scholarly journals What Are the Best Parents for Hybrid Progeny? An Investigation into the Human Pathogenic Fungus Cryptococcus

2021 ◽  
Vol 7 (4) ◽  
pp. 299
Author(s):  
Man You ◽  
Jianping Xu
Keyword(s):  
Pathogenic Fungus ◽  
Sequence Divergence ◽  
Hybrid Vigor ◽  
Phenotypic Trait ◽  
Hybrid Progeny ◽  
Melanin Production ◽  
Fluconazole Resistance ◽  
Human Pathogenic Fungus ◽  
Two Temperatures ◽  
The Relationship

Hybridization between more divergent organisms is likely to generate progeny with more novel genetic interactions and genetic variations. However, the relationship between parental genetic divergence and progeny phenotypic variation remains largely unknown. Here, using strains of the human pathogenic Cryptococcus, we investigated the patterns of such a relationship. Twenty-two strains with up to 15% sequence divergence were mated. Progeny were genotyped at 16 loci. Parental strains and their progeny were phenotyped for growth ability at two temperatures, melanin production at seven conditions, and susceptibility to the antifungal drug fluconazole. We observed three patterns of relationships between parents and progeny for each phenotypic trait, including (i) similar to one of the parents, (ii) intermediate between the parents, and (iii) outside the parental phenotypic range. We found that as genetic distance increases between parental strains, progeny showed increased fluconazole resistance and growth at 37 °C but decreased melanin production under various oxidative and nitrosative stresses. Our findings demonstrate that, depending on the traits, both evolutionarily more similar strains and more divergent strains may be better parents to generate progeny with hybrid vigor. Together, the results indicate the enormous potential of Cryptococcus hybrids in their evolution and adaptation to diverse conditions.

Fitness distribution and transgressive segregation across 40 environments in a hybrid progeny population of the human-pathogenic yeast Cryptococcus neoformans

Genome ◽  
2008 ◽  
Vol 51 (4) ◽  
pp. 272-281 ◽  
Author(s):  
Morvarid Shahid ◽  
Susan Han ◽  
Heather Yoell ◽  
Jianping Xu
Keyword(s):  
Cryptococcus Neoformans ◽  
Biological Effects ◽  
Pathogenic Fungus ◽  
Transgressive Segregation ◽  
Variable Number ◽  
Hybrid Progeny ◽  
Pathogenic Yeast ◽  
Human Fungal Pathogen ◽  
Different Temperatures ◽  
Human Pathogenic Fungus

The opportunistic human fungal pathogen Cryptococcus neoformans includes two varieties, C. neoformans var. grubii and C. neoformans var. neoformans, which correspond to serotypes A and D, respectively. Recent population genetic studies revealed that multiple natural hybridizations have occurred recently between these two divergent lineages. However, the biological effects of such hybridizations are little understood. In this study, we used colony size as a proxy for vegetative fitness to examine the phenotypic effects of hybridization between these two lineages in a laboratory cross. Two genetically diverged parental strains that differed in their growth at different temperatures and on different media as well as in their susceptibility to the common antifungal drug fluconazole were chosen. A total of 269 progeny were obtained and their vegetative growth was determined in 40 environments that differed in nutrients, temperature, and fluconazole concentration. Our analyses indicated little evidence for outbreeding depression or heterosis in the average vegetative fitness of the hybrid progeny population. The progeny, each of the three environmental variables, and their two-way, three-way, and four-way interactions all contributed significantly to the overall vegetative fitness variation. Interestingly, a variable number of progeny displayed evidence of transgressive segregation in vegetative fitness among the tested environments. Our study suggests that hybridization could play a significant role in the phenotypic evolution of this important human-pathogenic fungus.

scholarly journals Cryptococcus neoformans Capsular Polysaccharide and Exopolysaccharide Fractions Manifest Physical, Chemical, and Antigenic Differences

