Tag Archives: Basidiomycetes

Book Review: Cryptococcus – From Human Pathogen To Model Yeast

I wrote the following book review for the Mycological Society of America‘s Inoculum newsletter and I think the book is a great resource if you study Cryptococcus — so I am reproducing my review here.  You can also find a copy of the review here.

cryptococcus book cover for web

Cryptococcus: From Human Pathogen To Model Yeast. 2010.  Joseph Heitman, Thomas R. Kozel, Kyung J. Kwon-Chung, John R Perfect, and Arturo Casadevall (Eds.).  ASM Press, Washington, DC.

The yeast-forming basidiomycete genus, Cryptococcus, has emerged as a significant model for both fungal genetics and pathogenicity.  A long history of research compounded with numerous laboratory resources, as well as two sequenced genomes, have yielded a great deal of information on this enigmatic fungus.  The new book Cryptococcus: From Human Pathogen To Model Yeast, edited by Heitman, Kozel, Kwon-Chung, Perfect, and Casadevall, features contributions from 123 authors and summarizes a vast amount of data as well as synthesizes disparate concepts on the biology of Cryptococcus.  If you consider Casadevall & Perfect’s 1998 tome Cryptococcus neoformans as the groundwork for this book, then these 646 pages are evidence for the explosive advance of knowledge on Cryptococcus that has accrued over the last 12 years.

Cryptococcus species, arguably the most important fungal pathogen of mammals, are common in immuno-compromised hosts; HIV-associated cryptococcosis alone infects more than 1 million people per year.  For example, Cryptococcus has been laboratory confirmed in Sub-Saharan African countries to be responsible for anywhere from 10 to 70% of fatal meningitis cases over the last two decades.  A well-publicized outbreak of a particularly virulent strain of C. gattii was determined to be the causative agent of more than 200 cases of human meningitis in non-immuno compromised individuals within the Pacific Northwest over the last decade.  A concerted global consortium of medical mycology researchers ­ the majority of whom are authors of chapters in this book ­have provided the foundation for establishing Cryptococcus as the model system for understanding fungal pathogenesis in both a medical and veterinary setting.

Species of Cryptococcus entered my personal radar when they kept turning up in plant-associated environmental samples.  Wanting to get up to speed with natural history, population genetics, and methods for typing Cryptococcal diversity, this book was an obvious entry point for me.  Chapters here are dedicated to identification from environmental niches – such as the description of avian- or plant-associated vectors – as well as population biology to phylogeography, and species complexes to hybridization.

Copiously illustrated throughout, notable figures include those documenting Cryptococcus morphology, cell and molecular biological networks, secondary metabolite chemistry, and gene and genome structure.  Chapters devoted to phylogeography and species complexes have detailed phylogenetic trees and distribution maps.  Additionally, this wouldn’t be a clinical textbook if it didn’t include a series of color and monochrome plates of human and animal infections that remind you why you have – or haven’t – studied medical mycology.

Mycologists aren’t the only ones who will find this resource useful.  Geared toward a wide array of specialists, this book is equally applicable to the interests of clinicians and physicians, microbiologists and immunologists, disease ecologists and epidemiologists, and, to a lesser extent, public health and policy administrators.  The book succeeds in connecting and interpreting basic research science and applying this knowledge in a clinical context.

The book consists of a whopping 44 chapters separated into seven sections.  These sections are devoted to general biology; genetics and genomics; virulence; environmental interactions and population biology; immune host responses; pathogenesis; and diagnosis, treatment, and prevention.  Each of the sections consist of five to eight chapters and each informative chapter stands on its own – concise enough to allow for discrete chunks of reading without overwhelming the reader.  In fact, I would argue that the book’s greatest strength is cohesive breadth blended with factual depth.  My only criticism ­ and this is an extremely minor one ­ is that the book as a whole is slightly overwhelming in scope.  This by no means indicates a lack of vision from the authors or editors, but reflects their desire to take into consideration the complete state of knowledge relating to Cryptococcus and its biology.  As a result, the contributors have not only provided a truly fascinating and utterly comprehensive collection of everything Cryptococcus, but have set the bar high for the best treatise on fungal biology at the genus level.  I would consider this book essential for anyone working directly with Cryptococcus ­ or wanting to get up to speed ­ and for mycologists looking for a framework to fully grasp the biology of an important model fungus.

