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1.
J Immunol Res ; 2022: 2574964, 2022.
Article in English | MEDLINE | ID: mdl-35155686

ABSTRACT

BACKGROUNDS: Infection and inflammation play an important role in prostate cancer (PCa) etiology and pathogenesis. However, the environmental drivers for PCa are not fully understood. METHODS: In a cross-sectional study, we analyzed circulating fungal microbiome in plasma samples from age and race-matched healthy control men (n = 34) and preoperative PCa patients (n = 31). RESULTS: The fungal community in the plasma exhibited differences between individuals with PCa and healthy controls according to the beta diversity; there was no difference in the alpha diversity. Moreover, the relative abundance of several fungi differed between the two study groups from the class to species levels. The most significant differences were Filobasidiales family, Pyronemataceae family, and Cryptococcus ater species, which were enriched in PCa patients compared to controls. The increased Bipolaris genus was associated with low prostate-specific antigen (PSA) levels, increased Sordariomycetes class was associated with severe pathological stage, and decreased Phoma herbarum species was associated with disease relapse, compared to corresponding controls. Several fungi from class to species levels were increased in the controls compared to patients. CONCLUSION: This is the first study to show plasma distinct fungal microbiome and its associations with PSA levels, relapse, and pathology stages in PCa patients.


Subject(s)
Bipolaris/physiology , Cryptococcus/physiology , Phoma/physiology , Prostatic Neoplasms/microbiology , Aged , Cross-Sectional Studies , Healthy Volunteers , Humans , Male , Microbiota/genetics , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Prostate-Specific Antigen/blood
2.
Food Microbiol ; 100: 103863, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34416963

ABSTRACT

In the present work, we evaluated the effects of a mixture of biocontrol agents against two toxigenic strains of Penicillium expansum isolated in Argentine Patagonia from pome fruits. The two strains, INTA-5 and INTA-10, were previusly selected among ten strains coming from the Alto Valle (Rio Negro-Argentina) for their high production of patulin. For the biocontrol, Kosakonia radicincitans, Cryptococcus laurentii, and Rhodosporidium fluviale were tested in vitro experiments on Potato Dextrose Agar (PDA) dishes against the INTA-5 and INTA-10 strains. The bacterium K. radicincitans and the yeast C. laurentii were selected to be used in a mixture due to their capacity to control the fungus and reduce the mycotoxin severely. In vitro assays with the mixture showed a high antagonism against P. expansum INTA-5 and INTA-10, at 21 d of incubation at 25 °C and a patulin reduction of 98%. The mixture of microorganisms was also effective in apples stored at 25 °C for 10 d and 4 °C for 30 d. At cold storage, the mixture controlled moderately the development of rot and decreased patulin concentration. At 25 °C, the pathogen's optimal growth temperature, the mixture of Biological Control Agent (BCAs) assured both the control of rot and decrease of patulin concentration. The combination of two microorganisms, with different requirements and abilities, resulted in a mix with a strong antagonism against P. expansum with the capability to decrease the patulin concentration. Treatment with the selected mixture could be a good option for controlling strains with different behaviours and in different environmental conditions.


Subject(s)
Antibiosis , Biological Control Agents/pharmacology , Cryptococcus/physiology , Enterobacteriaceae/physiology , Malus/microbiology , Patulin/biosynthesis , Penicillium/drug effects , Penicillium/metabolism , Plant Diseases/microbiology , Fruit/microbiology
3.
Int J Biol Macromol ; 181: 253-262, 2021 Jun 30.
Article in English | MEDLINE | ID: mdl-33775762

ABSTRACT

The synergistic effects of carboxymethylcellulose (CMC) combined with Cryptococcus laurentii FRUC DJ1 were studied on controlling green mould resulting from Penicillium digitatum in grapefruit fruit. The results indicate that both C. laurentii and the CMC treatment suppressed P. digitatum conidia germination. In addition, C. laurentii growth in vitro was not affected by low CMC concentrations, nevertheless, the biofilm of C. laurentii was enhanced. Compared with the control fruit, the grapefruit had a lower green mould in all treatments. Significantly synergistic effects were caused by combining C. laurentii and CMC on minimum decay incidence and lesion diameter. Combined treatment induced defence enzyme activities, including chitinase, ß-1,3-glucanase, peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase, together with disease tolerance-associated total phenol. Also, this combination inhibited the pathogen growth by adhered to the hyphae and reduced its infection in fruit wounds. Moreover, the commercial quality parameters in the combined treatment of C. laurentii and CMC, including weight loss, total soluble solids, ascorbic acid, and titratable acidity, were superior to single treatment. The combination of C. laurentii and CMC can not only control postharvest decay but also maintain fruit qualities. Thus, it can be used in grapefruit for commercial purposes.


