The Persistent Challenge of Pneumocystis Growth Outside the Mammalian Lung: Past and Future Approaches

The pathogenic fungi in the genus, Pneumocystis, have eluded attempts to continuously grow them in an ex vivo cultivation system. New data from transcriptomic and genomic sequencing studies have identified a myriad of absent metabolic pathways, helping to define their host obligate nature. These nutrients, factors, and co-factors are acquired from their mammalian host and provide clues to further supplementation of existing media formulations. Likewise, a new appreciation of the pivotal role for the sexual cycle in the survival and dissemination of the infection suggests that Pneumocystis species are obligated to undergo mating and sexual reproduction in their life cycle with a questionable role for an asexual cycle. The lack of ascus formation in any previous cultivation attempts may explain the failure to identify a sustainable system. Many characteristics of these ascomycetes suggest a biotrophic existence within the lungs of the mammalian hosts. In the present review, previous attempts at growing these fungi ex vivo are summarized. The significance of their life cycle is considered, and a list of potential supplements based on the genomic and transcriptomic studies is presented. State of the art technologies such as metabolomics, organoids, lung-on-a chip, and air lift cultures are discussed as potential growth systems.

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Metabolic reprogramming during the Trypanosoma brucei life cycle

F1000Research ◽

10.12688/f1000research.10342.2 ◽

2017 ◽

Vol 6 ◽

pp. 683 ◽

Cited By ~ 31

Author(s):

Terry K. Smith ◽

Frédéric Bringaud ◽

Derek P. Nolan ◽

Luisa M. Figueiredo

Keyword(s):

Life Cycle ◽

Trypanosoma Brucei ◽

Model Organism ◽

Protozoan Parasite ◽

Tsetse Fly ◽

Metabolic Reprogramming ◽

Mammalian Host ◽

Insect Vector ◽

Environmental Signals ◽

Cellular Metabolic Activity

Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites. This review highlights some of these metabolic changes in this early divergent eukaryotic model organism.

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The novel Dbl homology/BAR domain protein, MsgA, of Talaromyces marneffei regulates yeast morphogenesis during growth inside host cells

Scientific Reports ◽

10.1038/s41598-020-79593-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Harshini Weerasinghe ◽

Hayley E. Bugeja ◽

Alex Andrianopoulos

Keyword(s):

Pathogenic Fungi ◽

Host Cells ◽

Microbial Pathogens ◽

Mammalian Host ◽

Host Immune System ◽

Nucleotide Exchange ◽

Phagocytic Cells ◽

Macrophage Infection ◽

Bar Domain ◽

Talaromyces Marneffei

AbstractMicrobial pathogens have evolved many strategies to evade recognition by the host immune system, including the use of phagocytic cells as a niche within which to proliferate. Dimorphic pathogenic fungi employ an induced morphogenetic transition, switching from multicellular hyphae to unicellular yeast that are more compatible with intracellular growth. A switch to mammalian host body temperature (37 °C) is a key trigger for the dimorphic switch. This study describes a novel gene, msgA, from the dimorphic fungal pathogen Talaromyces marneffei that controls cell morphology in response to host cues rather than temperature. The msgA gene is upregulated during murine macrophage infection, and deletion results in aberrant yeast morphology solely during growth inside macrophages. MsgA contains a Dbl homology domain, and a Bin, Amphiphysin, Rvs (BAR) domain instead of a Plekstrin homology domain typically associated with guanine nucleotide exchange factors (GEFs). The BAR domain is crucial in maintaining yeast morphology and cellular localisation during infection. The data suggests that MsgA does not act as a canonical GEF during macrophage infection and identifies a temperature independent pathway in T. marneffei that controls intracellular yeast morphogenesis.

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Cysteine-Rich Hydrophobin Gene Family: Genome Wide Analysis, Phylogeny and Transcript Profiling in Cordyceps militaris

International Journal of Molecular Sciences ◽

10.3390/ijms22020643 ◽

2021 ◽

Vol 22 (2) ◽

pp. 643

Author(s):

Xiao Li ◽

Fen Wang ◽

Yanyan Xu ◽

Guijun Liu ◽

Caihong Dong

Keyword(s):

