Lung and gut microbiomes in pulmonary aspergillosis: Exploring adjunctive therapies to combat the disease

Cai, Liuyang; Gao, Peigen; Wang, Zeyu; Dai, Chenyang; Ye, Ning; İlkit, Macit; Xue, Xiaochun; Xiao, Jinzhou; Chen, Chang

doi:10.3389/fimmu.2022.988708

Cited by 7 publications

(6 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Triazole resistance in A. fumigatus is becoming prevalent on a global scale, increasing the risk of treatment failure and mortality ( 37 ). Triazole resistance can emerge when genetic diversity occurs in the offspring of Aspergillus species and any triazole-containing environment ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Succinylation modification provides new insights for the treatment of immunocompromised individuals with drug-resistant Aspergillus fumigatus infection

Chen

Meng

et al. 2023

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Invasive Aspergillus fumigatus infection poses a serious threat to global human health, especially to immunocompromised individuals. Currently, triazole drugs are the most commonly used antifungals for aspergillosis. However, owing to the emergence of drug-resistant strains, the effect of triazole drugs is greatly restricted, resulting in a mortality rate as high as 80%. Succinylation, a novel post-translational modification, is attracting increasing interest, although its biological function in triazole resistance remains unclear. In this study, we initiated the screening of lysine succinylation in A. fumigatus. We discovered that some of the succinylation sites differed significantly among strains with unequal itraconazole (ITR) resistance. Bioinformatics analysis showed that the succinylated proteins are involved in a broad range of cellular functions with diverse subcellular localizations, the most notable of which is cell metabolism. Further antifungal sensitivity tests confirmed the synergistic fungicidal effects of dessuccinylase inhibitor nicotinamide (NAM) on ITR-resistant A. fumigatus. In vivo experiments revealed that treatment with NAM alone or in combination with ITR significantly increased the survival of neutropenic mice infected with A. fumigatus. In vitro experiments showed that NAM enhanced the killing effect of THP-1 macrophages on A. fumigatus conidia. Our results suggest that lysine succinylation plays an indispensable role in ITR resistance of A. fumigatus. Dessuccinylase inhibitor NAM alone or in combination with ITR exerted good effects against A. fumigatus infection in terms of synergistic fungicidal effect and enhancing macrophage killing effect. These results provide mechanistic insights that will aid in the treatment of ITR-resistant fungal infections.

show abstract

Section: Discussionmentioning

confidence: 99%

Succinylation modification provides new insights for the treatment of immunocompromised individuals with drug-resistant Aspergillus fumigatus infection

Chen

Meng

et al. 2023

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Life 2023, 13, 1017 9 of 22 gut-lung mycobiome axis [155][156][157][158][159]. The overgrowth of C. albicans and intestinal bacteria caused by oral antibiotic therapy in mice results in the production of prostaglandin E2 (PGE2) and promotes M2 macrophage polarization in the lungs [160].…”

Section: Some Studies Have Shown the Prominent Interactions Between I...mentioning

confidence: 99%

“…The crosstalk between C. albicans and A. fumigatus has caused the modulation of Th17 in the lung and airway inflammation responses [155]. It can be concluded that the constant inhalation of A. fumigatus alone is not enough to cause allergic reactions such as in ABPA [156]. Gut dysbiosis is required, and plays an important role in the pathogenesis of fungal allergic diseases in the lung [156,160].…”

Section: Some Studies Have Shown the Prominent Interactions Between I...mentioning

confidence: 99%

See 1 more Smart Citation

The Fungal and Bacterial Interface in the Respiratory Mycobiome with a Focus on Aspergillus spp.

Antariksa

Nurwidya

Zaini

et al. 2023

Life

View full text Add to dashboard Cite

The heterogeneity of the lung microbiome and its alteration are prevalently seen among chronic lung diseases patients. However, studies to date have primarily focused on the bacterial microbiome in the lung rather than fungal composition, which might play an essential role in the mechanisms of several chronic lung diseases. It is now well established that Aspergillus spp. colonies may induce various unfavorable inflammatory responses. Furthermore, bacterial microbiomes such as Pseudomonas aeruginosa provide several mechanisms that inhibit or stimulate Aspergillus spp. life cycles. In this review, we highlighted fungal and bacterial microbiome interactions in the respiratory tract, with a focus on Aspergillus spp.

show abstract

“…Furthermore, A. fumigatus can produce a variety of virulence factors such as gliotoxin, which influence pathogenesis [ 4 ]. Lastly, it has been proposed that the pulmonary microbiome influences the severity of infections caused by A. fumigatus [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

The Transcriptome Response to Azole Compounds in Aspergillus fumigatus Shows Differential Gene Expression across Pathways Essential for Azole Resistance and Cell Survival

Hokken,

Coolen,

Steenbreker

et al. 2023

JoF

View full text Add to dashboard Cite

The opportunistic pathogen Aspergillus fumigatus is found on all continents and thrives in soil and agricultural environments. Its ability to readily adapt to novel environments and to produce billions of spores led to the spread of azole-resistant A. fumigatus across the globe, posing a threat to many immunocompromised patients, including critically ill patients with severe influenza or COVID-19. In our study, we sought to compare the adaptational response to azoles from A. fumigatus isolates that differ in azole susceptibility and genetic background. To gain more insight into how short-term adaptation to stressful azole compounds is managed through gene expression, we conducted an RNA-sequencing study on the response of A. fumigatus to itraconazole and the newest clinically approved azole, isavuconazole. We observed many similarities in ergosterol biosynthesis up-regulation across isolates, with the exception of the pan-azole-resistant isolate, which showed very little differential regulation in comparison to other isolates. Additionally, we found differential regulation of membrane efflux transporters, secondary metabolites, iron metabolism, and various stress response and cell signaling mechanisms.

show abstract

Lung and gut microbiomes in pulmonary aspergillosis: Exploring adjunctive therapies to combat the disease

Cited by 7 publications

References 81 publications

Succinylation modification provides new insights for the treatment of immunocompromised individuals with drug-resistant Aspergillus fumigatus infection

Succinylation modification provides new insights for the treatment of immunocompromised individuals with drug-resistant Aspergillus fumigatus infection

The Fungal and Bacterial Interface in the Respiratory Mycobiome with a Focus on Aspergillus spp.

The Transcriptome Response to Azole Compounds in Aspergillus fumigatus Shows Differential Gene Expression across Pathways Essential for Azole Resistance and Cell Survival

Contact Info

Product

Resources

About