Subject(s)
Carboxymethylcellulose Sodium/pharmacology , Citrus paradisi/microbiology , Cryptococcus/physiology , Penicillium/pathogenicity , Plant Diseases/microbiology , Biofilms/drug effects , Biofilms/growth & development , Citrus paradisi/drug effects , Citrus paradisi/enzymology , Citrus paradisi/ultrastructure , Cryptococcus/growth & development , Penicillium/classification , Phenols/metabolism
4.
Nat Rev Microbiol ; 19(7): 454-466, 2021 07.
Article in English | MEDLINE | ID: mdl-33558691

ABSTRACT

Cryptococcus spp., in particular Cryptococcus neoformans and Cryptococcus gattii, have an enormous impact on human health worldwide. The global burden of cryptococcal meningitis is almost a quarter of a million cases and 181,000 deaths annually, with mortality rates of 100% if infections remain untreated. Despite these alarming statistics, treatment options for cryptococcosis remain limited, with only three major classes of drugs approved for clinical use. Exacerbating the public health burden is the fact that the only new class of antifungal drugs developed in decades, the echinocandins, displays negligible antifungal activity against Cryptococcus spp., and the efficacy of the remaining therapeutics is hampered by host toxicity and pathogen resistance. Here, we describe the current arsenal of antifungal agents and the treatment strategies employed to manage cryptococcal disease. We further elaborate on the recent advances in our understanding of the intrinsic and adaptive resistance mechanisms that are utilized by Cryptococcus spp. to evade therapeutic treatments. Finally, we review potential therapeutic strategies, including combination therapy, the targeting of virulence traits, impairing stress response pathways and modulating host immunity, to effectively treat infections caused by Cryptococcus spp. Overall, understanding of the mechanisms that regulate anti-cryptococcal drug resistance, coupled with advances in genomics technologies and high-throughput screening methodologies, will catalyse innovation and accelerate antifungal drug discovery.


Subject(s)
Cryptococcosis/drug therapy , Cryptococcus/cytology , Cryptococcus/physiology , Antifungal Agents/pharmacology , Cell Wall/chemistry , Cell Wall/physiology , Cryptococcosis/immunology , Cryptococcosis/microbiology , Cryptococcus/chemistry , Cryptococcus/drug effects , Drug Resistance, Fungal , Echinocandins/pharmacology , Fungal Capsules/chemistry , Fungal Capsules/physiology , Fungal Polysaccharides/chemistry , Virulence Factors
5.
IUBMB Life ; 72(11): 2303-2312, 2020 11.
Article in English | MEDLINE | ID: mdl-32897638

ABSTRACT

The genus Cryptococcus comprises of more than 30 species. It consists of clinically significant pathogenic Cryptococcus neoformans/Cryptococcus gattii species complex comprising of a minimum of seven species. These pathogens cost more than 200,000 lives annually by causing cryptococcal meningoencephalitis. The evolution of the pathogenic species from closely related non-pathogenic species of the Cryptococcus amylolentus complex is of particular importance and several advances have been made to understand their phylogenetic and genomic relationships. The current review briefly describes the sexual reproduction process followed by an individual description of the members focusing on their key attributes and virulence mechanisms of the pathogenic species. A special section on phylogenetic studies is aimed at understanding the evolutionary divergence of pathogens from non-pathogens. Recent findings from our group pertaining to parameters affecting codon usage bias in six pathogenic and three non-pathogenic ancestral species and their corroboration with existing phylogenetic reports are also included in the current review.


Subject(s)
Biological Evolution , Codon Usage , Cryptococcosis/microbiology , Cryptococcus/classification , Cryptococcus/physiology , Animals , Cryptococcus/genetics , Humans
6.
Sci Rep ; 10(1): 9387, 2020 06 10.
Article in English | MEDLINE | ID: mdl-32523003

