Arturo Casadevall

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States

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Publications (708)3594.36 Total impact

  • Alena Janda · Anthony Bowen · Neil S. Greenspan · Arturo Casadevall
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    ABSTRACT: The adaptive humoral immune response is responsible for the generation of antimicrobial proteins known as immunoglobulin molecules or antibodies. Immunoglobulins provide a defense system against pathogenic microbes and toxins by targeting them for removal and/or destruction. Historically, antibodies have been thought to be comprised of distinct structural domains known as the variable and constant regions that are responsible for antigen binding and mediating effector functions such as opsonization and complement activation, respectively. These domains were thought to be structurally and functionally independent. Recent work has revealed however, that in some families of antibodies, the two regions can influence each other. We will discuss the body of work that led to these observations, as well as the mechanisms that have been proposed to explain how these two different antibody regions may interact in the function of antigen binding.
    No preview · Article · Feb 2016 · Frontiers in Microbiology
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    Full-text · Dataset · Dec 2015
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    Full-text · Dataset · Dec 2015
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    ABSTRACT: The importance of Alternaria sp. fungi to human health ranges from being etiological agents of serious infections with poor prognosis in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, as a model organism of the genus, and was designed to unravel melanin production in the response to antifungals. After the characterization of the pigment produced by A. infectoria, we studied the dynamics of dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected the susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in the cell walls in response to nikkomycin Z, caspofungin and itraconazole but not in response to fluconazole or amphotericin B. These results indicated that A. infectoria activates DHN-melanin synthesis in response to certain fungal drugs, possibly as a protective mechanism against antifungal drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin, with enhanced morphological changes (increased balloon size) characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs and its susceptibility is influenced by melanization suggesting a therapeutic potential to drug combinations that affect melanin synthesis.
    No preview · Article · Dec 2015 · Antimicrobial Agents and Chemotherapy
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    Joshua D. Nosanchuk · Ruth E. Stark · Arturo Casadevall
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    ABSTRACT: The production of melanin significantly enhances the virulence of many important human pathogenic fungi. Despite fungal melanin’s importance in human disease, as well as melanin’s contribution to the ability of fungi to survive in diverse hostile environments, the structure of melanin remains unsolved. Nevertheless, ongoing research efforts have progressively revealed several notable structural characteristics of this enigmatic pigment, which will be the focus of this review. These compositional and organizational insights could further our ability to develop novel therapeutic approaches to combat fungal disease and enhance our understanding of how melanin is inserted into the cell wall.
    Full-text · Article · Dec 2015 · Frontiers in Microbiology
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    Liise-anne Pirofski · Arturo Casadevall
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    ABSTRACT: Proof of the Germ theory of disease and acceptance of Koch's postulates in the late 1890's launched the fields of microbial pathogenesis and infectious diseases and provided the conceptual framework that has guided thought and research in these fields. A central tenet that emerged from studies with microbes that fulfilled Koch's postulates was that microbes that caused disease had characteristics that allowed them to do so, with the corollary that microbes that did not cause disease lacked disease-causing determinants. This observation, which held true for many diseases that were known to cause disease in the late 19th century, such as toxin-producing and encapsulated bacteria, led to the view that the ability to cause disease rested with microbes and reflected the activity of specific determinants, or virulence factors. With the dawn of the 20th century, efforts to neutralize virulence factors were under development and ultimately translated into anti-microbial therapy in the form of antibodies targeted to toxins and polysaccharide capsules. However, the 20th century progressed, antibiotics were identified and developed as therapy for infectious diseases while other medical advances, such as specialized surgeries, intensive care units, intravenous catheters, and cytotoxic chemotherapy became commonplace in resourced nations. An unintended consequence of many of these advances was that they resulted in immune impairment. Similarly, HIV/AIDS, which emerged in the late 1970's also produced profound immune impairment. Unexpectedly, the prevailing view that microbes were the sole perpetrators of virulence was untenable. Microbes that were rarely if ever associated with disease emerged as major causes of disease in people with impaired immunity. This phenomenon revealed that available explanations for microbial infectiveness and virulence were flawed. In this review, we discuss the question 'what is infectiveness' based on the tenets of the Damage-response framework.
    Preview · Article · Dec 2015 · BMC Immunology
  • Anthony Bowen · Arturo Casadevall

