Crossover between the control of fungal pathogens in medicine and the wider environment and the threat of anti‐fungal resistance

The developing resistance in fungi has become a key challenge, which is being faced nowadays with the available antifungal agents in the market. Further search for novel compounds from different sources has been explored to meet this problem. The current review describes and highlights recent advancement in the antifungal drug aspects from plant and marine based sources. The current available antifungal agents act on specific targets on the fungal cell wall, like ergosterol synthesis, chitin biosynthesis, sphingolipid synthesis, glucan synthesis etc. We discuss some of the important anti-fungal agents like azole, polyene and allylamine classes that inhibit the ergosterol biosynthesis. Echinocandins inhibit β-1, 3 glucan synthesis in the fungal cell wall. The antifungals poloxins and nikkomycins inhibit fungal cell wall component chitin. Apart from these classes of drugs, several combinatorial therapies have been carried out to treat diseases due to fungal resistance. Recently, many antifungal agents derived from plant and marine sources showed potent activity. The renewed interest in plant and marine derived compounds for the fungal diseases created a new way to treat these resistant strains which are evident from the numerous literature publications in the recent years. Moreover, the compounds derived from both plant and marine sources showed promising results against fungal diseases. Altogether, this review article discusses the current antifungal agents and highlights the plant and marine based compounds as a potential promising antifungal agents.

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Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity

PLoS Pathogens ◽

10.1371/journal.ppat.1009324 ◽

2021 ◽

Vol 17 (3) ◽

pp. e1009324

Author(s):

Lucas dos Santos Dias ◽

Hannah E. Dobson ◽

Brock Kingstad Bakke ◽

Gregory C. Kujoth ◽

Junfeng Huang ◽

...

Keyword(s):

Infectious Diseases ◽

Influenza A ◽

Fungal Pathogens ◽

Animal Studies ◽

Structural Basis ◽

Viral Immunity ◽

Mucosal Vaccination ◽

Clinical Observations ◽

Protective Antibodies ◽

Anti Fungal

The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge.

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A Novel Strategy to Identify Haematology Patients at High Risk of Developing Aspergillosis

Frontiers in Immunology ◽

10.3389/fimmu.2021.780160 ◽

2021 ◽

Vol 12 ◽

Author(s):

James S. Griffiths ◽

P. Lewis White ◽

Aiysha Thompson ◽

Diogo M. da Fonseca ◽

Robert J. Pickering ◽

...

Keyword(s):

High Risk ◽

Disease Risk ◽

Low Risk ◽

Fungal Resistance ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

Negative Results ◽

Risk Patients ◽

Haematology Patients ◽

Anti Fungal

Invasive Aspergillosis (IA), typically caused by the fungus Aspergillus fumigatus, is a leading cause of morbidity and mortality in immunocompromised patients. IA remains a significant burden in haematology patients, despite improvements in the diagnosis and treatment of Aspergillus infection. Diagnosing IA is challenging, requiring multiple factors to classify patients into possible, probable and proven IA cohorts. Given the low incidence of IA, using negative results as exclusion criteria is optimal. However, frequent false positives and severe IA mortality rates in haematology patients have led to the empirical use of toxic, drug-interactive and often ineffective anti-fungal therapeutics. Improvements in IA diagnosis are needed to reduce unnecessary anti-fungal therapy. Early IA diagnosis is vital for positive patient outcomes; therefore, a pre-emptive approach is required. In this study, we examined the sequence and expression of four C-type Lectin-like receptors (Dectin-1, Dectin-2, Mincle, Mcl) from 42 haematology patients and investigated each patient’s anti-Aspergillus immune response (IL-6, TNF). Correlation analysis revealed novel IA disease risk factors which we used to develop a pre-emptive patient stratification protocol to identify haematopoietic stem cell transplant patients at high and low risk of developing IA. This stratification protocol has the potential to enhance the identification of high-risk patients whilst reducing unnecessary treatment, minimizing the development of anti-fungal resistance, and prioritising primary disease treatment for low-risk patients.

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Anti-fungal activities of constituents from Uvaria scheffleri and Artabotrys brachypetalus

Journal of Agricultural Sciences Belgrade ◽

10.2298/jas0601079o ◽

2006 ◽

Vol 51 (1) ◽

pp. 79-86 ◽

Cited By ~ 1

Author(s):

A.C. Odebode ◽

S.A. Jonker ◽

C.C. Joseph ◽

S.W. Wachira

Keyword(s):

Fusarium Solani ◽

Radial Growth ◽

Fungal Pathogens ◽

Dry Weight ◽

Stem Bark ◽

Inhibitory Effect ◽

In Vitro Bioassay ◽

Botryodiplodia Theobromae ◽

Anti Fungal

The anti-fungal activity of schefflone, a mixture of dimmer, 3,5 dimethoxy carvacrol and annonaceous acetogenin, extracted from stem-bark and root of Uvaria scheffleri and Artabotrys bruchypetalus against Fusarium solani, Botryodiplodia theobromae, Asperillus niger and Aspergillus flavus was determined. An in-vitro bioassay showed that the minimum inhibitory effect of the compounds to the fungal pathogens occurred at 200 ppm in both radial growth and mycelia dry weight measurements. Acetogenin from A brachypetalus had a very strong anti-fungal effect on all the test fungi. The effects of the compounds were more pronounced on F solani than on the other. The bioassay methods also play a significant role in the sensitivity of the samples on the pathogens. .

