Trends in Microbiology
ReviewFungal Pathogens: Shape-Shifting Invaders
Section snippets
Fungal Pathogens Alter Cell Shape as Part of Their Virulence Strategy
Most fungi play beneficial roles in the environment but a small subset can cause lethal infections in humans [1]. These pathogenic species grow in a wide range of different morphologies that provide distinct advantages for virulence [2., 3., 4.] (Figure 1, Key Figure). Many fungal pathogens grow as yeast (see Glossary) which are about the size of a red blood cell and are therefore well suited for bloodstream dissemination. By contrast, molds (multicellular chains of filamentous hyphal cells)
Cryptococcus: Yeasts That Cloak Themselves in a Protective Capsule and Shift into Giant Cells
Cryptococcus neoformans is one of the best studied fungi because it is a major cause of lethal fungal infections worldwide due to its ability to infect AIDS patients. The related species Cryptococcus gattii has also gained attention recently for causing clusters of infections in seemingly healthy individuals [1,4,7]. Cryptococcus species grow by budding (Figure 2A) and by forming filamentous cells in nature, but they shift primarily into the budding mode of replication in the host [8]. To get
Histoplasma capsulatum: A Dimorphic Fungal Pathogen That Grows as Hyphal Filaments in the Environment and Shifts to Yeast in the Host
In spite of its species name, Histoplasma capsulatum does not form a capsule. It is part of a group known as thermally dimorphic fungi because it forms filamentous hyphae at low temperatures in the environment but shifts to yeast growth at the elevated temperature of the human body [24,25]. Infection is often initiated when hyphal filaments transition to forming structures known as conidiophores that release small asexual conidia (spores) that are subsequently inhaled into the lung [26]. Thus,
Aspergillus fumigatus: Inhaled Conidia Transform into Invasive Hyphae That Further Shift into an Interconnected Mycelial Network
Filamentous hyphal growth has several virulence advantages, including the ability to invade tissues; the large size of hyphae also prevents phagocytosis. Aspergillus fumigatus, the primary focus of this section, is one of the most common lethal fungal pathogens [31]. It has been a particularly severe problem in immunocompromised individuals, such as bone marrow transplant patients [1]. For comparison, we also describe Rhizopus oryzae, which differs from A. fumigatus in that it forms
Multimorphic Candida Species Form Cell Aggregates and Biofilms
Candida species are distinct from most other fungal pathogens in that they are commensal organisms that colonize the skin or gastrointestinal (GI) tract. Thus, rather than inhaling conidia, patients are usually infected by endogenous organisms that, under conditions such as immune deficiency or biofilm formation, are able to overwhelm host defenses and disseminate. Candida species are also distinct in that most are multimorphic in the host where they transition between budding and filamentous
Coccidioides Species Form Giant Spherules in the Host Containing Hundreds of Endospores
Coccidioides immitis and Coccidioides posadasii are found in the soil in arid regions of the southwestern USA and northwestern Mexico [60]. Although Coccidioides spp. are thermally dimorphic fungi, evolutionarily related to Histoplasma, they undergo very distinct morphological shifts. In soil, they grow as hyphal filaments and then alternating cells in the hyphae transform into arthrospores, which persist in the soil (Figure 5A). When the soil is disturbed, aerosolized arthrospores infect
Concluding Remarks
This review covers a sampling of the major human pathogens, but there is still much to be learned about shape-shifting fungi (see Outstanding Questions). We have only a limited view of fungal morphology in the host from histology. However, fungal strains that produce fluorescent proteins are making it possible to identify new morphological shape transitions in different host niches and after stress conditions such as hypoxia and antifungal therapy [73]. There are also many more fungi with
Acknowledgments
This work was supported by Public Health Service grants from the National Institutes of Health awarded to J.B.K. (R01GM116048 and R01AI047837) and A.M.N. (R01GM072540). We thank the members of our laboratories for their helpful comments on the manuscript.
Glossary
- Ascus
- a cell structure, containing sexual spores, produced following meiosis by ascomycete fungi.
- Capsule
- a protective layer, composed of polysaccharide chains, that surrounds the cell wall.
- Conidia
- asexual spores produced by molds; they are also called conidiospores.
- Cyst
- a term used to describe an ascus that contains the spores (ascospores) that form after mating of Pneumocystis jirovecii. This term is a holdover from when P. jirovecii was thought to be a parasite. (DNA sequencing revealed that it
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