    No preview · Article · Nov 2015 · Proceedings of the National Academy of Sciences
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    Ferric C. Fang · Arturo Casadevall

    Preview · Article · Nov 2015 · Infection and Immunity
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    Arturo Casadevall · Ferric C. Fang
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    ABSTRACT: The journal impact factor (IF) exerts a tremendous influence on the conduct of scientists. The obsession with IF has been compared to a medical condition, sometimes referred to as “IF mania” or “impactitis.” Here, we analyze the difference between impact and importance, using examples from the history of science to show that these are not equivalent. If impact does not necessarily equal importance, but scientists are focused on high-impact work, there is a danger that misuse of the IF may adversely affect scientific progress. We suggest five measures to fight this malady: (i) diversify journal club selections, (ii) do not judge science on the publication venue, (iii) reduce the reliance on journal citation metrics for employment and advancement, (iv) discuss the misuse of the IF in ethics courses, and (v) cite the most appropriate sources. If IF mania is indeed a medical condition, the most appropriate course of action may be disimpaction.
    Preview · Article · Oct 2015 · mBio
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    Fausto Almeida · Julie M Wolf · Arturo Casadevall
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    ABSTRACT: Enzymes play key roles in fungal pathogenesis. Manipulation of enzyme expression or activity can significantly alter the infection process, and enzyme expression profiles can be a hallmark of disease. Hence, enzymes are worthy targets for better understanding pathogenesis and identifying new options for combatting fungal infections. Advances in genomics, proteomics, transcriptomics and mass spectrometry have enabled the identification and characterization of new fungal enzymes. This review focuses on recent development in the virulence-associated enzymes from Cryptococcus neoformans . The enzymatic suite of C. neoformans has evolved for environmental survival but several of these enzymes play a dual role in colonizing the mammalian host. We also discuss new therapeutic and diagnostic strategies that could be based on the underlying enzymology.
    Full-text · Article · Oct 2015 · Eukaryotic Cell
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    Full-text · Article · Sep 2015 · The Journal of Infectious Diseases
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    Arturo Casadevall · Ferric C Fang
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    ABSTRACT: In contrast to many other human endeavors, science pays little attention to its history. Fundamental scientific discoveries are often considered to be timeless and independent of how they were made. Science and the history of science are regarded as independent academic disciplines. Although most scientists are aware of great discoveries in their fields and their association with the names of individual scientists, few know the detailed stories behind the discoveries. Indeed, the history of scientific discovery is sometimes only recorded in informal accounts that may be inaccurate or biased for self-serving reasons. Scientific papers are generally written in a formulaic style that bears no relationship to the actual process of discovery. Here we examine why scientists should care more about the history of science. A better understanding of history can illuminate social influences on the scientific process, allow scientists to learn from previous errors and provide a greater appreciation for the importance of serendipity in scientific discovery. Moreover, history can help to assign credit where it is due and call attention to evolving ethical standards in science. History can make science better.
    Preview · Article · Sep 2015 · Infection and immunity
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    Arturo Casadevall · Ferric C Fang
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    ABSTRACT: Fields are the fundamental sociological units of science. Despite their importance, relatively little has been written about their emergence, composition, structure, and function in the scientific enterprise. This essay considers the nature of fields and their important role in maintaining information and providing normative standards for scientific work. We suggest that fields arise naturally as a consequence of increasing information and scientific specialization. New fields tend to emerge as research communities grow, which may reflect biologically determined optima for the size of human groups. The benefits of fields include the organization of scientists with similar interests into communities that collectively define the next important problems to pursue. In the discipline of microbiology, fields are often organized on the basis of phylogenetic differences between microorganisms being studied. Although fields are essential to the proper functioning of science, their emergence can restrict access by outsiders and sustain dogmas that hinder progress. We suggest mechanisms to improve the functioning of scientific fields and to promote interdisciplinary interaction between fields.
    Preview · Article · Sep 2015 · mBio
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    Lisa Brown · Julie M Wolf · Rafael Prados-Rosales · Arturo Casadevall
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    ABSTRACT: Extracellular vesicles (EVs) are produced by all domains of life. In Gram-negative bacteria, EVs are produced by the pinching off of the outer membrane; however, how EVs escape the thick cell walls of Gram-positive bacteria, mycobacteria and fungi is still unknown. Nonetheless, EVs have been described in a variety of cell-walled organisms, including Staphylococcus aureus, Mycobacterium tuberculosis and Cryptococcus neoformans. These EVs contain varied cargo, including nucleic acids, toxins, lipoproteins and enzymes, and have important roles in microbial physiology and pathogenesis. In this Review, we describe the current status of vesiculogenesis research in thick-walled microorganisms and discuss the cargo and functions associated with EVs in these species.
    Full-text · Article · Sep 2015 · Nature Reviews Microbiology
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    Arturo Casadevall · Thomas Shenk