2007 ◽  
Vol 7 (2) ◽  
pp. 319-327 ◽  
Author(s):  
Susana Frases ◽  
Leonardo Nimrichter ◽  
Nathan B. Viana ◽  
Antonio Nakouzi ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Capsular Polysaccharide ◽  
Pathogenic Fungus ◽  
Structural Features ◽  
Isolation Techniques ◽  
Antigenic Properties ◽  
Mass Size ◽  
Human Pathogenic Fungus ◽  
Culture Supernatants ◽  
The Relationship

ABSTRACT The human pathogenic fungus Cryptococcus neoformans has a large polysaccharide (PS) capsule and releases copious amounts of PS into cultures and infected tissues. The capsular PS is a major virulence factor that can elicit protective antibody responses. PS recovered from culture supernatants has historically provided an ample and convenient source of material for structural and immunological studies. Two major assumptions in such studies are that the structural features of the exopolysaccharide material faithfully mirror those of capsular PS and that the isolation methods do not change PS properties. However, a comparison of exopolysaccharide made by two isolation techniques with capsular PS stripped from cells with gamma radiation or dimethyl sulfoxide revealed significant differences in glycosyl composition, mass, size, charge, viscosity, circular-dichroism spectra, and reactivity with monoclonal antibodies. Our results strongly suggest that exopolysaccharides and capsular PS are structurally different. A noteworthy finding was that PS made by cetyltrimethylammonium bromide precipitation had a larger mass and a different conformation than PS isolated by concentration and filtration, suggesting that the method most commonly used to purify glucuronoxylomannan alters the PS. Hence, the method used to isolate PS can significantly influence the structural and antigenic properties of the product. Our findings have important implications for current views of the relationship between capsular PS and exopolysaccharides, for the generation of PS preparations suitable for immunological studies, and for the formulation of PS-based vaccines for the prevention of cryptococcosis.

scholarly journals Expression Patterns in Reductive Iron Assimilation and Functional Consequences during Phagocytosis of Lichtheimia corymbifera, an Emerging Cause of Mucormycosis

2021 ◽  
Vol 7 (4) ◽  
pp. 272
Author(s):  
Felicia Adelina Stanford ◽  
Nina Matthias ◽  
Zoltán Cseresnyés ◽  
Marc Thilo Figge ◽  
Mohamed I. Abdelwahab Hassan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Iron Uptake ◽  
Intracellular Transport ◽  
Pathogenic Fungus ◽  
Expression Patterns ◽  
Iron Depletion ◽  
Iron Assimilation ◽  
Human Pathogenic Fungus ◽  
Hyphal Formation ◽  
Yeast Mutants

Iron is an essential micronutrient for most organisms and fungi are no exception. Iron uptake by fungi is facilitated by receptor-mediated internalization of siderophores, heme and reductive iron assimilation (RIA). The RIA employs three protein groups: (i) the ferric reductases (Fre5 proteins), (ii) the multicopper ferroxidases (Fet3) and (iii) the high-affinity iron permeases (Ftr1). Phenotyping under different iron concentrations revealed detrimental effects on spore swelling and hyphal formation under iron depletion, but yeast-like morphology under iron excess. Since access to iron is limited during pathogenesis, pathogens are placed under stress due to nutrient limitations. To combat this, gene duplication and differential gene expression of key iron uptake genes are utilized to acquire iron against the deleterious effects of iron depletion. In the genome of the human pathogenic fungus L. corymbifera, three, four and three copies were identified for FRE5, FTR1 and FET3 genes, respectively. As in other fungi, FET3 and FTR1 are syntenic and co-expressed in L. corymbifera. Expression of FRE5, FTR1 and FET3 genes is highly up-regulated during iron limitation (Fe-), but lower during iron excess (Fe+). Fe- dependent upregulation of gene expression takes place in LcFRE5 II and III, LcFTR1 I and II, as well as LcFET3 I and II suggesting a functional role in pathogenesis. The syntenic LcFTR1 I–LcFET3 I gene pair is co-expressed during germination, whereas LcFTR1 II- LcFET3 II is co-expressed during hyphal proliferation. LcFTR1 I, II and IV were overexpressed in Saccharomyces cerevisiae to represent high and moderate expression of intracellular transport of Fe3+, respectively. Challenge of macrophages with the yeast mutants revealed no obvious role for LcFTR1 I, but possible functions of LcFTR1 II and IVs in recognition by macrophages. RIA expression pattern was used for a new model of interaction between L. corymbifera and macrophages.