ABSTRACT

Cryptococcosis is a systemic infection and it may occur in immunocompromised and immunocompetent hosts. In order to better understand the clinical characteristics of patients with PC in different immune status, we retrospectively investigated the clinical, radiological, and treatment profiles of immunocompetent and immunocompromised patients with PC during a 10-year period (2008-2017). As a result, out of 136 patients, 94 (69.1%) were immunocompromised hosts. For the PC patients without CNS involvement, higher percentage of immunocompetent patients (39.5%, 15/38) had asymptomatic presentation than immunocompromised patients (6.3%, 3/48) (P < 0.05). Multiple pulmonary nodules (72.7%, 56/77), ground-glass attenuation/interstitial changes (94.4%, 17/18) and cavitation (88.6%, 31/35) were significantly frequent in immunocompromised patients (P < 0.05). A total of 47 patients were misdiagnosed as tuberculosis or tumors based on CT signs. PC was likely to be misdiagnosed as tuberculosis in immunocompromised patients (88.2%, 15/17), and tumor was more likely to be considered in immunocompetent patients (43.3%, 13/30). Immunocompetent patients accounted for 80% (24/30) of patients with definite diagnosis on surgical lung biopsy. Fluconazole monotherapy can achieve good clinical outcome in most PC patients without central nervous system (CNS) involvement (91.5%, 54/59). After 3 months of treatment, 92.7% (38/41) patients have improved imaging findings. In conclusion, PC has diverse imaging manifestations and it is easily misdiagnosed. Lobectomy should be carefully selected in immunocompetent patients with a single lung lesion. Fluconazole monotherapy is preferred for PC patients without CNS involvement.


Subject(s)
Asymptomatic Diseases/epidemiology , Central Nervous System/microbiology , Cryptococcosis/immunology , Cryptococcus/physiology , Diagnostic Errors/statistics & numerical data , Immunocompromised Host , Lung/pathology , Adult , Central Nervous System/pathology , China/epidemiology , Cryptococcosis/epidemiology , Cryptococcosis/therapy , Female , Fluconazole/therapeutic use , Humans , Immunocompetence , Lung/microbiology , Male , Middle Aged , Pneumonectomy , Retrospective Studies , Tomography, X-Ray Computed
7.
J Mycol Med ; 30(2): 100924, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32037102

ABSTRACT

Cryptococcus neoformans, an encapsulated fungal pathogen is evolving as a major threat to immune-compromised patients and rarely to healthy individuals also. The cell wall bound capsular polysaccharide, melanin pigment and biofilm formation are major virulence factors that are known to contribute to cryptococcal meningitis. In the present study, a furanone derivative, (E)-5-benzylidenedihydrofuran-2(3H)-one (compound-6) was evaluated against biofilm of seven different strains of C. neoformans in melanized and non-melanized condition. In addition, the efficacy of compound-6 in activation of TLR-2, opsonophagocytosis, and modulation of cytokine expression during phagocytosis were studied. During the biofilm study, we found that moderate capsule size favored biofilm formation. Interestingly, the minimum biofilm eradication concentration (MBEC0.5) of melanized biofilm was found to be achieved at 1- to 1.7-fold higher MBEC0.5 of non-melanized cells. The maximum eradication of 77% and 69% of non-melanized and melanized biofilm were observed. The capsule size was reduced to half of its size with marked changes in morphology. Furthermore, expression of TLR2, iNOS and pro-inflammatory cytokines such as TNF-α, IL-12, and IFN-γ were also facilitated by compound-6. The correlation analysis showed a positive correlation between phagocytosis and the expression of TLR-2, iNOS, IL-6, IL-12. Collectively, the significant effect of compound-6, anti-melanization activity, antibiofilmand effective immunomodulant could be an interesting dual strategy drug agonist against cryptococcal meningitis.


Subject(s)
Antifungal Agents/pharmacology , Biofilms/drug effects , Cryptococcus/drug effects , Opsonin Proteins/physiology , Phagocytosis/drug effects , Animals , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Bacterial Capsules/drug effects , Bacterial Capsules/physiology , Cells, Cultured , Cryptococcosis/immunology , Cryptococcosis/microbiology , Cryptococcus/physiology , Cryptococcus neoformans/drug effects , Cryptococcus neoformans/physiology , Furans/chemical synthesis , Furans/chemistry , Furans/pharmacology , Humans , Macrophages/drug effects , Macrophages/physiology , Melanins/metabolism , Meningitis, Cryptococcal/immunology , Meningitis, Cryptococcal/microbiology , Mice , Microbial Sensitivity Tests , Opsonin Proteins/metabolism
8.
PLoS One ; 15(2): e0228067, 2020.
Article in English | MEDLINE | ID: mdl-32023268

ABSTRACT

During our studies on asexual fungi colonizing herbaceous litter in northern Thailand, we discovered two new fungal species, viz. Dendryphion hydei and Torula hydei spp. nov. The latter are examined, and their morphological characters are described as well as their DNA sequences from ribosomal and protein coding genes are analysed to infer their phylogenetic relationships with extant fungi. Torula hydei is different from other similar Torula species in having tiny and catenate conidia. Dendryphion hydei can be distinguished from other similar Dendryphion species in having large conidiophores and subhyaline to pale olivaceous brown, 2-4(-5)-septate conidia. Multigene phylogenetic analyses of a combined LSU, SSU, TEF1-α, RPB2 and ITS DNA sequence dataset generated from maximum likelihood and Bayesian inference analyses indicate that T. hydei forms a distinct lineage and basal to T. fici. Dendryphion hydei forms a distinct lineage and basal to D. europaeum, D. comosum, D. aquaticum and D. fluminicola within Torulaceae (Pleosporales, Dothideomycetes).