    Preview · Article · Sep 2015 · mBio
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    Preview · Article · Sep 2015 · mBio
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    ABSTRACT: Cryptococcus neoformans is an opportunistic fungal pathogen that has several well-described virulence determinants. A polysaccharide capsule and the ability to produce melanin are among the most important. Melanization occurs both in vitro, in the presence of catecholamine and indole compounds, and in vivo during the infection. Despite the importance of melanin production for cryptococcal virulence, the component and mechanisms involved in its synthesis have not been fully elucidated. In this work, we describe the role of a G1/S cyclin (Cln1) in the melanization process. Cln1 has evolved specifically with proteins present only in other basidiomycetes. We found that Cln1 is required for the cell wall stability and production of melanin in C. neoformans. Absence of melanization correlated with a defect in the expression of the LAC1 gene. The relation between cell cycle elements and melanization was confirmed by the effect of drugs that cause cell cycle arrest at a specific phase, such as rapamycin. The cln1 mutant was consistently more susceptible to oxidative damage in a medium that induces melanization. Our results strongly suggest a novel and hitherto unrecognized role for C. neoformans Cln1 in the expression of virulence traits.
    Full-text · Article · Aug 2015 · Frontiers in Microbiology
  • Anthony Bowen · Arturo Casadevall
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    ABSTRACT: Society makes substantial investments in biomedical research, searching for ways to better human health. The product of this research is principally information published in scientific journals. Continued investment in science relies on society's confidence in the accuracy, honesty, and utility of research results. A recent focus on productivity has dominated the competitive evaluation of scientists, creating incentives to maximize publication numbers, citation counts, and publications in high-impact journals. Some studies have also suggested a decreasing quality in the published literature. The efficiency of society's investments in biomedical research, in terms of improved health outcomes, has not been studied. We show that biomedical research outcomes over the last five decades, as estimated by both life expectancy and New Molecular Entities approved by the Food and Drug Administration, have remained relatively constant despite rising resource inputs and scientific knowledge. Research investments by the National Institutes of Health over this time correlate with publication and author numbers but not with the numerical development of novel therapeutics. We consider several possibilities for the growing input-outcome disparity including the prior elimination of easier research questions, increasing specialization, overreliance on reductionism, a disproportionate emphasis on scientific outputs, and other negative pressures on the scientific enterprise. Monitoring the efficiency of research investments in producing positive societal outcomes may be a useful mechanism for weighing the efficacy of reforms to the scientific enterprise. Understanding the causes of the increasing input-outcome disparity in biomedical research may improve society's confidence in science and provide support for growing future research investments.
    No preview · Article · Aug 2015 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Many of the most widely consumed edible mushrooms are pigmented and these have been associated with some beneficial health effects. Nevertheless, the majority of the reported compounds associated with these desirable properties are non-pigmented. We have previously reported that melanin pigment from the edible mushroom Auricularia auricula can protect mice against ionizing radiation, although no physicochemical characterization was reported. Consequently, in this study we have characterized commercial A. auricula mushroom preparations for melanin content and carried out structural characterization of isolated insoluble melanin materials using a panel of sophisticated spectroscopic and physical/imaging techniques. Our results show that approximately 10% of the dry mass of A. auricula is melanin and that the pigment has physicochemical properties consistent with those of eumelanins, including hosting a stable free radical population. Electron microscopy studies show that melanin is associated with the mushroom cell wall in a similar manner to melanin from the model fungus C. neoformans. Elemental analysis of melanin indicated C,H and N ratios consistent with DHICA/DHI and DHN eumelanin. Validation of the identity of the isolated product as melanin was achieved by EPR analysis. A. auricula melanin manifested structural differences, relative to the C. neoformans melanin, with regards to the variable proportions of alkyl chains or oxygenated carbons. Given the necessity for new oral and inexpensive radioprotective materials coupled with the commercial availability of A. auricula mushrooms, this product may represent an excellent source of edible melanin.
    Full-text · Article · Aug 2015 · Journal of Agricultural and Food Chemistry
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    Arturo Casadevall
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    ABSTRACT: In 2015, the American Society for Microbiology (ASM) General Meeting essentially achieved gender equity, with 48.5% of the oral presentations being given by women. The mechanisms associated with increased female participation were (i) making the Program Committee aware of gender statistics, (ii) increasing female representation among session convener teams, and (iii) direct instruction to try to avoid all-male sessions. The experience with the ASM General Meeting shows that it is possible to increase the participation of female speakers in a relatively short time and suggests concrete steps that may be taken to achieve this at other meetings. Public speaking is very important for academic advancement in science. Historically women have been underrepresented as speakers in many scientific meetings. This article describes concrete steps that were associated with achieving gender equity at a major meeting. Copyright © 2015 Casadevall.
    Preview · Article · Aug 2015 · mBio