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HYD3, a conidial hydrophobin of the fungal entomopathogen Metarhizium acridum induces the immunity of its specialist host locust

10.1101/2020.06.13.149757 ◽

2020 ◽

Author(s):

Zeyuan Jiang ◽

Petros Ligoxygakis ◽

Yuxian Xia

Keyword(s):

Fungal Pathogens ◽

Galleria Mellonella ◽

Locusta Migratoria ◽

Fungal Resistance ◽

Immune Recognition ◽

Metarhizium Acridum ◽

Humoral And Cellular Immunity ◽

Fungal Entomopathogen ◽

Conidial Surface ◽

Locusta Migratoria Manilensis

AbstractConidial hydrophobins in fungal pathogens of plants1,2, insects3,4, and humans5,6 are required for fungal attachment and are associated with high virulence. They are believed to contribute to the pathogenesis of infection by preventing immune recognition5,6. Here, we refute this generalisation offering a more nuanced analysis. We show that MacHYD3, a hydrophobin located on the conidial surface of the specialist entomopathogenic fungus Metarhizium acridum, activates specifically the humoral and cellular immunity of its own host insect, Locusta migratoria manilensis (Meyen) but not that of other non-host insects. When topically applied to the cuticle, purified MacHYD3 improved the resistance of locusts to both specialist and generalist fungal pathogens but had no effect on the fungal resistance of other insects, including Spodoptera frugiperda and Galleria mellonella. Hydrophobins extracted from the generalist fungal pathogens M. anisopliae and Beauveria bassiana had no effect on the resistance of locusts to fungal infection. Thus, the host locust has evolved to recognize the conidial hydrophobin of its specialist fungal pathogen, whereas conidial hydrophobins from generalist fungi are able to evade recognition. Our results distinguish the immunogenic potential of conidial hydrophobins between specialist and generalist fungi.

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Pattern of anti-fungal resistance among vulvovaginal candida species

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2020.08.128 ◽

2020 ◽

Vol 223 (6) ◽

pp. 965

Author(s):

A.M. Boyd-Tressler ◽

MengYao ◽

G. Procop ◽

T. Goje

Keyword(s):

Candida Species ◽

Fungal Resistance ◽

Anti Fungal

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Resistance Induction in Plants by a Brassinosteroid-Containing Extract of Lychnis viscaria L.

Zeitschrift für Naturforschung C ◽

10.1515/znc-2000-7-813 ◽

2000 ◽

Vol 55 (7-8) ◽

pp. 552-559 ◽

Cited By ~ 13

Author(s):

Udo Roth ◽

Annette Friebe ◽

Heide Schnabl

Keyword(s):

Plant Extract ◽

Fungal Pathogens ◽

Time Course ◽

Protein Patterns ◽

Mycelium Growth ◽

Enhanced Resistance ◽

Sds Page ◽

Defence Responses ◽

Lychnis Viscaria ◽

Anti Fungal

Abstract Resistance inducing effects of an extract of Lychnis viscaria L. seeds, containing different brassinosteroids (BR), were investigated. Application of aqueous solutions in concentrations from 0.5 to 10 mg/l (dry wt. of extract) resulted in an enhanced resistance of tobacco, cucumber and tomato to viral and fungal pathogens of up to 36% compared with water-treated control plants. No direct anti-fungal effects in mycelium growth assays with Phytophthora infestans could be observed. After treatment and inoculation with powdery mildew a stimulation of different PR-proteins (ca. + 20% for peroxidase, + 30% for chitinase and up to + 68% for β-1,3-glucanase) in cucumber was found. A chitinase in gel-electrophoresisassay showed a stronger induction of a distinct isoform under the same conditions. Time course of peroxidase induction and changes of apoplastic protein patterns revealed by SDS-PAGE indicated an earlier triggering of defence responses after plant-extract treatment and pathogen attack, probably being responsible for the increased resistance. Involvement of the brassinosteroids in the plant extract is discussed to elicit or mediate the activation of defence-mechanisms.