Subject(s)
Ascomycota/genetics , Cryptococcus/genetics , Ascomycota/classification , Ascomycota/physiology , Bayes Theorem , Cryptococcus/classification , Cryptococcus/physiology , DNA, Fungal/chemistry , DNA, Fungal/metabolism , Phylogeny , Sequence Analysis, DNA , Thailand
9.
Sci Adv ; 5(12): eaaw9051, 2019 12.
Article in English | MEDLINE | ID: mdl-31840058

ABSTRACT

Epigenetic modifications play critical roles in inducing long-lasting immunological memory in innate immune cells, termed trained immunity. Whether similar epigenetic mechanisms regulate dendtritic cell (DC) function to orchestrate development of adaptive immunity remains unknown. We report that DCs matured with IFNγ and TNFα or matured in the lungs during invasive fungal infection with endogenous TNFα acquired a stable TNFα-dependent DC1 program, rendering them resistant to both antigen- and cytokine-induced alternative activation. TNFα-programmed DC1 had increased association of H3K4me3 with DC1 gene promoter regions. Furthermore, MLL1 inhibition blocked TNFα-mediated DC1 phenotype stabilization. During IFI, TNFα-programmed DC1s were required for the development of sustained TH1/TH17 protective immunity, and bone marrow pre-DCs exhibited TNFα-dependent preprogramming, supporting continuous generation of programmed DC1 throughout the infection. TNFα signaling, associated with epigenetic activation of DC1 genes particularly via H3K4me3, critically contributes to generation and sustenance of type 1/17 adaptive immunity and the immune protection against persistent infection.


Subject(s)
Cell Polarity , Cytoprotection , Dendritic Cells/metabolism , Epigenesis, Genetic , T-Lymphocytes/cytology , Tumor Necrosis Factor-alpha/metabolism , Animals , Cell Polarity/drug effects , Cellular Reprogramming/drug effects , Cryptococcus/drug effects , Cryptococcus/physiology , Cytoprotection/drug effects , Dendritic Cells/drug effects , Epigenesis, Genetic/drug effects , Female , Histone-Lysine N-Methyltransferase/metabolism , Histones/metabolism , Immunomodulation/drug effects , Lysine/metabolism , Methylation , Mice, Inbred CBA , Myeloid-Lymphoid Leukemia Protein/metabolism , Phenotype , Promoter Regions, Genetic/genetics , Suppression, Genetic/drug effects , T-Lymphocytes/drug effects , Th1 Cells/drug effects , Th1 Cells/immunology , Tumor Necrosis Factor-alpha/pharmacology
10.
Curr Neurol Neurosci Rep ; 19(10): 81, 2019 10 31.
Article in English | MEDLINE | ID: mdl-31673881

ABSTRACT

PURPOSE OF REVIEW: Defective cell-mediated immunity is a major risk factor for cryptococcosis, a fatal disease if untreated. Cryptococcal meningitis (CM), the main presentation of disseminated disease, occurs through hematogenous spread to the brain from primary pulmonary foci, facilitated by yeast virulence factors. We revisit remarkable recent improvements in the prevention, diagnosis and management of CM. RECENT FINDINGS: Cryptococcal antigen (CrAg), main capsular polysaccharide of Cryptococcus spp. is detectable in blood and cerebrospinal fluid of infected patients with point of care lateral flow assays. Recent World Health Organization guidelines recommend 7-day amphotericin B plus flucytosine, then 7-day high dose (1200 mg/day) fluconazole for induction treatment of HIV-associated CM. Management of raised intracranial pressure, a consequence of CM, should rely mainly on daily therapeutic lumbar punctures until normalisation. In HIV-associated CM, following introduction of antifungal therapy, (re)initiation of antiretroviral therapy should be delayed by 4-6 weeks to prevent immune reconstitution inflammatory syndrome, common in CM. CM is a fatal disease whose diagnosis has recently been simplified. Treatment should always include antifungal combination therapy and management of raised intracranial pressure. Screening for immune deficiency should be mandatory in all patients with cryptococcosis.


