Virulence Regulation and Drug-Resistance Mechanism of Fungal Infection

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 8716

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Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Piazzale Aldo Moro, 00185 Roma, Italy
Interests: drug resistance; biofilm; cell wall proteins; Candida spp.; Malassezia spp.; fungal infections
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Dear Colleagues,

Human fungal pathogens are a commonly underestimated cause of severe diseases associated with high morbidity and mortality. Like other pathogens, their survival and growth in the host, as well as subsequent host damage, is thought to be mediated by virulence factors which set them apart from harmless microbes. Fungi have a remarkable capacity to evolve resistance to antimicrobial agents, threatening the efficacy of the limited arsenal of antimicrobials. Currently, the treatment of fungal infections in humans is limited to the use of a few classes of antifungal drugs. Several studies report that the presence or expression of virulence traits is related to resistance to antimicrobials. Some suggest these relations are antagonistic, while others report enhanced resistance in isolates with high levels of virulence factors. Additionally, the literature indicates that inhibitors of specific virulence may be good therapeutic alternatives for the treatment of fungal infections.

In this Special Issue of Microorganisms, we invite you to send contributions, in the form of original research or review papers, that report the most recent, advanced methods of study concerning any aspects of the expression of virulence factors, in particular in strains of fungi that areresistant to drugs. Such topics might include studies on biofilm formation in resistant strains, or the description of the molecular change of virulence factors in different environments.

Prof. Dr. Letizia Angiolella
Guest Editor

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Keywords

  • drug resistance
  • yeast
  • mould
  • biofilm
  • dimorphism
  • proteinase
  • phospholipase

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Published Papers (3 papers)

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Editorial

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5 pages, 199 KiB  
Editorial
Virulence Regulation and Drug-Resistance Mechanism of Fungal Infection
by Letizia Angiolella
Microorganisms 2022, 10(2), 409; https://doi.org/10.3390/microorganisms10020409 - 10 Feb 2022
Cited by 8 | Viewed by 1915
Abstract
In this issue, I propose promising developments in the field of the mechanism of virulence factors that can be linked to antifungal resistance [...] Full article

Research

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19 pages, 3110 KiB  
Article
Modulation of Virulence-Associated Traits in Aspergillus fumigatus by BET Inhibitor JQ1
by Anastasia Orekhova, Marta De Angelis, Andrea Cacciotti, Massimo Reverberi, Dante Rotili, Alessandra Giorgi, Virginia Protto, Graziana Bonincontro, Francesco Fiorentino, Victor Zgoda, Antonello Mai, Anna Teresa Palamara and Giovanna Simonetti
Microorganisms 2022, 10(11), 2292; https://doi.org/10.3390/microorganisms10112292 - 18 Nov 2022
Cited by 2 | Viewed by 1767
Abstract
Aspergillus fumigatus is a disease-causing, opportunistic fungus that can establish infection due to its capacity to respond to a wide range of environmental conditions. Secreted proteins and metabolites, which play a critical role in fungal–host interactions and pathogenesis, are modulated by epigenetic players, [...] Read more.
Aspergillus fumigatus is a disease-causing, opportunistic fungus that can establish infection due to its capacity to respond to a wide range of environmental conditions. Secreted proteins and metabolites, which play a critical role in fungal–host interactions and pathogenesis, are modulated by epigenetic players, such as bromodomain and extraterminal domain (BET) proteins. In this study, we evaluated the in vitro and in vivo capability of the BET inhibitor JQ1 to modulate the extracellular proteins and virulence of A. fumigatus. The abundance of 25 of the 76 extracellular proteins identified through LC-MS/MS proteomic analysis changed following JQ1 treatment. Among them, a ribonuclease, a chitinase, and a superoxide dismutase were dramatically downregulated. Moreover, the proteomic analysis of A. fumigatus intracellular proteins indicated that Abr2, an intracellular laccase involved in the last step of melanin synthesis, was absent in the JQ1-treated group. To investigate at which level this downregulation occurred and considering the ability of JQ1 to modulate gene expression we checked the level of ABR2, Chitinase, and Superoxide dismutase mRNA expression by qRT-PCR. Finally, the capacity of JQ1 to reduce the virulence of A. fumigatus has been proved using Galleria mellonella larvae, which are an in vivo model to evaluate fungal virulence. Overall, the promising activity exhibited by JQ1 suggests that A. fumigatus is sensitive to BET inhibition and BET proteins may be a viable target for developing antifungal agents. Full article
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Review

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20 pages, 1483 KiB  
Review
Antibodies to Combat Fungal Infections: Development Strategies and Progress
by Ali A. Rabaan, Amal H. Alfaraj, Amer Alshengeti, Abdulsalam Alawfi, Sara Alwarthan, Mashael Alhajri, Amal H. Al-Najjar, Mona A. Al Fares, Mustafa A. Najim, Souad A. Almuthree, Sultan T. AlShurbaji, Fadwa S. Alofi, Bashayer M. AlShehail, Buthina AlYuosof, Ahlam Alynbiawi, Suha A. Alzayer, Nawal Al Kaabi, Wesam A. Abduljabbar, Zakiyah A. Bukhary and Ahmed S. Bueid
Microorganisms 2023, 11(3), 671; https://doi.org/10.3390/microorganisms11030671 - 6 Mar 2023
Cited by 4 | Viewed by 4201
Abstract
The finding that some mAbs are antifungal suggests that antibody immunity may play a key role in the defense of the host against mycotic infections. The discovery of antibodies that guard against fungi is a significant advancement because it gives rise to the [...] Read more.
The finding that some mAbs are antifungal suggests that antibody immunity may play a key role in the defense of the host against mycotic infections. The discovery of antibodies that guard against fungi is a significant advancement because it gives rise to the possibility of developing vaccinations that trigger protective antibody immunity. These vaccines might work by inducing antibody opsonins that improve the function of non-specific (such as neutrophils, macrophages, and NK cells) and specific (such as lymphocyte) cell-mediated immunity and stop or aid in eradicating fungus infections. The ability of antibodies to defend against fungi has been demonstrated by using monoclonal antibody technology to reconsider the function of antibody immunity. The next step is to develop vaccines that induce protective antibody immunity and to comprehend the mechanisms through which antibodies mediate protective effects against fungus. Full article
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