Aspergillus fumigatus CalA binds to integrin α5β1 and mediates host cell invasion

Hong Liu1, Mark J Lee2, Norma V Solis1

  • 1Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.

Nature Microbiology
|November 15, 2016
PubMed

Insights

The fungal pathogen Aspergillus fumigatus uses its surface protein CalA to invade host cells by triggering endocytosis. Targeting CalA shows promise for treating invasive pulmonary aspergillosis.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Cell Biology

Background:

  • Aspergillus fumigatus is an opportunistic fungal pathogen.
  • It invades pulmonary epithelial and vascular endothelial cells via induced endocytosis.
  • The precise mechanism of this invasion is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism of Aspergillus fumigatus invasion.
  • To identify key fungal factors mediating host cell entry.
  • To evaluate CalA as a potential therapeutic target for invasive pulmonary aspergillosis.

Main Methods:

  • Investigated the role of the thaumatin-like protein CalA in A. fumigatus invasion.
  • Examined CalA's interaction with host cell integrin α5β1.
  • Assessed the virulence of a ΔcalA deletion mutant in corticosteroid-treated mice.
  • Evaluated the efficacy of anti-CalA antibodies in a murine model of invasive pulmonary aspergillosis.

Main Results:

  • CalA is expressed on the A. fumigatus cell surface and mediates invasion of epithelial and endothelial cells.
  • CalA interacts with host integrin α5β1, inducing endocytosis.
  • A ΔcalA mutant exhibited significantly reduced virulence in mice, with improved survival and lower fungal burden.
  • Anti-CalA antibody pretreatment enhanced survival in a murine invasive pulmonary aspergillosis model.

Conclusions:

  • A. fumigatus CalA acts as an invasin, interacting with host integrin α5β1 to induce endocytosis and promote fungal virulence.
  • CalA is a promising immunotherapeutic target for invasive pulmonary aspergillosis.

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.8K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.4K
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
5.4K
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
5.9K
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
4.5K
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
3.3K