 and 37 kDa) and a group of polydispersed mannoproteins were observed in EV by immunoblotting analysis. Proteomic analysis of C. albicans EV revealed proteins related to pathogenesis, cell organization, carbohydrate and lipid metabolism, response to stress and several other functions. The major lipids detected by thin layer chromatography were ergosterol, lanosterol and glucosylceramide. Short exposure of MO to EV resulted in internalization of these vesicles and production of nitric oxide, IL-12, TGF-β and IL-10. Similarly, EV-treated DC produced IL- 12p40, IL-10 and TNF-α. In addition, EV treatment induced the upregulation of CD86 and MHC-II. Inoculation of G. mellonella larvae with EV followed by challenge with C. albicans reduced the number of recovered viable yeasts in comparison to infected larvae control. Taking together, our results demonstrate that C. albicans EV were immunologically active and could potentially interfere with the host responses in the setting of invasive candidiasis.
    Cellular Microbiology 10/2014; · 4.82 Impact Factor
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    ABSTRACT: Pathogenic and nonpathogenic species of bacteria and fungi release membrane vesicles (MV), containing proteins, polysaccharides, and lipids, into the extracellular milieu. Previously, we demonstrated that several mycobacterial species, including bacillus Calmette-Guerin (BCG) and Mycobacterium tuberculosis, release MV containing lipids and proteins that subvert host immune response in a Toll-like receptor 2 (TLR2)-dependent manner (R. Prados-Rosales et al., J. Clin. Invest. 121:1471-1483, 2011, doi:10.1172/JCI44261). In this work, we analyzed the vaccine potential of MV in a mouse model and compared the effects of immunization with MV to those of standard BCG vaccination. Immunization with MV from BCG or M. tuberculosis elicited a mixed humoral and cellular response directed to both membrane and cell wall components, such as lipoproteins. However, only vaccination with M. tuberculosis MV was able to protect as well as live BCG immunization. M. tuberculosis MV boosted BCG vaccine efficacy. In summary, MV are highly immunogenic without adjuvants and elicit immune responses comparable to those achieved with BCG in protection against M. tuberculosis.
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    ABSTRACT: The number of retracted scientific articles has been increasing. Most retractions are associated with research misconduct, entailing financial costs to funding sources and damage to the careers of those committing misconduct. We sought to calculate the magnitude of these effects. Data relating to retracted manuscripts and authors found by the Office of Research Integrity (ORI) to have committed misconduct were reviewed from public databases. Attributable costs of retracted manuscripts, and publication output and funding of researchers found to have committed misconduct were determined. We found that papers retracted due to misconduct accounted for approximately $58 million in direct funding by the NIH between 1992 and 2012, less than 1% of the NIH budget over this period. Each of these articles accounted for a mean of $392,582 in direct costs (SD $423,256). Researchers experienced a median 91.8% decrease in publication output and large declines in funding after censure by the ORI.DOI: http://dx.doi.org/10.7554/eLife.02956.001.
    eLife Sciences 08/2014; 3:e02956. · 8.52 Impact Factor
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    ABSTRACT: Despite the essential functions of melanin pigments in diverse organisms and their roles in inspiring designed nanomaterials for electron transport and drug delivery, the structural frameworks of the natural materials and their biomimetic analogs remain poorly understood. To overcome the investigative challenges posed by these insoluble heterogeneous pigments, we have used l-tyrosine or dopamine enriched with stable (13)C and (15)N isotopes to label eumelanins metabolically in cell-free and Cryptococcus neoformans cell systems and to define their molecular structures and supramolecular architectures. Using high-field two-dimensional solid-state nuclear magnetic resonance (NMR), our study directly evaluates the assumption of structural commonality between synthetic melanin models and the corresponding natural pigments, demonstrating a common indole-based aromatic core in the products from contrasting synthetic protocols for the first time.
    Organic & Biomolecular Chemistry 07/2014; · 3.49 Impact Factor
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    Arturo Casadevall, Michael J Imperiale
    mBio 07/2014; 5(4). · 6.88 Impact Factor
  • Arturo Casadevall, R Grant Steen, Ferric C Fang
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    ABSTRACT: Retraction of flawed articles is an important mechanism for correction of the scientific literature. We recently reported that the majority of retractions are associated with scientific misconduct. In the current study, we focused on the subset of retractions for which no misconduct was identified, in order to identify the major causes of error. Analysis of the retraction notices for 423 articles indexed in PubMed revealed that the most common causes of error-related retraction are laboratory errors, analytical errors, and irreproducible results. The most common laboratory errors are contamination and problems relating to molecular biology procedures (e.g., sequencing, cloning). Retractions due to contamination were more common in the past, whereas analytical errors are now increasing in frequency. A number of publications that have not been retracted despite being shown to contain significant errors suggest that barriers to retraction may impede correction of the literature. In particular, few cases of retraction due to cell line contamination were found despite recognition that this problem has affected numerous publications. An understanding of the errors leading to retraction can guide practices to improve laboratory research and the integrity of the scientific literature. Perhaps most important, our analysis has identified major problems in the mechanisms used to rectify the scientific literature and suggests a need for action by the scientific community to adopt protocols that ensure the integrity of the publication process.-Casadevall, A., Steen, R. G., Fang, F. C. Sources of error in the retracted scientific literature.
    The FASEB Journal 06/2014; · 5.48 Impact Factor
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    ABSTRACT: Cryptococcus neoformans produces extracellular vesicles containing a variety of cargo, including virulence factors. To become extracellular, these vesicles must not only be released from the plasma membrane, but also pass through the dense matrix of the cell wall. The greatest unknown in the area of fungal vesicles is the mechanism by which these vesicles are released to the extracellular space given the presence of the fungal cell wall. Here we used electron microscopy techniques to image the interactions of vesicles with the cell wall. Our goal was to define the ultrastructural morphology of the process to gain insights into the mechanisms involved. We describe single and multiple vesicle leaving events, which we hypothesized were due to plasma membrane and multivesicular body vesicle origins, respectively. We further utilized melanized cells to "trap" vesicles and visualize those passing through the cell wall. Vesicle size differed depending on whether vesicles left the cytoplasm in single versus multiple release events. Furthermore, we analyzed different vesicle populations for vesicle dimensions and protein composition. Proteomic analysis tripled the number of proteins known to be associated with vesicles. Despite separation of vesicles into batches differing in size, we did not identify major differences in protein composition. In summary, our results indicate that vesicles are generated by more than one mechanism, that vesicles exit the cell by traversing the cell wall, and that vesicle populations exist as a continuum with regards to size and protein composition.
    Eukaryotic Cell 06/2014; · 3.18 Impact Factor