Life Cycle ◽

Pathogenic Fungi ◽

Class Ii ◽

Cordyceps Militaris ◽

Transcript Profiling ◽

Saprotrophic Fungi ◽

Genome Wide Analysis ◽

Genome Wide ◽

Encoding Genes

Hydrophobins are a family of small secreted proteins found exclusively in fungi, and they play various roles in the life cycle. In the present study, genome wide analysis and transcript profiling of the hydrophobin family in Cordyceps militaris, a well-known edible and medicinal mushroom, were studied. The distribution of hydrophobins in ascomycetes with different lifestyles showed that pathogenic fungi had significantly more hydrophobins than saprotrophic fungi, and class II members accounted for the majority. Phylogenetic analysis of hydrophobin proteins from the species of Cordyceps s.l. indicated that there was more variability among the class II members than class I. Only a few hydrophobin-encoding genes evolved by duplication in Cordyceps s.l., which was inconsistent with the important role of gene duplication in basidiomycetes. Different transcript patterns of four hydrophobin-encoding genes during the life cycle indicated the possible different functions for each. The transcripts of Cmhyd2, 3 and 4 can respond to light and were related with the photoreceptors. CmQHYD, with four hydrophobin II domains, was first found in C. militaris, and multi-domain hydrophobins were only distributed in the species of Cordycipitaceae and Clavicipitaceae. These results could be helpful for further function research of hydrophobins and could provide valuable information for the evolution of hydrophobins.

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Borrelia burgdorferi Lacking BBK32, a Fibronectin-Binding Protein, Retains Full Pathogenicity

Infection and Immunity ◽

10.1128/iai.02035-05 ◽

2006 ◽

Vol 74 (6) ◽

pp. 3305-3313 ◽

Cited By ~ 68

Author(s):

Xin Li ◽

Xianzhong Liu ◽

Deborah S. Beck ◽

Fred S. Kantor ◽

Erol Fikrig

Keyword(s):

Life Cycle ◽

Borrelia Burgdorferi ◽

Deletion Mutant ◽

Binding Protein ◽

Kanamycin Resistance ◽

Binding Activity ◽

Mammalian Host ◽

Wild Type ◽

Fibronectin Binding Protein ◽

Fibronectin Binding

ABSTRACT BBK32, a fibronectin-binding protein of Borrelia burgdorferi, is one of many surface lipoproteins that are differentially expressed by the Lyme disease spirochete at various stages of its life cycle. The level of BBK32 expression in B. burgdorferi is highest during infection of the mammalian host and lowest in flat ticks. This temporal expression profile, along with its fibronectin-binding activity, strongly suggests that BBK32 may play an important role in Lyme pathogenesis in the host. To test this hypothesis, we constructed an isogenic BBK32 deletion mutant from wild-type B. burgdorferi B31 by replacing the BBK32 gene with a kanamycin resistance cassette through homologous recombination. We examined both the wild-type strain and the BBK32 deletion mutant extensively in the experimental mouse-tick model of the Borrelia life cycle. Our data indicated that B. burgdorferi lacking BBK32 retained full pathogenicity in mice, regardless of whether mice were infected artificially by syringe inoculation or naturally by tick bite. The loss of BBK32 expression in the mutant had no adverse effect on spirochete acquisition (mouse-to-tick) and transmission (tick-to-mouse) processes. These results suggest that additional B. burgdorferi proteins can complement the function of BBK32, fibronectin binding or otherwise, during the natural spirochete life cycle.

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DWPF Glass Air-Lift Pump Life Cycle Testing and Plant Implementation

10.2172/824423 ◽

2004 ◽

Author(s):

MICHAEL SMITH

Keyword(s):

Life Cycle ◽

Air Lift

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Metamorphoses of malaria: the role of autophagy in parasite differentiation

Essays in Biochemistry ◽

10.1042/bse0510127 ◽

2011 ◽

Vol 51 ◽

pp. 127-136 ◽

Cited By ~ 15

Author(s):

Isabelle Coppens

Keyword(s):

Life Cycle ◽

Complex Life Cycle ◽

Mammalian Host ◽

Protozoan Parasites ◽

Membrane Complex ◽

Autophagic Process ◽

Inner Membrane Complex ◽

Form Development ◽

High Degree

Several protozoan parasites undergo a complex life cycle that alternates between an invertebrate vector and a vertebrate host. Adaptations to these different environments by the parasites are achieved by drastic changes in their morphology and metabolism. The malaria parasites must be transmitted to a mammal from a mosquito as part of their life cycle. Upon entering the mammalian host, extracellular malaria sporozoites reach the liver and invade hepatocytes, wherein they meet the challenge of becoming replication-competent schizonts. During the process of conversion, the sporozoite selectively discards organelles that are unnecessary for the parasite growth in liver cells. Among the organelles that are cleared from the sporozoite are the micronemes, abundant secretory vesicles that facilitate the adhesion of the parasite to hepatocytes. Organelles specialized in sporozoite motility and structure, such as the inner membrane complex (a major component of the motile parasite's cytoskeleton), are also eliminated from converting parasites. The high degree of sophistication of the metamorphosis that occurs at the onset of the liver-form development cascade suggests that the observed changes must be multifactorial. Among the mechanisms implicated in the elimination of sporozoite organelles, the degradative process called autophagy contributes to the remodelling of the parasite interior and the production of replicative liver forms. In a broader context, the importance of the role played by autophagy during the differentiation of protozoan parasites that cycle between insects and vertebrates is nowadays clearly emerging. An exciting prospect derived from these observations is that the parasite proteins involved in the autophagic process may represent new targets for drug development.

