Exserohilum rostratum, the killing fungus

24 October 2012 by Danny Haelewaters, posted in Fungi

There are hundreds of topics I could write about. The hardest part about writing is choosing a suitable topic and sticking with it until the end. This time, however, it was a little easier than normally due to the interesting nature of Exserohilum rostratum. Ever heard of it? It’s a fungus that seems to cause fatal meningitis, right now. Wait, right now?! Let’s find out what is going on.

It’s been a while since Charles Frank Drechsler (1923) described the ascomycete fungus Helminthosporium rostratum [1]. Then Stanley J. Hughes (1958) excluded from the genus Helminthosporium a group of graminicolous species corresponding to another genus, Ito's Drechslera (1930). Robert A. Shoemaker (1959) described even a third genus Bipolaris to exclude species that were not like Drechslera from Helminthosporium. These genera have been rejected by different authors for various reasons and likewise, they have been accepted for various other reasons. Anyway, to make a long story short: the current accepted name for what we are talking about right now is Exserohilum rostratum.

It is interesting to consider that this fungus belongs to the Ascomycota. Members of this phylum go through asexual (anamorphic) phases during which they reproduce rapidly by mitospores or conidia (generated through the cellular process of mitosis). The sexual phase with the asci is called the teleomorph.

General life cycle of ascomycetes, with both the sexual and asexual phase

Back to Exserohilum rostratum, is this the anamorph or teleomorph? Let’s have a look at the original description of Helminthosporium rostratum [1].

Occurring on the dry leaves of Eragrostis major, Host.

Conidiophores dark olivaceous, emerging singly or in groups of 2 to 5 from stomata or between epidermial cells, the swollen bases more or less united; measuring 6 to 8 by 40 to 180 µ; 1 to 6 septate, the septa separated by intervals of 15 to 40 µ; proliferating the first spore 40 to 140 µ from the base, and successive spores at intervals of 10 to 30 µ, at the apices of well-defined geniculations.

Conidia, when mature, dark olivaceous; straight or less frequently somewhat curved; often short, widest at or somewhat below the middle, tapering moderately or more markedly towards both ends, the hemispherical apex abruptly rounded off, the basal end somewhat more acute, often exhibiting a rounded conical contour; or less frequently produced at the tip into a more or less elongated rostrate prolongation.

There it is: Exserohilum rostratum (= Helminthosporium rostratum) is the asexual state, the anamorph, since its description is almost purely based on conidial characteristics.

An anaomorph/teleomorph connection for this fungus was only made in 1976, when Setosphaeria rostrata K.J. Leonard was described and recognized as teleomorph of Exserohilum rostratum.

Biocontrol agent

Human impact on the natural environment has expanded tremendously over the past century. Rapid population growth and a globalized economy have caused widespread pollution, habitat destruction and climate change. One major but often little appreciated problem in our increasingly interconnected global biosphere is the ecological disturbance caused by animals and plants invading new ecosystems. Often these invasions occur unintentionally, for example through ships releasing their ballast water into foreign waters, or through worldwide trade in agricultural and horticultural products. Many other invasions result from deliberate introductions, which have run out of control.

Invading species disrupt the normal functioning of ecosystems by directly outcompeting native species, destabilizing food webs or affecting the cycling of nutrients through the ecosystem. Invasive species may drive native species to extinction through simple food competition, by using available food resources more efficiently, or by mating with native species to which they are closely related (hybridization). Invasive ‘alien’ species are now considered one of the top drivers for global biodiversity loss.

Red sprangletop, Leptochloa chinensi (Linnaeus) Nees, is a grassy weed originated in tropical Asia. It is distributed throughout Southeast Asia, from East Asia to South Africa, Burma, Sri Lanka, India, Australia, and Japan, where it is an ‘alien’ species. The weed has adapted to moist, swampy places in open habitats and is a huge seed producer (more than 40,000 seeds per plant). Therefore, it is a significant problem in rice, corn, sorghum, and soybean fields. This weed is a serious strain on rice yield. Annual worldwide rice yield loss caused by this weed is estimated to be between 15 - 21%. Now, our fungus of interest Exserohilum rostratum has recently been demonstrated to work as a biocontrol agent against red sprangletop through a two-phase system [2]:

In the first phase, quantitatively sufficient mycelia were cultured in submerged liquid culture. The basal medium contained 20 g of glucose, 2 g of NaNO3, 1 g of K2HPO4, 1g of KH2PO4, 0.5g of MgSO4, 0.2g of CaCl2, 3.4g of polypeptone, 3.4g of yeast extract, 10g of rice oil, and 20g of polyurethane foam (5mm-cubes, Bridgestone Co. Ltd. Tokyo), which provide approximately 3,500 cubes per 1 L of distilled water. The initial pH was adjusted to 5.5 by 0.1 N HCl. Each 500mL-flask containing 150mL of the medium containing polyurethane foam was inoculated with 0.1% (v/v) conidia suspension obtained by plate culture. Following autoclaving, these flasks were incubated on a rotary shaker at 100rpm in the dark.

In the second phase, conidia were produced in the open air. After submerged in liquid culture, the sponge matrix covered with mycelia was separated from the culture broth through filtration using a sieve. To cause the conidiation of the fungus, mycelia on the surface of polyurethane foam were exposed to the air in a beaker at 25° C in a moist chamber.

The authors of this particular research even state that this “two-phase system […] may serve as a promising tool for mass-production of bioherbicides.”

However, there are two sides to every coin

On October 14, 2012 Federal officials reported contaminated injections had sickened 214 people in fifteen states. So far (October 25), 304 people have been diagnosed with meningitis, 23 of whom died, after having had steroid injections into the epidural space as a treatment for back pain. The injections were found to be contaminated with Exserohilum rostratum. This fungus thus seems to have some characteristics that we should take into account when considering using it as a biocontrol agent.

Exserohilum includes several saprobic species in the bark, leaves, and stems of both woody and herbaceous plants, but there’s also a large number of parasitic species. Those affecting graminaceous hosts are pretty well known, because of their possible use as effective biocontrol. Next to these economically important forms, many other species of Exserohilum are recorded as thriving on various members of the grass family, but have remained more or less obscure because either the hosts affected were of little economic value, or their parasitism caused little or no observable damage. I think ‘obscure’ is the correct word when thinking back to the 23 people who have died because of the injection of Exserohilum spores into the epidural space.

Although ubiquitous, members of the genus Exserohilum are rarely pathogenic for humans. Only three species have been shown to parasitize humans: E. rostratum, E. longirostratum and E. macginnisii [3]. The most common type of infections are sinusitis and skin infections, although also a few cases of cerebral abscesses, keratitis, osteomyelitis, prosthetic valve endocarditis and disseminated infection have been described.

In 2007 a child undergoing treatment for acute lymphoblastic leukemia (ALL) was infected by Exserohilum rostratum, causing cutaneous phaeohyphomycosis. The infection was due to contaminated intravenous dressings. In total, only ten cases of primary cutaneous skin infections due to Exserohilum have been described in the English literature. The problems with these reports are the incomplete data on follow-up and the lack of discussion of the potential use of newer antifungal agents. However, treatment of these cutaneous infections is primarily based on aggressive surgical removal combined with antifungal therapy.

The Centre Hospitalier Universitaire Saint-Justine (Montreal, Quebec) decided after the 2007 Exserohilum rostratum case to replace all wooden boards used to secure intravenous lines by Plexiglas covered with sterile gauze. The replacement occurred as part of an infection control policy and is said to be potentially lifesaving [3]. However, no fungal traces were found, although certain tapes and wooden devices have been reported to be linked with fungal infection.

Last month, 17 states reported cases with fungal meningitis. The outbreak was traced back to Exserohilum rostratum contaminated medication for epidural steroid injections, packaged and marketed by the New England Compounding Center (Framingham, MA). It is estimated that more than 14,000 people may have been exposed to the contaminated medication – they are not necessarily infected.

 

As a conclusion we may want to limit working with Exserohilum rostratum. If this invasive Leptochloa weed is still bothering you, I suggest trying to raise a green manuring legume in the summer in crop fields that would be ploughed in situ at the time of preparing fields [4]. I’m sure this won’t kill you.

