HomeArt of LivingFungal Spores Hijack a...

Fungal Spores Hijack a Host Protein to Escape Death

 

F
ungal pathogens have emerged as a significant threat to human health as they become more prevalent and resistant to the handful of antifungal treatments available today.1 One of the toughest fungi to beat is Aspergillus fumigatus, a widespread mold that can cause life-threatening pulmonary infections in people with weakened immune systems.

A. fumigatus dodges the host immune system by sneaking into cells in membrane-enclosed vesicles known as phagosomes. These pathogen-containing vesicles are usually headed for degradation as the phagosomes mature and become more acidified. For A. fumigatus, though, intracellular extermination is not a done deal.

 

Scientists knew that the mold could interfere with the process of phagosome maturation; however, there was limited knowledge about the molecules used to set the fungal escape plan in motion. In a recent study, researchers discovered that A. fumigatus spores redirect fungus-containing phagosomes from a degradative to a non-degradative pathway by hijacking a human protein in those vesicles. They also found that transplant patients with a particular mutation in the gene that encodes the protein were less likely to develop invasive aspergillosis, a severe fungal infection with a high mortality rate among immunocompromised patients. The findings were published in the journal Cell Host & Microbe.2

Axel Brakhage, the scientific director of the Leibniz Institute for Natural Product Research and Infection Biology and study coauthor, has been interested in understanding how this fungus evades degradation inside the cell. His group previously found that a pigment present on the surface of A. fumigatus prevents phagosome maturation in immune cells.3 But they were surprised to find that some spore mutants lacking the pigment could still avoid phagocytic destruction, suggesting that the mold adopts an alternative intracellular escape strategy.

See also “Fungal Pathogens Flourish in the Pandemic’s Shadow”

To uncover A. fumigatus’s escape mechanism, the team assessed how the fungal spore proteins interacted with human lung epithelial cells, the body’s first line of defense against the mold. They showed that A. fumigatus spores use a surface protein, HscA, to bind to epithelial cells and that HscA was key to keeping the phagosomes in an immature state—less acidified vesicles that are not headed for degradation.

They next showed that HscA targets a small human protein found in phagosomes, which the researchers named p11. By interacting with p11, A. fumigatus spores alter the molecular marks on the phagosomes, excluding a mark for vesicle destruction and recruiting tags for phagosome recycling. In turn, this leads the vesicle to be released into the extracellular space, transferred to an adjacent cell, or to stay inside the cells.

For Scott Filler, a researcher at the University of California, Los Angeles, who was not involved in the study, the identification of HscA is a key finding. “This protein on the Aspergillus surface…basically stalls phagosome maturation,” he said.

Although epithelial lung cells are an important barrier against A. fumigatus, they are not specialized in killing pathogens as immune cells are. To investigate if the fungus would pull off its escape strategy in immune cells, the team repeated the experiments in macrophages and neutrophils. “We found basically the same findings; it is a general mechanism,” said Brakhage.

See also “Fungal DNA, Cells Found in Human Tumors”

To assess whether the in vitro findings were also clinically relevant, the researchers screened a group of stem cell transplant recipients and their corresponding donors for single nucleotide polymorphisms (SNP) in the p11 gene and evaluated their risk for developing invasive pulmonary aspergillosis (IPA). They found that a specific SNP located in a noncoding region of the p11 gene associated with a decreased risk for IPA. The fact that the researchers looked at patients to substantiate their in vitro findings makes the study stand out, said Filler. “It is very nice to go all the way from an in vitro model into basically human patients.”

The findings not only uncover the different components used by A. fumigatus to dodge intracellular destruction in the host’s cells, but they also provide clinical evidence that may help identify patients at greater risk for fungal infections who would benefit the most from antifungal treatments.

- A word from our sponsors -

spot_img

Most Popular

More from Author

Exploring the Legacy of Captain James Cook in ‘The Wide Wide Sea’

Introduction to Captain James Cook's Final Voyage In Hampton Sides' captivating book,...

Zhu Lin: The Queen of Drama Revealed in New Book

Introduction to Zhu Lin's Life A new book titled Zhu Lin, the Queen...

The National Book Critics Circle Awards: A Milestone with the First-Ever Nonfiction Longlist

The NBCC Celebrates 50 Years The National Book Critics Circle (NBCC) is...

National Book Critics Circle Awards: Celebrating the First-Ever Autobiography Longlist

Introduction to the National Book Critics Circle Awards The National Book Critics...