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Life-Cycle Assessment of Potential Algal Biodiesel Production in the United Kingdom: A Comparison of Raceways and Air-Lift Tubular Bioreactors

Energy & Fuels ◽

10.1021/ef1003123 ◽

2010 ◽

Vol 24 (7) ◽

pp. 4062-4077 ◽

Cited By ~ 390

Author(s):

Anna L. Stephenson ◽

Elena Kazamia ◽

John S. Dennis ◽

Christopher J. Howe ◽

Stuart A. Scott ◽

...

Keyword(s):

Life Cycle Assessment ◽

United Kingdom ◽

Life Cycle ◽

Biodiesel Production ◽

The United Kingdom ◽

Algal Biodiesel ◽

Air Lift

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Efficacy of four selective Trichoderma isolates as plant growth promoters in two peanut varieties

International Journal of Biological Research ◽

10.14419/ijbr.v4i2.6468 ◽

2016 ◽

Vol 4 (2) ◽

pp. 152

Author(s):

M. Kamaruzzaman ◽

M. M. Rahman ◽

M. S. Islam ◽

M. U. Ahmad

Keyword(s):

Plant Growth ◽

Pathogenic Fungi ◽

Control Treatment ◽

Growth Promoter ◽

Growth Promoters ◽

Higher Plant ◽

Potential Growth ◽

Trichoderma Species ◽

Wide Range ◽

Trichoderma Isolates

Trichoderma species are generally used as potential bio control agents against wide range of plant pathogenic fungi and some strains are reported to produce metabolites that enhance plant growth. In the current study we evaluated the four Trichoderma isolates viz. T. harzianum (ST5), T. viride (ST6), T. virens (ST7) and T. atroviride (ST9) including a control were tested as seed treatment against to find out a potential growth-promoter of Peanut. T. harzianum (ST5) gave maximum length and weight of shoot, weight of roots with pods, weight of pods and number of nodules per plant. T. viride (ST6) showed higher plant growth, nodulation and yield compared to T. virens (ST7) and T. atroviride (ST9). Minimum growth, yield and nodulation were observed with control treatment.

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Transcriptional regulation of metacyclic variant surface glycoprotein gene expression during the life cycle of Trypanosoma brucei.

Molecular and Cellular Biology ◽

10.1128/mcb.15.11.5945 ◽

1995 ◽

Vol 15 (11) ◽

pp. 5945-5956 ◽

Cited By ~ 33

Author(s):

S V Graham ◽

J D Barry

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Life Cycle ◽

Life Cycle Stage ◽

Surface Glycoprotein ◽

Variant Surface Glycoprotein ◽

Mammalian Host ◽

Dependent Manner ◽

African Trypanosomes ◽

Specific Subset

In antigenic variation in African trypanosomes, switching of the variant surface glycoprotein (VSG) allows evasion of the mammalian host immune response. Trypanosomes first express the VSG in the tsetse fly vector, at the metacyclic stage, in preparation for transfer into the mammal. In this life cycle stage, a small, specific subset (1 to 2%) of VSGs are activated, and we have shown previously that the system of activation and expression of metacyclic VSG (M-VSG) genes is very different from that used for bloodstream VSG genes (S.V. Graham, K.R. Matthews, P.G. Shiels, and J.D. Barry, Parasitology 101:361-367, 1990). Now we show that unlike other trypanosome genes including bloodstream VSG genes, M-VSG genes are expressed from promoters subject to exclusively transcriptional regulation in a life cycle stage-dependent manner. We have located an M-VSG gene promoter, and we demonstrate that it is specifically up-regulated at the metacyclic stage. This is the first demonstration of gene expression being regulated entirely at the level of transcription among the Kinetoplastida; all other protein-coding genes examined in these organisms are, at least partly, under posttranscriptional control. The distinctive mode of expression of M-VSG genes may be due to a stochastic mechanism for metacyclic VSG activation.

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