Host defense mechanisms induce genome instability leading to rapid evolution in an opportunistic fungal pathogen

2021 ◽  
Author(s):  
Amanda Smith ◽  
Levi Morran ◽  
Meleah A. Hickman

The ability to generate genetic variation facilitates rapid adaptation in stressful environments. The opportunistic fungal pathogen Candida albicans frequently undergoes large-scale genomic changes, including aneuploidy and loss-of heterozygosity (LOH), following exposure to host environments. However, the specific host factors inducing C. albicans genome instability remain largely unknown. Here, we leveraged the genetic tractability of nematode hosts to investigate whether innate immune components, including antimicrobial peptides (AMPs) and reactive oxygen species (ROS), induced host-associated C. albicans genome instability. C. albicans associated with immunocompetent hosts carried multiple large-scale genomic changes including LOH, whole chromosome, and segmental aneuploidies. In contrast, C. albicans associated with immunocompromised hosts deficient in AMPs or ROS production had reduced LOH frequencies and fewer, if any, additional genomic changes. To evaluate if extensive host-induced genomic changes had long-term consequences for C. albicans adaptation, we experimentally evolved C. albicans in either immunocompetent or immunocompromised hosts and selected for increased virulence. C. albicans evolved in immunocompetent hosts rapidly increased virulence, but not in immunocompromised hosts. Taken together, this work suggests that host-produced ROS and AMPs induces genotypic plasticity in C. albicans which facilitates rapid evolution.

2021 ◽  
Author(s):  
Amanda C Smith ◽  
Meleah A Hickman

The ability to generate genetic variation facilitates rapid adaptation in stressful environments. The opportunistic fungal pathogen Candida albicans frequently undergoes large-scale genomic changes, including aneuploidy and loss-of heterozygosity (LOH), following exposure to physiological stressors and host environments. However, the specific host factors that induce C. albicans genome instability remains largely unknown. Here, we leveraged genetically-tractable nematode hosts to specifically investigate the innate immune components driving host-associated C. albicans genome instability, which include host production of antimicrobial peptides (AMPs) and reactive oxygen species (ROS). C. albicans associated with wildtype, immunocompetent hosts carried multiple large-scale genomic changes including LOH, whole chromosome, and segmental aneuploidies. In contrast, C. albicans associated with immunocompromised hosts deficient in AMPs or ROS production had reduced LOH frequencies and fewer, if any, additional genomic changes. We also found that C. albicans cap1∆/∆ strains deficient in ROS detoxification, were more susceptible to host-produced ROS genome instability compared to wildtype C. albicans. Further, genomic perturbations resulting from host-produced ROS are mitigated by the addition of antioxidants. Taken together, this work suggests that host-produced ROS and AMPs induces genotypic plasticity in C. albicans which may facilitate rapid adaptation and lead to phenotypic changes.


2021 ◽  
Vol 118 (10) ◽  
pp. e2019865118
Author(s):  
Yilun Yu ◽  
Chi Zhang ◽  
Xing Xu

Reconstructing the history of biodiversity has been hindered by often-separate analyses of stem and crown groups of the clades in question that are not easily understood within the same unified evolutionary framework. Here, we investigate the evolutionary history of birds by analyzing three supertrees that combine published phylogenies of both stem and crown birds. Our analyses reveal three distinct large-scale increases in the diversification rate across bird evolutionary history. The first increase, which began between 160 and 170 Ma and reached its peak between 130 and 135 Ma, corresponds to an accelerated morphological evolutionary rate associated with the locomotory systems among early stem birds. This radiation resulted in morphospace occupation that is larger and different from their close dinosaurian relatives, demonstrating the occurrence of a radiation among early stem birds. The second increase, which started ∼90 Ma and reached its peak between 65 and 55 Ma, is associated with rapid evolution of the cranial skeleton among early crown birds, driven differently from the first radiation. The third increase, which occurred after ∼40 to 45 Ma, has yet to be supported by quantitative morphological data but gains some support from the fossil record. Our analyses indicate that the bird biodiversity evolution was influenced mainly by long-term climatic changes and also by major paleobiological events such as the Cretaceous–Paleogene (K–Pg) extinction.


Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 287 ◽  
Author(s):  
Léa Prochasson ◽  
Pierre Jalinot ◽  
Vincent Mocquet

Before the establishment of an adaptive immune response, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defense mechanisms are debated. Among these mechanisms, we focused on an RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as has been recently demonstrated. NMD is a co-translational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition. HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the fittest clones despite genome instability; however, its direct long-term impact remains to be investigated.


2021 ◽  
Vol 8 (1) ◽  
pp. 4
Author(s):  
Anna B. Frerichs ◽  
Mingwei Huang ◽  
Sébastien C. Ortiz ◽  
Christina M. Hull

Spores are essential for the long-term survival of many diverse organisms, due to their roles in reproduction and stress resistance. In the environmental human fungal pathogen, Cryptococcus, basidiospores are robust cells with the ability to cause disease in animal models of infection. Here we describe methods for producing and purifying Cryptococcus basidiospores in quantities sufficient for large-scale analyses. The production of high numbers of pure spores has facilitated the development of new assays, including quantitative germination assays, and enabled transcriptomic, proteomic, and virulence studies, leading to discoveries of behaviors and properties unique to spores and spore-mediated disease.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 776 ◽  
Author(s):  
Shelby J. Priest ◽  
Vikas Yadav ◽  
Joseph Heitman

