Structural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections

Cruz, Melissa R.; Cristy, Shane A.; Guha, Shantanu; Cesare, Giuseppe Buda De; Evdokimova, E.; Sánchez, Hiram; Borek, Dominika; Miramón, Pedro; Yano, Junko; Fidel, Paul L.; Savchenko, Alexei; Andes, David R.; Stogios, P.J.; Lorenz, Michael; Garsin, Danielle A.

doi:10.1038/s41467-022-33613-1

Cited by 20 publications

(28 citation statements)

References 61 publications

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“…Interestingly, it has been reported that the bacteriocin enterocin O16 is an E. faecalis virulence factor in Drosophila ( 33 ). Enterocin O16 is also known as EntV, which is heat resistant and able to kill some lactobacilli strain as well as to inhibit the hyphal growth, the virulence, and the biofilm formation of Candida albicans ( 34 – 36 ).…”

Section: Resultsmentioning

confidence: 99%

A Toll pathway effector protects Drosophila specifically from distinct toxins secreted by a fungus or a bacterium

Huang

Lou

Liu

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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The Drosophila systemic immune response against many Gram-positive bacteria and fungi is mediated by the Toll pathway. How Toll-regulated effectors actually fulfill this role remains poorly understood as the known Toll-regulated antimicrobial peptide (AMP) genes are active only against filamentous fungi and not against Gram-positive bacteria or yeasts. Besides AMPs, two families of peptides secreted in response to infectious stimuli that activate the Toll pathway have been identified, namely Bomanins and peptides derived from a polyprotein precursor known as Baramicin A (BaraA). Unexpectedly, the deletion of a cluster of 10 Bomanins phenocopies the Toll mutant phenotype of susceptibility to infections. Here, we demonstrate that BaraA is required specifically in the host defense against Enterococcus faecalis and against the entomopathogenic fungus Metarhizium robertsii , albeit the fungal burden is not altered in BaraA mutants. BaraA protects the fly from the action of distinct toxins secreted by these Gram-positive and fungal pathogens, respectively, Enterocin V and Destruxin A. The injection of Destruxin A leads to the rapid paralysis of flies, whether wild type (WT) or mutant. However, a larger fraction of wild-type than BaraA flies recovers from paralysis within 5 to 10 h. BaraAs' function in protecting the host from the deleterious action of Destruxin is required in glial cells, highlighting a resilience role for the Toll pathway in the nervous system against microbial virulence factors. Thus, in complement to the current paradigm, innate immunity can cope effectively with the effects of toxins secreted by pathogens through the secretion of dedicated peptides, independently of xenobiotics detoxification pathways.

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Section: Resultsmentioning

confidence: 99%

A Toll pathway effector protects Drosophila specifically from distinct toxins secreted by a fungus or a bacterium

Huang

Lou

Liu

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…The active form of EntV is 68 amino acids [ 60 ], which per se does not exhibit antifungal activity, inhibits C. albicans biofilm formation both in vitro and in vivo [ 61 ]. In a recent study aimed at optimizing its potential anti- Candida therapeutic the authors identified a shorter 12-mer peptide derived from EntV which maintained the inhibitory activity, including against Candida biofilms [ 62 ].…”

Section: The Futurementioning

confidence: 99%

Antifungal therapy of Candida biofilms: Past, present and future

Ajetunmobi

Badali

Romo

et al. 2023

Biofilm

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“…In addition, the role of antimicrobial peptides (AMPs) in treating IFDs have been well investigated; for example, peptides HIF-1α and LL-37 can inhibit C . albicans colonization [ 20 ]. Overall, these advances in fungal immunotherapies hold great promise for improving the treatment of fungal infections, especially in patients with weakened immune systems.…”

Section: Antifungal Immunotherapy In Invasive Fungal Infectionmentioning

confidence: 99%

Advances in the treatment of invasive fungal disease

Zhang

Bills

2023

PLoS Pathog

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With over 300 million severe cases and 1.5 million deaths annually, invasive fungal diseases (IFDs) are a major medical burden and source of global morbidity and mortality. The World Health Organization (WHO) recently released the first-ever fungal priority pathogens list including 19 fungal pathogens, considering the perceived public health importance. Most of the pathogenic fungi are opportunistic and cause diseases in patients under immunocompromised conditions such as HIV infection, cancer, chemotherapy, transplantation, and immune suppressive drug therapy. Worryingly, the morbidity and mortality caused by IFDs are continuously on the rise due to the limited available antifungal therapies, the emergence of drug resistance, and the increase of population that is vulnerable to IFDs. Moreover, the COVID-19 pandemic worsened IFDs as a globe health threat as it predisposes the patients to secondary life-threatening fungi. In this mini-review, we provide a perspective on the advances and strategies for combating IFDs with antifungal therapies.

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Structural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections

Cited by 20 publications

References 61 publications

A Toll pathway effector protects Drosophila specifically from distinct toxins secreted by a fungus or a bacterium

A Toll pathway effector protects Drosophila specifically from distinct toxins secreted by a fungus or a bacterium

Antifungal therapy of Candida biofilms: Past, present and future

Advances in the treatment of invasive fungal disease

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