References:

[1] Drechsler CF 1923, Journal of Agricultural Research 24: 641-740. [2] Yamaguchi K, Nagai K & E Matsumoto 2009. Bulletin of Minamikyushu University 39A: 73-77. [3] Saint-Jean M, St-Germain G, Lafarrière C & B Tapiero 2007. Canadian Journal of Infectious Diseases and Medical Microbiology 18: 200-202. [4] Kathiresan KR 2006. NIAES Symposium, Japan. [5] Leonard KJ 1976, Mycologia 68: 402-411.

I thank Sarah Verhaeghen, Rachel Engstrand and Donald H. Pfister for giving me valuable comments.

Exserohilum rostratum conidia. © Centers for Disease Control and Prevention (CDC)

And last but not least, for the fans, I've got some pretty awesome taxonomy [5], just because I (and not only me, so it seems) like to explore the history of names:

Exserohilum rostratum (Drechsler) K.J. Leonard & Suggs, 1974, Mycologia 66: 290.

Helminthosporium rostratum Drechsler, 1923, J. Agric. Res. 24: 724.

Bipolaris rostrata (Drechsler) Shoemaker, 1959, Canad. J. Bot. 37: 883.

Drechslera rostrata (Drechsler) Richardson & Fraser, 1968, Trans. Brit. Mycol. Soc. 51: 148.

Exserohilum halodes (Drechsler) K.J. Leonard & Suggs, 1974, Mycologia 66: 290.

Helminthosporium halodes Drechsler, 1923, J. Agric. Res. 24: 709.

Bipolaris halodes (Drechsl.) Shoemaker, 1959, Canada. J. Bot. 37: 883.

Drechslera halodes (Drechsl.) Subramanian & Jain, 1966, Current Sci. 35: 354.

Helminthosporium halodes Drechsler var. tritici Mitra, 1931, Trans. Brit. Mycol. Soc. 15: 287.

Helminthosporium halodes Drechsler var. elaeicola Kovachich, 1954, Trans. Brit. Mycol. Soc. 37: 423.


12 Responses to “Exserohilum rostratum, the killing fungus”

  1. Khalil A. Cassimally Reply | Permalink

    Wow, some scary stuff there! I've also read that of the estimated 14,000 people exposed to the fungus, there's a number of them will develop meningitis at some point. Can't believe what those people who took the steroids are going through right now.

    On a brighter note, love that taxonomy aside you've included! Looking forward to more posts from you and welcome to SciLogs.com!

  2. Tom Hennessy Reply | Permalink

    I have read E. rostratum is used to increase production of drugs? Was it used to increase production in this case?

  3. Mary Ellen Lewis Reply | Permalink

    This is a 'scapegoating' issue ... Can any trace backwards find documentation of this particular fungus causing meningitus?

    • Danny Haelewaters Reply | Permalink

      You should definitely read this paper: Saint-Jean M, St-Germain G, Lafarrière C & B Tapiero 2007. Hospital-acquired phaeohyphomycosis due to Exserohilum rostratum in a child with leukemia. Canadian Journal of Infectious Diseases and Medical Microbiology 18: 200-202. It is not just scapegoating!

  4. Tom Hennessy Reply | Permalink

    "Hospital-acquired phaeohyphomycosis due to Exserohilum rostratum in a child with leukemia."
    This could be argued to be due to the increased iron levels commonly found in leukemia patients. A researcher recently expired due to the fact the plague vaccine he was working on became activated in his body because unbeknownst to him he had hemochromatosis , iron excess which allowed the plague to access this high iron and kill him. Fungus is the same. Ciclopirox, an antifungal being repositioned for cancer, is an iron chelator.

    Could the leukemia patient and these patients who do manifest meningitis may only be manifesting BECAUSE of the increased iron in their bodies, JUST like the researcher who died?
    "iron overload characteristic of hemochromatosis may have allowed the KIM D27 strain to overcome the pgm deletion and acquire enough iron to become dangerous"

  5. Jack Ingram Reply | Permalink

    Exactly. The point to be made is that, given rarity, was it intentional. Did somebody get revenge? Easy to acquire and grow, still rare as a common infection from the medication itself. I don't buy it.