Publication Stats

20k Citations
3,459.04 Total Impact Points

Institutions

  • 2014
    • University of Michigan
      • Department of Microbiology and Immunology
      Ann Arbor, Michigan, United States
  • 1990–2014
    • Albert Einstein College of Medicine
      • • Department of Pediatrics
      • • Department of Microbiology & Immunology
      • • Nuclear Medicine
      • • Department of Medicine
      • • Infectious Diseases
      • • Department of Cell Biology
      New York City, New York, United States
  • 2013
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
    • University of Brasília
      • Department of Cell Biology
      Brasília, Federal District, Brazil
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 2008–2013
    • University of Washington Seattle
      • Department of Medicine
      Seattle, WA, United States
    • Instituto Evandro Chagas
      Ananindeua, Pará, Brazil
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • Montefiore Medical Center
      • Department of Pediatrics
      New York City, NY, United States
    • Institute for Transuranium Elements
      Carlsruhe, Baden-Württemberg, Germany
    • City University of New York - Bronx Community College
      New York City, New York, United States
    • Farmingdale State College
      East Farmingdale, New York, United States
  • 2007–2013
    • Federal University of Rio de Janeiro
      • • Instituto de Microbiologia Professor Paulo de Góes (IMPPG)
      • • Instituto de Biologia (IB)
      Rio de Janeiro, Rio de Janeiro, Brazil
    • Trinity University of Asia
      Alfonso XIII, Mimaropa, Philippines
    • Trinity University
      • Department of Mathematics
      San Antonio, TX, United States
  • 2006–2013
    • Yeshiva University
      • • Department of Microbiology & Immunology
      • • Division of Infectious Diseases
      • • Division of Nuclear Medicine
      New York City, New York, United States
  • 1998–2013
    • Università degli Studi di Perugia
      • Department of Clinical and Experimental Medicine
      Terni, Umbria, Italy
    • University of Nevada School of Medicine
      Reno, Nevada, United States
  • 2012
    • Istituto Superiore di Sanità
      Roma, Latium, Italy
    • AECOM
      Sandy City, Utah, United States
    • University of Coimbra
      • Faculty of Medicine
      Coímbra, Coimbra, Portugal
  • 2011–2012
    • CUNY Graduate Center
      New York City, New York, United States
    • City University of New York - Brooklyn College
      Brooklyn, New York, United States
    • City University of New York - Bernard M. Baruch College
      • Department of Natural Sciences
      New York City, NY, United States
    • Medical University of South Carolina
      • Department of Biochemistry and Molecular Biology (College of Medicine)
      Charleston, SC, United States
    • Universidade Federal do Rio Grande do Sul
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
    • Savannah River National Laboratory
      Aiken, South Carolina, United States
  • 2010–2012
    • The Commonwealth Medical College
      • Department of Basic Sciences
      Scranton, PA, United States
  • 2008–2011
    • Instituto de Salud Carlos III
      • Center National of Microbiology (CNM)
      Madrid, Madrid, Spain
  • 2009
    • Centraalbureau voor Schimmelcultures
      Utrecht, Utrecht, Netherlands
  • 2006–2009
    • Department of Nuclear Medicine
      Nyitra, Nitriansky, Slovakia
  • 1993–2009
    • Stony Brook University
      • Department of Medicine
      Stony Brook, NY, United States
  • 2003–2008
    • City University of New York - College of Staten Island
      • Chemistry
      New York City, NY, United States
  • 1999–2008
    • Cornell University
      • • Department of Biological and Environmental Engineering
      • • Department of Pharmacology
      Ithaca, NY, United States
    • New York State
      New York City, New York, United States
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
  • 2005
    • University of British Columbia - Vancouver
      • Biomedical Research Centre (BRC)
      Vancouver, British Columbia, Canada
    • Stockholm University
      • Department of Organic Chemistry
      Stockholm, Stockholm, Sweden
    • Massachusetts General Hospital
      • Division of Infectious Diseases
      Boston, Massachusetts, United States
  • 2004
    • All India Institute of Medical Sciences
      • Department of Microbiology
      New Delhi, NCT, India
  • 2000–2003
    • Duke University Medical Center
      • • Division of Infectious Diseases
      • • Department of Medicine
      Durham, NC, United States
  • 2002
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
  • 2001
    • The University of Manchester
      Manchester, England, United Kingdom
    • Long Island University
      • Department of Biology
      New York City, NY, United States
  • 1995–1998
    • Georgia State University
      • Department of Chemistry
      Atlanta, Georgia, United States
  • 1997
    • University of Oklahoma Health Sciences Center
      • Department of Microbiology and Immunology
      Oklahoma City, OK, United States