- A word from our sponsors -

spot_img

Read Now

Exploring the Idiosyncratic Characters in Flannery O’Connor’s Stories

Introduction to Flannery O'Connor's Unique Narratives Flannery O'Connor, a notable Southern writer, weaves expansive short stories featuring characters whose idiosyncratic behaviors reflect a deep sense of otherness. Her talent lies in creating memorable tales that not only entertain but also provoke thought. Among her works, the most recognized...

Exploring Themes of Family and Femininity in Tara Isabel Zambrano’s ‘Ruined a Little When We Are Born’

Introduction to Zambrano’s Work Tara Isabel Zambrano’s collection, Ruined a Little When We Are Born, is a compelling compendium of human experiences, blending elements of flash fiction and traditional storytelling. This slim volume encompasses over three dozen stories that resonate deeply with readers. Zambrano navigates themes of family, femininity,...

Hwang Seok-Yeong: A Testament to Youthful Vigor in Literature

The Ageless Spirit of Hwang Seok-Yeong Veteran South Korean novelist Hwang Seok-Yeong has captured the hearts of readers both young and old with his profound storytelling that resonates deeply with modern stresses. Despite being in his 70s when he authored his acclaimed novel, At Dusk, Hwang’s writing reflects...

Barack Obama’s 2024 Annual Reading List: A Journey Through Literature

Introduction to Obama's Reading List On December 20, former President Barack Obama shared his 2024 annual reading list on Instagram. This year’s selection includes ten thought-provoking titles, comprising both fiction and non-fiction. Topics range from love and art to economic growth and mental health issues, showcasing the breadth...

Unveiling Ronald Reagan: A Definitive Biography by Max Boot

Introduction to 'Reagan: His Life and Legend' In 2024, Max Boot's monumental biography, 'Reagan: His Life and Legend,' has emerged as an instant New York Times bestseller, capturing the attention of literary critics across the nation. This compelling work has not only earned a spot among the 50...

Exploring the Legacy of Captain James Cook in ‘The Wide Wide Sea’

Introduction to Captain James Cook's Final Voyage In Hampton Sides' captivating book, 'The Wide Wide Sea,' readers are immersed in the enthralling account of Captain James Cook's third and final voyage. This journey, which culminated in Cook's tragic death in Hawaii, serves as a reminder of the complex...

Zhu Lin: The Queen of Drama Revealed in New Book

Introduction to Zhu Lin's Life A new book titled Zhu Lin, the Queen of Drama has been launched, narrating the inspiring journey of a remarkable figure in Chinese theater. Authored by Zhao Hongfan, this work intricately weaves the life of Zhu Lin, often revered as the "queen of Chinese drama,"...

The National Book Critics Circle Awards: A Milestone with the First-Ever Nonfiction Longlist

The NBCC Celebrates 50 Years The National Book Critics Circle (NBCC) is marking a significant occasion with the announcement of its first-ever longlist for the nonfiction genre, celebrating its 50th anniversary. The longlist, which was released on December 18, highlights the organization's commitment to honoring exceptional writing in...

National Book Critics Circle Awards: Celebrating the First-Ever Autobiography Longlist

Introduction to the National Book Critics Circle Awards The National Book Critics Circle (NBCC) Awards, renowned for their distinction in literary recognition, have embarked on a significant milestone for 2024. In honor of their 50th anniversary, the NBCC has announced its inaugural longlist for the category of autobiography,...

Exploring the National Book Critics Circle Awards: A First-Ever Biography Longlist

Introduction to the NBCC Awards The National Book Critics Circle (NBCC) Awards are a prestigious event in the literary world, celebrating outstanding writing and fostering a national conversation about literature. This year marks a significant milestone as the NBCC has announced its first-ever longlist for the genre of...

British Library Expands Chinese Web Novels Collection

Introduction of New Titles On November 21, the British Library took a significant step in enhancing its collections by adding ten printed copies of popular Chinese web novels, which were originally published online. Among the notable titles included are "Lord of the Mysteries," "Soul Land," and "Joy of...

Shanghai Online Literature Week: A Milestone for Global Literary Exchange

Introduction to Shanghai Online Literature Week The third Shanghai International Online Literature Week, held from December 16 to 18, showcased significant advancements in the online literature genre. The event brought together writers and industry professionals from 16 countries, marking a pivotal moment for the dissemination of Chinese online...