    Page 990, Diagnostic Micro, Saunders & Elsevier, 3rd ed.:
    The known fungal meningitis causes from immunosuppressive drugs as a secondary infection are:
    - Aspergillus
    - Zygomycetes (Mucor, Rhizopus, Absidia)
    - Candida ssp.
    - Blastomyces dermatitidis
    - Cryptococcus neoformans (found in HIV patients)
    - Coccidiodes ssp.
    - and Pseudallescheria boydii

    As if someone wanted to cover it up as a secondary infection, but no other listed fungus is as easily acquired, grown, transported, and safely deployed. A dirty lawn crew would have to run through the lab.

    Good luck to mycologists and microbiologists studying this.

  6. Jack Ingram Reply | Permalink

    Tom Hennessy asked about drug production. Here is a topic that would validate the lab mismanagement story without getting into too much conspiracy:

    http://en.wikipedia.org/wiki/Corticosteroid

    In 1952, D.H. Peterson and H.C. Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.

    Peterson D.H., Murray, H.C. (1952). "Microbiological Oxygenation of Steroids at Carbon 11". J. Am. Chem. Soc. 74 (7): 1871–2. doi:10.1021/ja01127a531

    Could Exserohilum act like Rhizopus mold? Was this a new production patent getting out of hand, or is the government purposefully misdirecting the media outlets?

    Opinion: 1)There is a corporate protectionist law that allows drugs to be put on the shelf without 3rd party safety and efficacy research. This is why the FDA throws their hands up. To reverse that law might imply new patent infringement via corporate espionage. All of this gets in the way of patient/customer safety. It is the primary reason why the FDA is rendered useless. Our government is run by corporate lawyers and lobby houses, not leaders looking out for your safety.
    2) After doing some basic research on Avian and Swine Flu, discovered the CDC's primary job is to obstruct information gathering for "National Security" reasons. If you go looking for some real stats, the website directs you to a retarded spreadsheet for journalists to decipher, or the WHO website which will post stats from a handful of SE Asia and Middle East countries. The question I asked was on current cases here in the U.S. Do you want people to run and spread the disease or do you want them to stay in their houses and die or go to the hospital? The reason why the CDC website is intellectually devoid is for population control during an outbreak or epidemic. A waste of taxpayer dollars. Anybody studying microbiology will tell you to not waste time with gov't filtered information. Even the CDC's Vacationers Report is probably not very real.

    Read that Peterson/Murray essay.

  7. Ghada Reply | Permalink

    Hi, I was wondering about the life cycle of Ascomycete diagram. I am a student and I want to reference it in my presentation. Can you please tell me the reference?

    Thanks!

  8. Deb Samson Reply | Permalink

    May I ask a question … I am one of the 14,000 who were injected with the epidural fungus! I have NOT acquired meningitis, although have been under vigilant watch for the first three-month period, which ended 12/12/12. I know you may not be able to recommend but I am very curious to see if there is any herbal stuff out there to come against the fungus? My symptom now is that of very low immunity and being very tired … I would love to see if there is something in natural form that will attack this fungus and also to increase my immunity. This question may not relate to your studies at all, but it can't hurt to ask. Thanks so much!

  9. Jack Simmons Reply | Permalink

    I suggest one avoids injecting any contaminated materials into the meninges, which was the real cause of this disaster. The compounding lab violated the rules designed to keep injections sterile, rules that work fine when followed.

    We don't get worked up in a tizzy when there is a fatal automobile crash when someone breaks the rules on drunk driving. Why all this fear and agony over common, everyday molds?

    Exserohilum rostratum is found growing on grasses. There is a good chance this benign mold was growing on your lawn last summer. My hypothesis is someone brought the spores of E. rostratum with them after mowing the lawn. They did not follow the rules for preventing contamination in compounding pharmacies - setting up this tragedy.

    By the way, the index case for this matter was caused by Aspergillus fumigatus, another common mold we all are in contact with almost every day of our life. Again, don't inject mold spores, bacteria, viruses, or any other pathogens into your meninges.

  10. Cornell Reply | Permalink

    Hello,
    I am a medical researcher at Cornell and the diagram you used in your article has caught my attention. We are extensively researching the organism in the hopes of aiding those affected. It would be of great help if you could tell me where you found the life cycle diagram. Thank you for your assistance and I look forward to hearing from you.

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