Fungal resilience and host–pathogen interactions: Future perspectives and opportunities

Brown, Alistair J. P.

doi:10.1111/pim.12946

Cited by 8 publications

(4 citation statements)

References 274 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This effect was not evident in the evaluated ECM. The host microenvironment is in constant flux, in which the fungus must adapt and thrive [54]. The literature contains reports on the involvement of a two-component system and its downstream pathway, Hog1, in fungal signal transduction, which orchestrates responses to various stresses such as osmotic and oxidative stress, cell wall synthesis, virulence, cell adhesion, and morphogenesis [55][56][57][58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Polypeptides Targeting Paracoccidioides brasiliensis Drk1

Marcos,

de Oliveira,

Assato

et al. 2023

JoF

View full text Add to dashboard Cite

Considering the toxicity of conventional therapeutic approaches and the importance of precise mechanistic targets, it is important to explore signaling pathways implicated in fungal pathobiology. Moreover, treatment of paracoccidioidomycosis, a systemic mycosis caused by a dimorphic fungus, requires prolonged therapeutic regimens. Among the numerous factors underpinning the establishment of Paracoccidioides spp. infection, the capacity to transition from the mycelial to the yeast form is of pivotal importance. The Drk1 protein of Paracoccidioides brasiliensis likely plays a decisive role in this morphological shift and subsequent virulence. We identified peptides with affinity for the PbDrk1 protein using the phage-display method and assessed the effects of these peptides on P. brasiliensis. The peptides were found to inhibit the phase transition of P. brasiliensis. Furthermore, a substantial proportion of these peptides prevented adhesion to pneumocytes. Although these peptides may not possess inherent antifungal properties, they can augment the effects of certain antifungal agents. Notably, the cell wall architecture of P. brasiliensis appears to be modulated by peptide intervention, resulting in a reduced abundance of glycosylated proteins and lipids. These peptides were also evaluated for their efficacy in a Galleria mellonella model and shown to contribute to enhanced larval survival rates. The role of PbDrk1, which is notably absent in mammals, should be further investigated to improve the understanding of its functional role in P. brasiliensis, which may be helpful for designing novel therapeutic modalities.

show abstract

Section: Discussionmentioning

confidence: 99%

Polypeptides Targeting Paracoccidioides brasiliensis Drk1

Marcos,

de Oliveira,

Assato

et al. 2023

JoF

View full text Add to dashboard Cite

show abstract

“… 49 , 121 The human host environment poses significant stress for many microorganisms. 122 However, A. fumigatus demonstrates remarkable adaptability to various stressors, including high temperatures within deep tissues of the human body, 48 , 123 , 124 low pH conditions like those found in phagolysosomes, 49 , 125 low oxygen levels in tissues, 126 – 128 changes in osmotic pressure, 129 – 131 reactive oxygen species (ROS), 132 , 133 and microbiota. 134 , 135 Furthermore, A. fumigatus produces various hydrolytic enzymes, facilitating the acquisition of essential nutrients such as carbon, nitrogen, and ions (iron, copper, zinc, calcium, magnesium, and manganese) required for survival within the human body.…”

Section: Risk Factors For Cpamentioning

confidence: 99%

Chronic pulmonary aspergillosis: comprehensive insights into epidemiology, treatment, and unresolved challenges

Tashiro,

Takazono,

Izumikawa

2024

Therapeutic Advances in Infection

View full text Add to dashboard Cite

Chronic pulmonary aspergillosis (CPA) is a challenging respiratory infection caused by the environmental fungus Aspergillus. CPA has a poor prognosis, with reported 1-year mortality rates ranging from 7% to 32% and 5-year mortality rates ranging from 38% to 52%. A comprehensive understanding of the pathogen, pathophysiology, risk factors, diagnosis, surgery, hemoptysis treatment, pharmacological therapy, and prognosis is essential to manage CPA effectively. In particular, Aspergillus drug resistance and cryptic species pose significant challenges. CPA lacks tissue invasion and has specific features such as aspergilloma. The most critical risk factor for the development of CPA is pulmonary cavitation. Diagnostic approaches vary by CPA subtype, with computed tomography (CT) imaging and Aspergillus IgG antibodies being key. Treatment strategies include surgery, hemoptysis management, and antifungal therapy. Surgery is the curative option. However, reported postoperative mortality rates range from 0% to 5% and complications range from 11% to 63%. Simple aspergilloma generally has a low postoperative mortality rate, making surgery the first choice. Hemoptysis, observed in 50% of CPA patients, is a significant symptom and can be life-threatening. Bronchial artery embolization achieves hemostasis in 64% to 100% of cases, but 50% experience recurrent hemoptysis. The efficacy of antifungal therapy for CPA varies, with itraconazole reported to be 43–76%, voriconazole 32–80%, posaconazole 44–61%, isavuconazole 82.7%, echinocandins 42–77%, and liposomal amphotericin B 52–73%. Combinatorial treatments such as bronchoscopic triazole administration, inhalation, or direct injection of amphotericin B at the site of infection also show efficacy. A treatment duration of more than 6 months is recommended, with better efficacy reported for periods of more than 1 year. In anticipation of improvements in CPA management, ongoing advances in basic and clinical research are expected to contribute to the future of CPA management.

show abstract

“…Moreover, the ischemic phase can result in nutrient scarcity within the graft and surrounding tissues, affecting T-cell functionality ( 290 ). Lastly, fungal pathogens such as Candida and Aspergillus exploit host immune cells’ reliance on glycolysis in hypoxic conditions, evading immune clearance ( 291 ). Understanding these intricate interactions is crucial for enhancing our approach to fungal infections following transplantation.…”

Section: Fungal Infectionmentioning

confidence: 99%

Modulatory immune responses in fungal infection associated with organ transplant - advancements, management, and challenges

Elalouf,

Rosenfeld

2023

Front. Immunol.

View full text Add to dashboard Cite

Organ transplantation stands as a pivotal achievement in modern medicine, offering hope to individuals with end-stage organ diseases. Advancements in immunology led to improved organ transplant survival through the development of immunosuppressants, but this heightened susceptibility to fungal infections with nonspecific symptoms in recipients. This review aims to establish an intricate balance between immune responses and fungal infections in organ transplant recipients. It explores the fundamental immune mechanisms, recent advances in immune response dynamics, and strategies for immune modulation, encompassing responses to fungal infections, immunomodulatory approaches, diagnostics, treatment challenges, and management. Early diagnosis of fungal infections in transplant patients is emphasized with the understanding that innate immune responses could potentially reduce immunosuppression and promise efficient and safe immuno-modulating treatments. Advances in fungal research and genetic influences on immune-fungal interactions are underscored, as well as the potential of single-cell technologies integrated with machine learning for biomarker discovery. This review provides a snapshot of the complex interplay between immune responses and fungal infections in organ transplantation and underscores key research directions.

show abstract

Fungal resilience and host–pathogen interactions: Future perspectives and opportunities

Cited by 8 publications

References 274 publications

Polypeptides Targeting Paracoccidioides brasiliensis Drk1

Polypeptides Targeting Paracoccidioides brasiliensis Drk1

Chronic pulmonary aspergillosis: comprehensive insights into epidemiology, treatment, and unresolved challenges

Modulatory immune responses in fungal infection associated with organ transplant - advancements, management, and challenges

Contact Info

Product

Resources

About