scholarly journals Fructose Induces Fluconazole Resistance in Candida albicans through Activation of Mdr1 and Cdr1 Transporters

2021 ◽  
Vol 22 (4) ◽  
pp. 2127
Author(s):  
Jakub Suchodolski ◽  
Anna Krasowska
Keyword(s):  
Candida Albicans ◽  
Multidrug Resistance ◽  
Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
De Novo ◽  
Pathogenic Fungus ◽  
Serum Levels ◽  
Efflux Transporters ◽  
Fluconazole Resistance ◽  
Green Fluorescent

Candida albicans is a pathogenic fungus that is increasingly developing multidrug resistance (MDR), including resistance to azole drugs such as fluconazole (FLC). This is partially a result of the increased synthesis of membrane efflux transporters Cdr1p, Cdr2p, and Mdr1p. Although all these proteins can export FLC, only Cdr1p is expressed constitutively. In this study, the effect of elevated fructose, as a carbon source, on the MDR was evaluated. It was shown that fructose, elevated in the serum of diabetics, promotes FLC resistance. Using C. albicans strains with green fluorescent protein (GFP) tagged MDR transporters, it was determined that the FLC-resistance phenotype occurs as a result of Mdr1p activation and via the increased induction of higher Cdr1p levels. It was observed that fructose-grown C. albicans cells displayed a high efflux activity of both transporters as opposed to glucose-grown cells, which synthesize Cdr1p but not Mdr1p. Additionally, it was concluded that elevated fructose serum levels induce the de novo production of Mdr1p after 60 min. In combination with glucose, however, fructose induces Mdr1p production as soon as after 30 min. It is proposed that fructose may be one of the biochemical factors responsible for Mdr1p production in C. albicans cells.

The Effect of Mismatch Repair and Heteroduplex Formation on Sexual Isolation in Bacillus

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Jacek Majewski ◽  
Frederick M Cohan
Keyword(s):  
Mismatch Repair ◽  
Wild Type Strain ◽  
Resistance Mechanism ◽  
Sequence Divergence ◽  
Sexual Isolation ◽  
Wild Type ◽  
Exponential Relationship ◽  
Dna Strands ◽  
The Relationship ◽  
Heteroduplex Formation

AbstractIn Bacillus transformation, sexual isolation is known to be an exponential function of the sequence divergence between donor and recipient. Here, we have investigated the mechanism under which sequence divergence results in sexual isolation. We tested the effect of mismatch repair by comparing a wild-type strain and an isogenic mismatch-repair mutant for the relationship between sexual isolation and sequence divergence. Mismatch repair was shown to contribute to sexual isolation but was responsible for only a small fraction of the sexual isolation observed. Another possible mechanism of sexual isolation is that more divergent recipient and donor DNA strands have greater difficulty forming a heteroduplex because a region of perfect identity between donor and recipient is required for initiation of the heteroduplex. A mathematical model showed that this heteroduplex-resistance mechanism yields an exponential relationship between sexual isolation and sequence divergence. Moreover, this model yields an estimate of the size of the region of perfect identity that is comparable to independent estimates for Escherichia coli. For these reasons, and because all other mechanisms of sexual isolation may be ruled out, we conclude that resistance to heteroduplex formation is predominantly responsible for the exponential relationship between sexual isolation and sequence divergence in Bacillus transformation.

scholarly journals The CDC42 Homolog of the Dimorphic FungusPenicillium marneffei Is Required for Correct Cell Polarization during Growth but Not Development

