{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js?nzm1e1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js?nzm1e1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;12\\\/14\\\/14\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;12\\\/14\\\/14\u0022}],\u0022ac\u0022:{\u0022spmdc;12\\\/14\\\/14\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;12\\\/14\\\/14\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EPrior to the 20th century, fungal diseases were rare in humans; however, between 1899 and 1999 fungal diseases such as Candida albicans, Coccidiodes immitis, and Aspergillus spp. became distressingly common. The introduction of penicillin in the 1940s changed human flora, and a few years later plastic catheters, which provide microbial access ports, were introduced. Then followed the introduction of intensive care units, organ transplants, and in the late 1980s, the HIV pandemic. All of these together worked to transform \u201cnonpathogens\u201d into \u201cpathogens.\u201d\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EFeatured Meeting - Specialty page\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EFungal Infections\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EPrior to the 20th century, fungal diseases were rare in humans; however, between 1899 and 1999 fungal diseases such as \u003Cem\u003ECandida albicans, Coccidiodes immitis\u003C\/em\u003E, and \u003Cem\u003EAspergillus\u003C\/em\u003E spp. became distressingly common. \u201cWhat happened?\u201d asked Arturo Casadevall, MD, PhD, Albert Einstein College of Medicine, Bronx, New York, USA. His answer was, \u201cWe changed the host.\u201d The introduction of penicillin in the 1940s changed human flora, and a few years later plastic catheters, which provide microbial access ports, were introduced. Then followed the introduction of intensive care units, organ transplants, and in the late 1980s, the HIV pandemic. All of these together worked to transform \u201cnonpathogens\u201d into \u201cpathogens.\u201d\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EPathogenic microbes can be divided into 2 categories, depending on the source of infection: host-acquired (disease results from a disruption of host-microbe relationship) and environment-acquired (disease results from a host with impaired immunity or large inoculum). With the exception of \u003Cem\u003ECandida\u003C\/em\u003E and the dermatophytes, most fungal pathogens are environmentally acquired and are the only known group of pathogens that can drive a species to extinction.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003E\n         \u003Cem\u003ECryptococcus neoformans\u003C\/em\u003E (Cn), a soil fungus that causes life-threatening meningitis in immunocompromised patients and is a facultative intracellular pathogen capable of replication inside macrophages, is of particular research interest to Dr. Casadevall. A unique aspect of Cn\u0027s interaction with macrophages is the phenomenon of nonlytic exocytosis, which involves the escape of fungal cells from the phagocyte with the survival of both cell types [Nicola AM et al. \u003Cem\u003EMBio\u003C\/em\u003E 2011]. Cn is also particularly interesting in that it can also cause disease in plants, insects, and protozoa. Melanin exists on the outside wall of cells to protect against damage from insults such as UV light and heat. Melanized fungal cells have also been shown to demonstrate increased growth relative to nonmelanized cells after exposure to ionizing radiation [Dadachova E et al. \u003Cem\u003EPLoS One\u003C\/em\u003E 2007], raising questions about a potential role for melanin in energy capture and utilization [Zhdanova NN et al. \u003Cem\u003EMycol Res\u003C\/em\u003E 2000]. Research suggests that the virulence of Cn for mammalian cells is a consequence of adaptations that have evolved for protection against environmental predators such as amoebae and provides an explanation for the broad host range of this pathogenic fungus [Steenbergen JN et al. \u003Cem\u003EProc Natl Acad Sci USA\u003C\/em\u003E 2001].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EShifting to an historical perspective, Dr. Casadevall noted that most of Earth\u0027s recent history has been dominated by reptiles. But something shifted 65 million years ago when \u223c70% of all species then living on Earth disappeared within a very short period. What followed was a dramatic increase in mammalian megafauna and a decline in reptilian megafauna.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ERelative to reptiles, mammals require more energy to survive and produce fewer offspring that require considerable care. If reptiles are so fit, why did they not experience a resurgence [Hulbert AJ, Else PL. \u003Cem\u003EAm J Physiol\u003C\/em\u003E 1981]? Dr. Casadevall suggested that a fungal filter selected for mammals over reptiles led to the age of mammals. This theory is supported by data showing that most fungal strains cannot grow at mammalian temperatures (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Robert VA, Casadevall A. \u003Cem\u003EJ Infect Dis\u003C\/em\u003E 2009].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/14\/14\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Temperature Tolerances for Fungi.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1132873376\u0022 data-figure-caption=\u0022Temperature Tolerances for Fungi.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/14\/14\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/14\/14\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/14\/14\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12893\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003ETemperature Tolerances for Fungi.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ERobert A \u0026amp; Casadevall A. Vertebrate Endothermy Restricts Most Fungi as Potential Pathogens. \u003Cem\u003EJ Infect Dis\u003C\/em\u003E. (2009) 200 (10): 1623\u20131626 with permission from Oxford University Press.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EMammalian endothermy enhances fitness by creating exclusionary thermal zones that protect against fungal diseases. When the tradeoff involved between the cost of the excess metabolic rates required to maintain body temperature and the benefit gained by creating a thermal exclusion zone that protects against environmental microbes such as fungi is analyzed, the resulting temperature is 36.7\u00b0C. A temperature that, in Dr. Casadevall\u0027s opinion, is so close to the mammalian temperatures that it is unlikely to be arrived at by coincidence or accident [Bergman A, Casadevall A. \u003Cem\u003EMBio\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EBats provide an example of the relationship between temperature and fungal infection. They have a normal body temperature of 37\u00b0C, but when they hibernate, their temperature drops to 10\u00b0C to 12\u00b0C. It is during this period that they become susceptible to white-nose syndrome (caused by \u003Cem\u003EGeomyces\u003C\/em\u003E spp.), which wakes them in the winter and causes them to die. The issue can be resolved in the laboratory by awakening the hibernating bats and feeding them, thereby increasing their body temperature.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EAdditional support for the temperature theory comes from fossil evidence dating after the meteor impact in the Yucatan Peninsula. This evidence indicates that the resulting fires led to large amounts of smoke and dust, which obscured the Sun and resulted in a shutdown of photosynthesis for \u223c6 months. Global temperatures dropped, vegetation died off, and there was massive proliferation of fungi. One hypothesis is that it was the increase in fungal disease to which reptiles are much more susceptible than mammals that caused so many of them to die off [Casadevall A. \u003Cem\u003EPLoS Pathog\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EMost fungal diseases are from the area around the equator and areas around the planet that are warmer that have allowed the fungi to adapt themselves to warmer temperatures. What has protected humans from fungal diseases has been the distance between the human temperature and the ambient temperature. Dr. Casadevall asked if this means that \u201cas the ambient temperature rises we will see more fungal diseases\u201d? Nonthermal tolerant fungi with pathogenic potential can adapt to higher temperatures. In 1 study that used a newly developed automated continuous culture that takes advantage of a natural selection-adaptation strategy, 2 thermotolerant variants of \u003Cem\u003EMetarhizium anisopliae\u003C\/em\u003E displayed robust growth at 36.5\u00b0C. Thermotolerant variants were entomopathogenic, albeit with complex alterations in virulence parameters such as lethal dose responses and median survival times. Thus raising the possibility that fungus will adapt to survive at higher temperatures as the world becomes warmer [de Crecy E et al. \u003Cem\u003EBMC Biotechnol\u003C\/em\u003E 2009].\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EDr. Casadevall predicted that as the 21st century progresses, fungal disease will increase, new fungal pathogens will emerge, and new pathogenic genera will emerge\u2014some of which will be resistant to current drugs. As a result, some mammals may be in trouble.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/14\/14.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzm1e1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm1e1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}