Subject(s)
Amphotericin B/therapeutic use , Cryptococcus/physiology , Fluconazole/therapeutic use , Flucytosine/therapeutic use , Meningitis, Cryptococcal , Antifungal Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , Drug Therapy, Combination , HIV Infections/complications , HIV Infections/drug therapy , Humans , Immunologic Deficiency Syndromes/diagnosis , Intracranial Hypertension/surgery , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/drug therapy , Meningitis, Cryptococcal/prevention & control , Risk Factors
11.
Genes (Basel) ; 10(10)2019 10 21.
Article in English | MEDLINE | ID: mdl-31640207

ABSTRACT

The impact of fungi on human and plant health is an ever-increasing issue. Recent studies have estimated that human fungal infections result in an excess of one million deaths per year and plant fungal infections resulting in the loss of crop yields worth approximately 200 million per annum. Sexual reproduction in these economically important fungi has evolved in response to the environmental stresses encountered by the pathogens as a method to target DNA damage. Meiosis is integral to this process, through increasing diversity through recombination. Mating and meiosis have been extensively studied in the model yeast Saccharomyces cerevisiae, highlighting that these mechanisms have diverged even between apparently closely related species. To further examine this, this review will inspect these mechanisms in emerging important fungal pathogens, such as Candida, Aspergillus, and Cryptococcus. It shows that both sexual and asexual reproduction in these fungi demonstrate a high degree of plasticity.


Subject(s)
Aspergillus/genetics , Candida/genetics , Cryptococcus/genetics , Genes, Mating Type, Fungal , Reproduction , Adaptation, Physiological , Aspergillus/physiology , Candida/physiology , Cryptococcus/physiology , Genetic Variation
12.
Annu Rev Genet ; 53: 417-444, 2019 12 03.
Article in English | MEDLINE | ID: mdl-31537103

ABSTRACT

Cryptococcus species utilize a variety of sexual reproduction mechanisms, which generate genetic diversity, purge deleterious mutations, and contribute to their ability to occupy myriad environmental niches and exhibit a range of pathogenic potential. The bisexual and unisexual cycles of pathogenic Cryptococcus species are stimulated by properties associated with their environmental niches and proceed through well-characterized signaling pathways and corresponding morphological changes. Genes governing mating are encoded by the mating-type (MAT) loci and influence pathogenesis, population dynamics, and lineage divergence in Cryptococcus. MAT has undergone significant evolutionary changes within the Cryptococcus genus, including transition from the ancestral tetrapolar state in nonpathogenic species to a bipolar mating system in pathogenic species, as well as several internal reconfigurations. Owing to the variety of established sexual reproduction mechanisms and the robust characterization of the evolution of mating and MAT in this genus, Cryptococcus species provide key insights into the evolution of sexual reproduction.


Subject(s)
Cryptococcus/physiology , Cryptococcus/pathogenicity , Genes, Mating Type, Fungal , Reproduction/physiology , Biological Evolution , Fungal Proteins/genetics , Fungal Proteins/metabolism , Genetics, Population , Host-Pathogen Interactions , Humans , Spores, Fungal/pathogenicity , Spores, Fungal/physiology
13.
Int J Infect Dis ; 88: 102-109, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31499210

ABSTRACT

BACKGROUND: Ventriculoperitoneal (VP) shunting in cryptococcal meningitis (CM) patients with high intracranial pressure (ICP) has been studied extensively. METHODS: A total of 74 CM patients with ICP were identified, including 27 patients with or without ventriculomegaly receiving VP shunting. RESULTS: Through retrospective analysis, there was an obvious decline in ICP as well as Cryptococcus count after VP shunting. Damage to the cranial nerves was improved after the surgery. For those patients receiving VP shunting, there was an obvious decline in ICP as well as Cryptococcus count, with less usage of mannitol. Hydrocephalus or ventriculomegaly was improved, and both the clearance time of Cryptococcus and the hospitalization time were shortened (p<0.05). The complications of VP shunting were not common. CONCLUSIONS: For patients diagnosed with CM and with apparent ICP, VP shunting can be considered regardless of whether there is damage to the cranial nerves or hydrocephaly.