2001 ◽  
Vol 183 (11) ◽  
pp. 3447-3457 ◽  
Author(s):  
Kylie J. Boyce ◽  
Michael J. Hynes ◽  
Alex Andrianopoulos
Keyword(s):  
Cell Shape ◽  
Pathogenic Fungus ◽  
Cell Polarization ◽  
Dominant Negative ◽  
Yeast Cells ◽  
Polarized Growth ◽  
Temperature Dependent ◽  
Human Pathogenic Fungus ◽  
Rho Family

ABSTRACT The opportunistic human pathogenic fungus Penicillium marneffei is dimorphic and is thereby capable of growth either as filamentous multinucleate hyphae or as uninucleate yeast cells which divide by fission. The dimorphic switch is temperature dependent and requires regulated changes in morphology and cell shape. Cdc42p is a Rho family GTPase which in Saccharomyces cerevisiae is required for changes in polarized growth during mating and pseudohyphal development. Cdc42p homologs in higher organisms are also associated with changes in cell shape and polarity. We have cloned a highly conserved CDC42 homolog from P. marneffeinamed cflA. By the generation of dominant-negative and dominant-activated cflA transformants, we have shown that CflA initiates polarized growth and extension of the germ tube and subsequently maintains polarized growth in the vegetative mycelium. CflA is also required for polarization and determination of correct cell shape during yeast-like growth, and active CflA is required for the separation of yeast cells. However, correct cflAfunction is not required for dimorphic switching and does not appear to play a role during the generation of specialized structures during asexual development. In contrast, heterologous expression ofcflA alleles in Aspergillus nidulansprevented conidiation.

scholarly journals The capsule ofCryptococcus neoformansmodulates phagosomal pH through its acid-base properties

2018 ◽  
Author(s):  
Carlos M. De Leon-Rodriguez ◽  
Man Shun Fu ◽  
M. Osman Corbali ◽  
Radames J.B. Cordero ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Capsular Polysaccharide ◽  
Glucuronic Acid ◽  
Pathogenic Fungus ◽  
Weak Acid ◽  
Phagocytic Cells ◽  
Acid Base ◽  
Encapsulated Cells ◽  
Human Pathogenic Fungus ◽  
Base Properties

AbstractPhagosomal acidification is a critical cellular mechanism for the inhibition and killing of ingested microbes by phagocytic cells. The acidic environment activates microbicidal proteins and creates an unfavorable environment for the growth of many microbes. Consequently, numerous pathogenic microbes have developed strategies for countering phagosomal acidification through various mechanisms that include interference with phagosome maturation. The human pathogenic fungusCryptococcus neoformansresides in acidic phagosome after macrophage ingestion that actually provides a favorable environment for replication since the fungus replicates faster at acidic pH. We hypothesized that the glucuronic acid residues in the capsular polysaccharide had the capacity to affect phagosome acidity through their acid-base properties. A ratiometric fluorescence comparison of imaged phagosomes containingC. neoformansto those containing beads showed that the latter were significantly more acidic. Similarly, phagosomes containing non-encapsulatedC. neoformanscells were more acidic than those containing encapsulated cells. Acid-base titrations of isolatedC. neoformanspolysaccharide revealed that it behaves as a weak acid with maximal buffering capacity around pH 4-5. We interpret these results as indicating that the glucuronic acid residues in theC. neoformanscapsular polysaccharide can buffer phagosomal acidification. Interference with phagosomal acidification represents a new function for the cryptococcal capsule in virulence and suggests the importance of considering the acid-base properties of microbial capsules in the host-microbe interaction for other microbes with charged residues in their capsules.ImportanceCryptococcus neoformansis the causative agent of cryptococcosis, a devastating fungal disease that affects thousands of individuals worldwide. This fungus has the capacity to survive inside phagocytic cells, which contributes to persistence of infection and dissemination. One of the major mechanisms of host phagocytes is to acidify the phagosomal compartment after ingestion of microbes. This study shows that the capsule ofC. neoformanscan interfere with full phagosomal acidification by serving as a buffer.

Sign in / Sign up

Export Citation Format

Share Document