Publication Stats

26k Citations
3,594.36 Total Impact Points

Institutions

  • 2015
    • Johns Hopkins Bloomberg School of Public Health
      • W. Harry Feinstone Department of Molecular Microbiology and Immunology
      Baltimore, Maryland, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2001-2015
    • Yeshiva University
      • • Department of Microbiology & Immunology
      • • Division of Infectious Diseases
      • • Department of Medicine
      • • Division of Allergy and Immunology
      New York, New York, United States
  • 1990-2015
    • Albert Einstein College of Medicine
      • • Department of Microbiology & Immunology
      • • Department of Pediatrics
      • • Infectious Diseases
      • • Department of Medicine
      • • Department of Nuclear Medicine
      • • Department of Cell Biology
      New York, New York, United States
  • 2007-2014
    • Federal University of Rio de Janeiro
      • • Instituto de Biofísica Carlos Chagas Filho (IBCCF)
      • • Institute of Biomedical Sciences
      • • Instituto de Microbiologia Professor Paulo de Góes (IMPPG)
      Rio de Janeiro, Rio de Janeiro, Brazil
    • Trinity University of Asia
      Alfonso XIII, Mimaropa, Philippines
  • 2013
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2012
    • University of Coimbra
      • Faculty of Medicine
      Coímbra, Coimbra, Portugal
    • University of Washington Seattle
      Seattle, Washington, United States
    • AECOM
      Sandy, Utah, United States
  • 2010
    • Stanford University
      Stanford, California, United States
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2008
    • Cornell University
      • Department of Biological and Environmental Engineering
      Ithaca, New York, United States
  • 2006-2007
    • Department of Nuclear Medicine
      Nyitra, Nitriansky, Slovakia
  • 2004
    • All India Institute of Medical Sciences
      • Department of Microbiology
      New Delhi, NCT, India
  • 2000
    • Venezuelan Institute for Scientific Research
      Caracas, Distrito Federal, Venezuela
    • Santa Clara Valley Medical Center
      San José, California, United States
  • 1998-1999
    • Georgia State University
      • Department of Chemistry
      Atlanta, Georgia, United States
    • University of Nevada School of Medicine
      Reno, Nevada, United States
  • 1994-1995
    • Harbor-UCLA Medical Center
      Torrance, California, United States