Posts Tagged ‘Fungi’
Humans think they’re so smart, giving themselves credit for inventing stuff like the the wheel, fire, and agriculture. Well think again, because we’re not the first to invent farming. Cultivation of crops for nourishment has evolved a few times among eukaryotes. The best known examples include ants, termites, beetles, and, around 10,000 years ago, humans. It turns out that the soil fungus Morchella crassipes acts as a bacterial farmer, involving habitual planting, cultivation and harvesting of bacteria.
It’s fairly obvious what the fungus gets out of this arrangement – it’s in it for all the lovely reduced carbon those tasty bacteria provide. But what about the bacteria – do they get some benefit from the arrangement? It seems that they might. Soil is not the easiest medium for cells to disperse in, and by using the fungal hyphae as a sort of motorway network, this would seem to be more of a mutualistic arrangement, albeit one in which some of the cells wind up as lunch for the farmer.
Pathogens are often described by the nature of their relationship with their hosts. At one extreme are species that are entirely dependent on their host to complete their life cycle (often called obligate parasites). At the other are opportunistic species, which live as saprobes on dead organic matter, but can also invade living organisms (often called facultative pathogens). In between lies an array of combinations ranging in their degree of host dependency and ability to cause disease.
Another way to categorize pathogens is according to their pathogenic lifestyle and disease characteristics. In this case, different terminology is used for plant and animal pathogens: plant-attacking fungi are usually categorized according to the way they feed on the host, e.g., biotrophic or necrotrophic pathogens. Fungi that cause disease in animals are usually described according to the type of disease they cause, e.g., superficial or invasive mycoses. Therefore, we tend to think about fungal pathogens of plants and animals in different terms and treat them separately. Yet fungi attacking animals or plants are actually closely related. Moreover, close examination of animal and plant pathosystems reveals that fungal pathogens in both groups share similar infection strategies and sometimes even cause similar symptoms (although similarity in symptoms doesn’t necessarily indicate similar mechanism). For example, pH-lowering molecules, such as oxalic acid, are virulence factors against plant, animal, and insect hosts. This warrants revisiting the terminology and the way in which we think about fungal pathogens of animals and plants.
And on to:
The yeast Candida albicans is well known as the most common agent of symptomatic fungal disease, but its more typical role is as a permanent resident of the healthy gastrointestinal microbiome. Longitudinal molecular typing studies indicate that disseminated C. albicans infections originate from individuals’ own commensal strains, and the transition to virulence is generally thought to reflect impaired host immunity. Nevertheless, the ability of this commensal pathogen to thrive in radically different host niches speaks to the existence of functional specializations for commensalism and disease. To investigate the C. albicans commensal lifestyle, researchers developed a mouse model of stable gastrointestinal candidiasis in which the animals remain healthy, despite persistent infection with high titers of yeast. Using this model, they found that a C. albicans mutant lacking the Efg1 transcriptional regulator had enhanced commensalism, such that mutant cells strongly outcompeted wild-type cells in mixed infections.
Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism. (2013) Nature Genetics 45, 1088–1091. doi:10.1038/ng.2710
Among ∼5,000,000 fungal species, C. albicans is exceptional in its lifelong association with humans, either within the gastrointestinal microbiome or as an invasive pathogen. Opportunistic infections are generally ascribed to defective host immunity but may require specific microbial programs. Here we report that exposure of C. albicans to the mammalian gut triggers a developmental switch, driven by the Wor1 transcription factor, to a commensal cell type. Wor1 expression was previously observed only in rare genetic backgrounds, where it controls a white-opaque switch in mating. We show that passage of wild-type cells through the mouse gastrointestinal tract triggers WOR1 expression and a novel phenotypic switch. The resulting GUT (gastrointestinally induced transition) cells differ morphologically and functionally from previously defined cell types, including opaque cells, and express a transcriptome that is optimized for the digestive tract. The white-GUT switch illuminates how a microorganism can use distinct genetic programs to transition between commensalism and invasive pathogenesis.
My Leicester colleague Catherine Pashley has done a lot of work in this area, so I was interested in this recent minireview in PLOS Pathogens.
- What Is Asthma?
- Why Do Fungi Make Spores? And a Guide to Terminology
- Do Fungal Spores Cause Asthma?
- Which Species Are Associated with Asthma?
- If Identification to Species Matters, Will New Tools Provide Needed Data?
Asthma and the Diversity of Fungal Spores in Air. (2013) PLoS Pathog 9(6): e1003371. doi:10.1371/journal.ppat.1003371
The diversity of fungal spores in air is vast, but research on asthma focuses on a handful of easily identified, culturable species. Ecologists are developing new tools to probe communities and identify the full complement of fungi in habitats. These tools may enable identification of novel asthma triggers, but scientists involved in public health or medicine rarely interact with mycologists focused on ecology. With this primer, my aim is to facilitate communication by providing doctors with a basic, modern guide to spores, by teaching mycologists the essential facts of asthma, and by providing patients with a succinct summary of what is known about spores and asthma. By highlighting the use of emerging metagenomics technologies in ecology, I intend to illustrate how these tools might be used to more thoroughly understand the potential diversity of fungi involved in asthma.