Subject(s)
Intracranial Hypertension/surgery , Meningitis, Cryptococcal/surgery , Adult , Cryptococcus/genetics , Cryptococcus/isolation & purification , Cryptococcus/physiology , Female , Hospitalization , Humans , Hydrocephalus/microbiology , Hydrocephalus/surgery , Intracranial Hypertension/microbiology , Intracranial Hypertension/physiopathology , Intracranial Pressure , Male , Meningitis, Cryptococcal/microbiology , Meningitis, Cryptococcal/physiopathology , Middle Aged , Retrospective Studies , Ventriculoperitoneal Shunt
14.
Appl Environ Microbiol ; 85(21)2019 11 01.
Article in English | MEDLINE | ID: mdl-31444202

ABSTRACT

Yeasts form mutualistic interactions with insects. Hallmarks of this interaction include provision of essential nutrients, while insects facilitate yeast dispersal and growth on plant substrates. A phylogenetically ancient chemical dialogue coordinates this interaction, where the vocabulary, the volatile chemicals that mediate the insect response, remains largely unknown. Here, we used gas chromatography-mass spectrometry, followed by hierarchical cluster and orthogonal partial least-squares discriminant analyses, to profile the volatomes of six Metschnikowia spp., Cryptococcus nemorosus, and brewer's yeast (Saccharomyces cerevisiae). The yeasts, which are all found in association with insects feeding on foliage or fruit, emit characteristic, species-specific volatile blends that reflect the phylogenetic context. Species specificity of these volatome profiles aligned with differential feeding of cotton leafworm (Spodoptera littoralis) larvae on these yeasts. Bioactivity correlates with yeast ecology; phylloplane species elicited a stronger response than fruit yeasts, and larval discrimination may provide a mechanism for establishment of insect-yeast associations. The yeast volatomes contained a suite of insect attractants known from plant and especially floral headspace, including (Z)-hexenyl acetate, ethyl (2E,4Z)-deca-2,4-dienoate (pear ester), (3E)-4,8-dimethylnona-1,3,7-triene (DMNT), linalool, α-terpineol, ß-myrcene, or (E,E)-α-farnesene. A wide overlap of yeast and plant volatiles, notably floral scents, further emphasizes the prominent role of yeasts in plant-microbe-insect relationships, including pollination. The knowledge of insect-yeast interactions can be readily brought to practical application, as live yeasts or yeast metabolites mediating insect attraction provide an ample toolbox for the development of sustainable insect management.IMPORTANCE Yeasts interface insect herbivores with their food plants. Communication depends on volatile metabolites, and decoding this chemical dialogue is key to understanding the ecology of insect-yeast interactions. This study explores the volatomes of eight yeast species which have been isolated from foliage, from flowers or fruit, and from plant-feeding insects. These yeasts each release a rich bouquet of volatile metabolites, including a suite of known insect attractants from plant and floral scent. This overlap underlines the phylogenetic dimension of insect-yeast associations, which according to the fossil record long predate the appearance of flowering plants. Volatome composition is characteristic for each species, aligns with yeast taxonomy, and is further reflected by a differential behavioral response of cotton leafworm larvae, which naturally feed on foliage of a wide spectrum of broad-leaved plants. Larval discrimination may establish and maintain associations with yeasts and is also a substrate for designing sustainable insect management techniques.


Subject(s)
Herbivory/physiology , Insecta/microbiology , Larva/growth & development , Larva/microbiology , Yeasts/metabolism , Acyclic Monoterpenes , Animals , Cryptococcus/physiology , Cyclohexane Monoterpenes , Flowers , Fruit , Gas Chromatography-Mass Spectrometry , Host Microbial Interactions , Metabolome , Metschnikowia/physiology , Odorants , Pheromones , Phylogeny , Saccharomyces cerevisiae/physiology , Smell , Spodoptera/growth & development , Spodoptera/microbiology , Volatile Organic Compounds
15.
Bioorg Med Chem Lett ; 29(16): 2059-2063, 2019 08 15.
Article in English | MEDLINE | ID: mdl-31320146

ABSTRACT

Invasive fungal infections are one of the leading causes of nosocomial bloodstream infections with a limited treatment option. A series of derivatized spirooxindolo-pyrrolidine tethered indole and imidazole heterocyclic hybrids have been synthesized, and their antifungal activity against fungal strains were determined. Here we characterize the antifungal activity of a specific spirooxindolo-pyrrolidine hybrid, dubbed compound 9c, a spirooxindolo-pyrrolidine tethered imidazole synthesized with a 2-chloro and trifluoromethoxy substituent. The compound 9c exhibited no cytotoxicity against mammalian cell line at concentrations that inhibited fungal strains. Compound 9c also significantly inhibited the fungal hyphae and biofilm formation. Our results indicate that spirooxindolo-pyrrolidine heterocyclic hybrids potentially represent a broad class of chemical agents with promising antifungal potential.