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High prevalence of non-albicans yeasts and detection of anti-fungal resistance in the oral flora of patients with advanced cancer

Palliative Medicine ◽

10.1191/0269216303pm793oa ◽

2003 ◽

Vol 17 (6) ◽

pp. 477-481 ◽

Cited By ~ 67

Author(s):

J Bagg ◽

M P Sweeney ◽

M AO Lewis ◽

M S Jackson ◽

D Coleman ◽

...

Keyword(s):

Advanced Cancer ◽

Fungal Resistance ◽

Oral Flora ◽

High Prevalence ◽

Anti Fungal

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Identification of Genes for Wheat Fungal Resistance Using Bioinformatics Techniques

10.36462/h.biosci.20185 ◽

2018 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Ahmed E. Nassar ◽

Khaled H. Mousa ◽

Ahmed A. Madbouly ◽

Shafik D. Ibrahim ◽

Alsamman M. Alsamman

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Fungal Pathogens ◽

Gene Annotation ◽

Average Length ◽

Amino Acid Sequences ◽

Protein Domain ◽

Fungal Resistance ◽

Domain Identification ◽

Cereal Grain

For the majority of world populations, wheat (Triticum aestivum L.) would be the first essential and economic cereal grain crop. Pests and pathogens in both rich and developing countries are constantly threatening wheat production and sustainable development. Multiple gene pathways were recorded to share an association with fungal pathogens with wheat biological resistance. Our aim to use such tools in order to detect and classify fungal resistance genes in wheat through sequence alignment, protein domain identification and phylogenetic analysis. In addition the introduction for restriction fragment length polymorphism (RFLP) for such genes in the new primer database. Approximately 138 sequences of DNA were recovered from the wheat genome by aligning 3845 anti-fungal amino acids through tblastn tool. The NCBI blastn online tool used to detect sequences with functional genes, where 92 genes have been detected. The total number of nucleotides was 48385, where the smallest DNA sequence have 302 bp and the longest contains 977 bp with an average length of 525.9 bp per sequence. The wheat chromosomes 3D, and 4B have the highest number of sequences (9) followed by chromosomes 3B (7) and 3A(6), where wheat genomes A, B and D have 30, 35 and 27 genes, respectively. Five different amino acids motifs have been revealed among studied wheat amino acid sequences. The gene annotation tools used to infer studied amino acid gene annotation. Amino acid sequences belongs to lectin, kinase, tyrosine-protein kinase (STK), thaumatin, and cysteine-rich repeats representing 2, 9, 8, 19, 23 genes respectively, in addition to 31 hypothetical genes. The proteins chemical content have been assessed through 16 different amino acid chemical and physical characteristics.

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Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond

PLoS Pathogens ◽

10.1371/journal.ppat.1010073 ◽

2021 ◽

Vol 17 (12) ◽

pp. e1010073

Author(s):

Rafael W. Bastos ◽

Luana Rossato ◽

Gustavo H. Goldman ◽

Daniel A. Santos

Keyword(s):

Fungal Pathogens ◽

Fungal Infections ◽

Resistance Mechanism ◽

Antifungal Resistance ◽

Antifungal Drugs ◽

Fungal Resistance ◽

Cross Resistance ◽

Term Therapy ◽

Prior History ◽

Plant Materials

Fungal infections are underestimated threats that affect over 1 billion people, and Candida spp., Cryptococcus spp., and Aspergillus spp. are the 3 most fatal fungi. The treatment of these infections is performed with a limited arsenal of antifungal drugs, and the class of the azoles is the most used. Although these drugs present low toxicity for the host, there is an emergence of therapeutic failure due to azole resistance. Drug resistance normally develops in patients undergoing azole long-term therapy, when the fungus in contact with the drug can adapt and survive. Conversely, several reports have been showing that resistant isolates are also recovered from patients with no prior history of azole therapy, suggesting that other routes might be driving antifungal resistance. Intriguingly, antifungal resistance also happens in the environment since resistant strains have been isolated from plant materials, soil, decomposing matter, and compost, where important human fungal pathogens live. As the resistant fungi can be isolated from the environment, in places where agrochemicals are extensively used in agriculture and wood industry, the hypothesis that fungicides could be driving and selecting resistance mechanism in nature, before the contact of the fungus with the host, has gained more attention. The effects of fungicide exposure on fungal resistance have been extensively studied in Aspergillus fumigatus and less investigated in other human fungal pathogens. Here, we discuss not only classic and recent studies showing that environmental azole exposure selects cross-resistance to medical azoles in A. fumigatus, but also how this phenomenon affects Candida and Cryptococcus, other 2 important human fungal pathogens found in the environment. We also examine data showing that fungicide exposure can select relevant changes in the morphophysiology and virulence of those pathogens, suggesting that its effect goes beyond the cross-resistance.

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