Pathogenesis of invasive fungal infections. Curr Opin Infect Dis. 27 Feb 2013
Invasive fungal infection (IFI) is increasingly being recognized as a significant cause of morbidity and mortality in immunosuppressed patients. This review focuses on the latest literature reports concerning the pathogenesis of IFI in this population. New virulence factors of Candida and Aspergillus have recently been identified. The past few months have brought significant advances in our understanding of how the immune system acts against fungal infection, especially with regard to the role of mucosa in the innate immune system, the arsenal of innate immune recognition receptors and the pathways connecting innate and adaptive immunity. Knowledge of fungal pathogenesis and host immune response can help to optimize the management of fungal infections. Greater understanding of these processes may aid physicians in developing better prophylactic measures and antifungal or immunomodulatory therapies.
The second article discusses the influence of temperature on invasive fungi – something that is highly significant for organisms such as Cryptococcus neoformans, Histoplasma capsulatum, and Aspergillus fumigatus which normally grow in soil but can make the transition to invade the body:
Surviving the Heat of the Moment: A Fungal Pathogens Perspective. (2013) PLoS Pathog 9(3): e1003163. doi:10.1371/journal.ppat.1003163
Temperature is a critical parameter continually monitored by microorganisms. The dynamic environments inhabited by microorganisms evoke constant and effective environmental response strategies that have been elaborated over evolutionary time. For example, a significant rise or fall in ambient temperature initiates a stress response in the organism, commonly known as heat-shock or cold-shock responses, respectively. The phenomenon of temperature sensing has long been studied in microorganisms such as bacteria, but these mechanisms are only recently being translated to pathogenic fungi.
The ability of pathogenic microorganisms to assimilate nutrients from their host environment is one of the most fundamental aspects of infection. To counteract this, hosts attempt to withhold essential micro-nutrients from potentially harmful microbes to limit, or even prevent, their growth. This process is called nutritional immunity. For example, vertebrates, such as humans, express several iron-binding molecules to maintain extremely low free levels of this metal in the body. To overcome this restriction, successful pathogens have evolved sophisticated mechanisms to assimilate iron. These include high affinity transporters, siderophores, and transferrin-, ferritin-, and haem-binding proteins. Iron acquisition is considered a vital virulence factor for many pathogens. However, nutritional immunity does not begin and end with iron. Vertebrates have also developed mechanisms to sequester other essential metals, such as zinc. The importance of zinc sequestration and the strategies that successful pathogens employ to overcome this has only recently been realized.
Pneumocystis is an unusual fungus that is an opportunistic pathogen, causing an asymptomatic or mild infection in the normal host but pneumonia (PcP) in immunocompromised hosts. Untreated, the mortality rate from PcP approaches 100%. Even with treatment, mortality rates approach 10–20%. It is a ubiquitous organism infecting a wide array of mammalian species. Although the reservoir of infection for Pneumocystis has not been defined, direct airborne transmission from host to host has been proven under experimental conditions in rats.
The study of Pneumocystis has been problematic due to the inability to cultivate the organism or manipulate its cellular or molecular characteristics. As recently as the 1970s, a student studying Pneumocystis would have come away with the following understanding of its basic biology and function as a pathogen: Pneumocystis is an organism of low virulence found in many mammalian species. In humans, Pneumocystis pneumonia is a zoonosis resulting from reactivation of a latent infection acquired early in life. This concept of Pneumocystis arose largely through analogy to existing knowledge about other organisms to explain clinical observations, rather than through direct experimentation on the organism.
Over the past 25 years, we have learned more about Pneumocystis through controlled studies that have corrected some of the misconceptions contained in the “old” concept of Pneumocystis contagion stated above. This article is a brief summary of key research observations that give us a better, yet still incomplete, understanding of how Pneumocystis maintains its existence as an opportunistic pathogen.
Invasive fungal infections are devastating. Despite state-of-the-art antifungal therapy, the mortality rates for invasive infections with the three most common species of human fungal pathogens are Candida albicans, 20%–40%; Aspergillus fumigatus, 50%–90%; and Cryptococcus neoformans, 20%–70%. Although invasive fungal infections can affect people with intact immune systems, the vast majority of disease occurs in the setting of an immunocompromised host.
The dismal outcomes for invasive fungal infections cannot be completely attributed to a lack of efficacious antifungal drugs. However, because most patients with invasive fungal infections are immunocompromised, the immune system cannot effectively assist in the clearance of the infection, and consequently, the success of treatment is more dependent on the efficacy of the antifungal agent than in the setting of an immunocompetent host. Unfortunately, our repertoire of antifungal agents is limited, particularly in comparison to the number of agents available for bacterial infections. In fact, it took 30 years for the newest class of antifungal drugs, the echinocandins, to progress from bench-to-beside. Furthermore, it is sobering to consider that the gold standard therapy for cryptococcal meningitis, a disease that kills more than 650,000 per year world-wide, is based on medications (amphotericin B and flucytosine) that were discovered nearly 50 years ago.
“Here are two indisputable facts: we are living in the age of mammals, and immunologically intact mammals are highly resistant to fungal diseases, such that most human systemic fungal are considered “opportunistic”. Could these two facts be connected? The mammalian lifestyle is characterized by endothermy, homeothermy, and care for the young, including nourishment via lactation, all of which are energetically costly activities. In contrast, reptiles, which are ectotherms, require about one-tenth of the daily mammalian energy needs, and reptilian development is faster and requires less parental involvement. Given this energy handicap, how did mammals replace reptiles as the dominant land animals? This essay further develops the hypothesis originally proposed seven years ago that fungi contributed to the emergence of mammals by creating a fungal filter at the end of the Cretaceous that selected for the mammalian lifestyle and against reptiles.”