Subject(s)
Antifungal Agents/pharmacology , Imidazoles/pharmacology , Indoles/pharmacology , Pyrrolidines/pharmacology , Spiro Compounds/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/toxicity , Biofilms/drug effects , Candida/drug effects , Candida/physiology , Cell Line, Tumor , Cryptococcus/drug effects , Cryptococcus/physiology , Humans , Imidazoles/chemical synthesis , Imidazoles/toxicity , Indoles/chemical synthesis , Indoles/toxicity , Microbial Sensitivity Tests , Pyrrolidines/chemical synthesis , Pyrrolidines/toxicity , Spiro Compounds/chemical synthesis , Spiro Compounds/toxicity
16.
Nat Commun ; 10(1): 2955, 2019 07 04.
Article in English | MEDLINE | ID: mdl-31273203

ABSTRACT

Dendritic cells (DCs), a vital component of the innate immune system, are considered to lack antigen specificity and be devoid of immunological memory. Strategies that can induce memory-like responses from innate cells can be utilized to elicit protective immunity in immune deficient persons. Here we utilize an experimental immunization strategy to modulate DC inflammatory and memory-like responses against an opportunistic fungal pathogen that causes significant disease in immunocompromised individuals. Our results show that DCs isolated from protectively immunized mice exhibit enhanced transcriptional activation of interferon and immune signaling pathways. We also show long-term memory-like cytokine responses upon subsequent challenge with the fungal pathogen that are abrogated with inhibitors of specific histone modifications. Altogether, our study demonstrates that immunization strategies can be designed to elicit memory-like DC responses against infectious disease.


Subject(s)
Dendritic Cells/immunology , Immunologic Memory , Animals , Cryptococcosis/immunology , Cryptococcosis/microbiology , Cryptococcus/physiology , Dendritic Cells/microbiology , Female , Histones/metabolism , Immunity, Innate , Inflammation/genetics , Inflammation/pathology , Interferon-gamma/metabolism , Lung/immunology , Lung/microbiology , Mice, Inbred BALB C , Phenotype , Protein Processing, Post-Translational , RNA, Messenger/genetics , RNA, Messenger/metabolism , Vaccination
17.
Sci Total Environ ; 673: 750-755, 2019 Jul 10.
Article in English | MEDLINE | ID: mdl-31003102

ABSTRACT

A process to produce both biodiesel and alginate in an integrated manner from a brown seaweed, Laminaria japonica, was established. Mannitol, a major carbon constituent in L. japonica, served to produce neutral lipids via the heterotrophic cultivation of an oleaginous yeast, Cryptococcus sp.; and simultaneously alginate, a high value product, was extracted to enhance the economic feasibility of the entire process. Only autoclave pretreatment, without need of any chemical agents, was enough to recover all the essential nutrients for the yeast cultivation. Specifically, it could recover 6.4 g L-1 of mannitol to a degree comparable to 6.6 g L-1 obtained by acid-aided pretreatment using 1.5% (v/v) of H2SO4. Maximum fatty acids methyl esters (FAME) content was 30.37% with FAME productivity of 0.56 g L-1 d-1, and the produced FAME could meet the biodiesel quality standards. Na2CO3-based method showed the best efficiency of alginate recovery, yielding 21.06% (w/w). This study supports that L. japonica can indeed be a promising low-cost feedstock for biodiesel production, and it is more so when a high-value product alginate is co-produced.


Subject(s)
Alginates/metabolism , Biofuels , Laminaria/physiology , Cryptococcus/physiology , Seaweed/physiology
18.
Med Mycol ; 57(2): 133-150, 2019 Feb 01.
Article in English | MEDLINE | ID: mdl-30329097

ABSTRACT

Pulmonary cryptococcosis is an important opportunistic invasive mycosis in immunocompromised patients, but it is also increasingly seen in immunocompetent patients. The main human pathogens are Cryptococcus neoformans and C. gattii, which have a worldwide distribution. In contrast to cryptococcal meningitis, pulmonary cryptococcosis is still underdiagnosed because of limitations in diagnostic tools. It can mimic lung cancer, pulmonary tuberculosis, bacterial pneumonia, and other pulmonary mycoses both clinically and radiologically. Pulmonary nodules are the most common radiological feature, but these are not specific to pulmonary cryptococcosis. The sensitivity of culture of respiratory samples for Cryptococcus is poor and a positive result may also reflect colonisation. Cryptococcal antigen (CrAg) with lateral flow device is a fast and sensitive test and widely used on serum and cerebrospinal fluid, but sera from patients with pulmonary cryptococcosis are rarely positive in the absence of disseminated disease. Detection of CrAg from respiratory specimens might assist the diagnosis of pulmonary cryptococcosis but there are very few data. Molecular detection techniques such as multiplex reverse transcription polymerase chain reaction (RT-PCR) could also provide better sensitivity but these still require validation for respiratory specimens. The first line of treatment for pulmonary cryptococcosis is fluconazole, or amphotericin B and flucytosine for those with central nervous system involvement. Pulmonary cryptococcosis worsens the prognosis of cryptococcal meningitis. In this review, we summarize the biological aspects of Cryptococcus and provide an update on the diagnosis and management of pulmonary cryptococcosis.