Diversity within the fungal kingdom is evident from the wide range of morphologies fungi display as well as the various ecological roles and industrial purposes they serve. Technological advances, particularly in long-read sequencing, coupled with the increasing efficiency and decreasing costs across sequencing platforms have enabled robust characterization of fungal genomes. These sequencing efforts continue to reveal the rampant diversity in fungi at the genome level. Here, we discuss studies that have furthered our understanding of fungal genetic diversity and genomic evolution. These studies revealed the presence of both small-scale and large-scale genomic changes. In fungi, research has recently focused on many small-scale changes, such as how hypermutation and allelic transmission impact genome evolution as well as how and why a few specific genomic regions are more susceptible to rapid evolution than others. High-throughput sequencing of a diverse set of fungal genomes has also illuminated the frequency, mechanisms, and impacts of large-scale changes, which include chromosome structural variation and changes in chromosome number, such as aneuploidy, polyploidy, and the presence of supernumerary chromosomes. The studies discussed herein have provided great insight into how the architecture of the fungal genome varies within species and across the kingdom and how modern fungi may have evolved from the last common fungal ancestor and might also pave the way for understanding how genomic diversity has evolved in all domains of life.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2736
Author(s):  
Justyna Karkowska-Kuleta ◽  
Magdalena Smolarz ◽  
Karolina Seweryn-Ozog ◽  
Dorota Satala ◽  
Marcin Zawrotniak ◽  
...  

One of defense mechanisms of the human immune system to counteract infection by the opportunistic fungal pathogen Candida albicans is the recruitment of neutrophils to the site of invasion, and the subsequent production of neutrophil extracellular traps (NETs) that efficiently capture and kill the invader cells. In the current study, we demonstrate that within these structures composed of chromatin and proteins, the latter play a pivotal role in the entrapment of the fungal pathogen. The proteinous components of NETs, such as the granular enzymes elastase, myeloperoxidase and lactotransferrin, as well as histones and cathelicidin-derived peptide LL-37, are involved in contact with the surface of C. albicans cells. The fungal partners in these interactions are a typical adhesin of the agglutinin-like sequence protein family Als3, and several atypical surface-exposed proteins of cytoplasmic origin, including enolase, triosephosphate isomerase and phosphoglycerate mutase. Importantly, the adhesion of both the elastase itself and the mixture of proteins originating from NETs on the C. albicans cell surface considerably increased the pathogen potency of human epithelial cell destruction compared with fungal cells without human proteins attached. Such an implementation of adsorbed NET-derived proteins by invading C. albicans cells might alter the effectiveness of the fungal pathogen entrapment and affect the further host colonization.


mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Amanda C. Smith ◽  
Meleah A. Hickman

ABSTRACT Candida albicans is an opportunistic fungal pathogen of humans that is typically diploid yet has a highly labile genome tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial for C. albicans to adapt to changing or stressful environments, like those encountered in the host. Genetic variation occurs via stress-induced mutagenesis or can be generated through its parasexual cycle, in which tetraploids arise via diploid mating or stress-induced mitotic defects and undergo nonmeiotic ploidy reduction. However, it remains largely unknown how genetic background contributes to C. albicans genome instability in vitro or in the host environment. Here, we tested how genetic background, ploidy, and the host environment impacts C. albicans genome stability. We found that host association induced both loss-of-heterozygosity events and genome size changes, regardless of genetic background or ploidy. However, the magnitude and types of genome changes varied across C. albicans strain background and ploidy state. We then assessed if host-induced genomic changes resulted in fitness consequences on growth rate and nonlethal virulence phenotypes and found that many host-derived isolates significantly changed relative to their parental strain. Interestingly, diploid host-associated C. albicans predominantly decreased host reproductive fitness, whereas tetraploid host-associated C. albicans increased host reproductive fitness. Together, these results are important for understanding how host-induced genomic changes in C. albicans alter its relationship with the host. IMPORTANCE Candida albicans is an opportunistic fungal pathogen of humans. The ability to generate genetic variation is essential for adaptation and is a strategy that C. albicans and other fungal pathogens use to change their genome size. Stressful environments, including the host, induce C. albicans genome instability. Here, we investigated how C. albicans genetic background and ploidy state impact genome instability, both in vitro and in a host environment. We show that the host environment induces genome instability, but the magnitude depends on C. albicans genetic background. Furthermore, we show that tetraploid C. albicans is highly unstable in host environments and rapidly reduces in genome size. These reductions in genome size often resulted in reduced virulence. In contrast, diploid C. albicans displayed modest host-induced genome size changes, yet these frequently resulted in increased virulence. Such studies are essential for understanding how opportunistic pathogens respond and potentially adapt to the host environment.


1994 ◽  
Vol 144 ◽  
pp. 29-33
Author(s):  
P. Ambrož

AbstractThe large-scale coronal structures observed during the sporadically visible solar eclipses were compared with the numerically extrapolated field-line structures of coronal magnetic field. A characteristic relationship between the observed structures of coronal plasma and the magnetic field line configurations was determined. The long-term evolution of large scale coronal structures inferred from photospheric magnetic observations in the course of 11- and 22-year solar cycles is described.Some known parameters, such as the source surface radius, or coronal rotation rate are discussed and actually interpreted. A relation between the large-scale photospheric magnetic field evolution and the coronal structure rearrangement is demonstrated.


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