Searching For Candidate Effector Proteins of Rust Fungi

The understanding of effector proteins has advanced by leaps and bounds in the last few years.  Secreted by microorganisms interacting with plants, these small proteins enter a host cell and modify physiological changes, most notably influencing the suppression or activation of host directed immunity.  Fungal effector proteins have been characterized in the pathogen infection process as well as the suppression of host defenses in mutualistic associations such as mycorrhizae.  There is a recently published book, edited by Francis Martin & Sophien Kamoun, which addresses the current state of knowledge on the biology of microbial effector proteins.

Published on January 6th in the journal PLOS One, the paper “Using Hierarchical Clustering of Secreted Protein Families to Classify and Rank Candidate Effectors of Rust Fungi” authored by Saunders et al., seeks to describe unknown effector proteins by exploring the diversity of secreted proteins of rust fungi.  The Kamoun Lab has been at the forefront of understanding effector biology in the fungi, and this paper is a significant contribution to understanding how rust fungi invoke pathogenicity on their host plants.

Rust fungi are a monophyletic group of pathogens which cause damage on many important economic crop plants.  In this study, the authors investigated two pathogens with sequenced genomes, Puccinia graminis f. sp. tritici, the cause of wheat stem rust, and poplar leaf rust, Melampsora larici-populina.  By developing an analysis pipeline, the authors inspected the secretome of both fungi to search for putative effector proteins and describe their structure and possible mode of infection into a plant.  Few plant defense mechanisms have been identified for rust fungi.  This study was considered a preliminary step to identify candidate rust effectors in the eventual selection of new resistance (R) genes in plant breeding programs and genome sequencing initiatives.

Eight families of putative effector proteins were identified in the secretomes of P. graminis f. sp. tritici and M. larici-populina, and a total of 6663 proteins were identified by the pipeline, with 2826 proteins containing secretion signal peptide regions.  Analysis of the protein motifs identified several conserved cysteine motifs common to other effector proteins previously characterized from fungal and oomycete plant pathogens.  Not surprisingly, the authors identified many previously unrecognized proteins with domains that exhibited similarity to known pathogenicity-related or haustorial-expressed fungal proteins.  Both P. graminis f. sp. tritici and M. larici-populina showed differences in the types of effectors secreted and the numbers of each putative effector tribe.

As I mentioned before, this study should be considered a first step in the identification of pathogenicity related effector proteins from rust fungi.  Next steps would include wet lab characterization and experimental validation for putative effectors identified in this paper.  Additional studies will be needed to address the functional expression of these proteins, as well as the R genes expressed in planta, during the infection process initiated by the rust fungus.  This paper provides an interesting priority list for further studies in this rapidly advancing area of understanding the biology of the intimacies of the plant-fungus interaction.

Old Time Fungal Virulence?

I recently came across an article I found interesting about a widespread geological mystery I was not previously aware of: the presence of filamentous microfossils found worldwide in sediments from the Permian-Triassic boundary transition.  It’s been previously debated that these fossils could be the descendant of either filamentous Ascomycete fungi or freshwater Zygnematateous algae based on their morphology and chemistry.  Either choice represents drastically different scenarios for environmental change that occurred 250 million years on a global scale.  Could the predominance of this organism be the cause of massive plant destruction or the effect of plant destruction from flooding, which is also characteristically found at the end of the Permian period?

In a paper entitled “Fungal virulence at the time of the end-Permian biosphere crisis?”, published in the journal Geology, a group of researchers push the argument toward identifying these fossils – the morphospecies named Reduviasporonites stoschianus – as ancient relatives of the asexually reproducing fungus Rhizoctonia.

Levels of 13C in the fossils do not exclude them from being either fungi or algae, and nitrogen isotope composition would point to a fungal lifestyle.  Cellulosic walls of known filamentous green algae are usually not geologically preserved as well as those identified as Reduviasporonites.  Since there has been no conclusive chemical studies of these microfossils the authors hare rely on microscopic morphological comparisons.

Reduviasporonites stoschianus is found in more than 90% of many geological formations at the time of the Permian–Triassic boundary.  These organisms formed a characteristic “barrel” shaped filaments anywhere between 10 and 90 μm, which look like monilioid hyphae that are typified by Rhizoctonia.  This article states that Rhizoctoniaare mostly Basidiomycota, but some represent Ascomycota” which is incorrect.  Rhizoctonia are placed in the family Ceratobasidiaceae, which is in turn placed in the order Cantharellales of the Basidiomycetes.

It’s certainly difficult to tell the extent of pathogenicity on a host from fossilized material as there few real observations of the invasion of plant tissues.  Furthermore, by observing fossils you are not certain if the presence of these putative fungi is the cause of plant death or a symptom of decline.  While it’s difficult to determine virulence based on fossil evidence, this paper introduces some interesting speculative evidence.