Subject(s)
Cryptococcosis/diagnosis , Cryptococcosis/pathology , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/pathology , Lung/pathology , Animals , Antifungal Agents/therapeutic use , Clinical Laboratory Techniques , Cryptococcosis/drug therapy , Cryptococcosis/prevention & control , Cryptococcus/isolation & purification , Cryptococcus/pathogenicity , Cryptococcus/physiology , Humans , Lung/microbiology , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/prevention & control , Prognosis , Risk Factors
19.
Microbiologyopen ; 8(6): e00746, 2019 06.
Article in English | MEDLINE | ID: mdl-30277315

ABSTRACT

Cryptococcal infection is a major cause of opportunistic infection in HIV/AID-infected peoples. We determined cryptococcal antigenemia and cryptococcal meningitis among antiretroviral therapy (ART) initiated and ART-naive HIV-infected peoples. A cross-sectional study was conducted at selected health facilities in Mekelle, Ethiopia. Blood was collected to determine CD4 and plasma cryptococcal antigen (CrAg). CSF CrAg and CSF culture and urease tests were also done. Socio-demographic and clinical data were collected using a structured questionnaire and clinical chart review. From the enrolled study participants, 267 study participants had complete data, of which, 137 (51%) were females. From the study participants, 140 (52%) and 127 (48%) were ART experienced and ART naïve, respectively. The prevalence of cryptococcal antigenemia was 9 (3.4%). All the study participants, except one (CD4 = 120 cells/mm3 ), had CD4 count less than 100 cells/mm3 . From CrAg-positive peoples, 6 (4.7%) were ART naïve. Five CrAg-positive peoples had cryptococcal meningitis. Being male, rural residence, and being hospitalized were associated with cryptococcal antigenemia. Cryptococcal infection poses a substantial risk of HIV-positive peoples. This study provides relevant data for CrAg screening interventions in patients with low CD4 cell counts.


Subject(s)
AIDS-Related Opportunistic Infections/microbiology , Anti-HIV Agents/administration & dosage , Cryptococcosis/microbiology , Cryptococcus/physiology , HIV Infections/drug therapy , AIDS-Related Opportunistic Infections/blood , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/immunology , Adult , Anti-HIV Agents/adverse effects , Antigens, Fungal/blood , CD4 Lymphocyte Count , Cross-Sectional Studies , Cryptococcosis/blood , Cryptococcosis/epidemiology , Cryptococcosis/immunology , Cryptococcus/classification , Cryptococcus/genetics , Cryptococcus/isolation & purification , Ethiopia/epidemiology , Female , Humans , Male , Middle Aged , Young Adult
20.
Food Chem ; 278: 240-247, 2019 Apr 25.
Article in English | MEDLINE | ID: mdl-30583368

ABSTRACT

This research aimed to investigate the roles of phytohormone ethylene in cherry tomato fruit immune response against gray mold caused by Botrytis cinerea. Pretreatment with antagonistic yeast Cryptococcus laurentii resulted in a significantly decreased disease incidence of B. cinerea infection, and accompanied by a burst of ethylene production in the whole fruit. Blocking the ethylene perception by adding 1-MCP (5 µL L-1 or greater) remarkably weaken the protection ability of fruit itself and suppressed the C. laurentii-stimulated host immune response. 5 µL L-1 1-MCP prefumigation decreased the expression of ethylene biosynthesis and perception related genes SlACO1, SlACS2, SlERF1, SlPti5 and SlMPK3, and ethylene production in C. laurentii treated fruit. Consequently, the expressions of SlCHI9, SlGlub, SlPAL3, SlPR1 and SlPR5 up-regulated by the yeast were all impaired to different degrees by the 1-MCP prefumigation. These findings demonstrate that ethylene contributes to fruit immunity and C. laurentii-mediated immune responses of cherry tomato.


Subject(s)
Botrytis/physiology , Cryptococcus/physiology , Ethylenes/metabolism , Fruit/microbiology , Plant Diseases/microbiology , Solanum lycopersicum/immunology , Solanum lycopersicum/microbiology , Ethylenes/biosynthesis , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Plant Diseases/immunology , Plant Growth Regulators/biosynthesis , Plant Growth Regulators/metabolism
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