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Updated: May 2, 2026
Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 15, 2011
Murine laminin binds to Histoplasma capsulatum. A possible mechanism of dissemination
J P McMahon1, J Wheat, M E Sobel
1Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
Abstract:
Histoplasmosis, an increasingly important opportunistic infection in immunosuppressed subjects, is characterized by hematogenous dissemination of the yeast from the lung. The mechanism of this dissemination is not fully understood. Laminin, the major glycoprotein of the extracellular matrix, is known to mediate the attachment of various invasive pathogens to host tissues. In the current study, laminin is demonstrated to bind to Histoplasma capsulatum in a rapid, specific, and saturable manner. Scatchard analysis with 125I-labeled laminin revealed an estimated 3.0 x 10(4) binding sites per yeast with an apparent Kd for laminin binding of 1.6 x 10(-9) M. Laminin binding to H. capsulatum was decreased from 62 +/- 1 to 17 +/- 1 ng (P < 0.001) in the presence of 3,000 nM of Ile-Lys-Val-Ala-Val, a pentapeptide within one major cell attachment site of laminin. A 50-kD H. capsulatum laminin-binding protein was demonstrated using an 125I-Ln blot of H. capsulatum cell wall proteins. The 50-kD protein is also recognized by antibodies directed at the 67-kD laminin receptor, suggesting they are related. This study proposes a possible mechanism for H. capsulatum attachment to laminin, an important first step required for the yeast to recognize and traverse the basement membrane.
Insights
Histoplasma capsulatum yeast binds to laminin, a key extracellular matrix protein, facilitating dissemination in opportunistic infections. A specific 50-kD protein on the yeast surface mediates this crucial interaction.
Area of Science:
- Mycology
- Infectious Diseases
- Cell Biology
Background:
- Histoplasmosis is a significant opportunistic infection in immunocompromised individuals.
- Hematogenous dissemination of Histoplasma yeast from the lungs is a hallmark of the disease.
- The precise mechanism of this dissemination remains incompletely understood.
Purpose of the Study:
- To investigate the interaction between Laminin and Histoplasma capsulatum.
- To elucidate the role of Laminin in the dissemination of Histoplasma.
- To identify potential molecular targets for controlling Histoplasma dissemination.
Main Methods:
- Radioligand binding assays using 125I-labeled laminin to quantify binding to H. capsulatum.
- Scatchard analysis to determine binding kinetics (Kd and number of binding sites).
- Peptide inhibition assays to assess the specificity of laminin binding.
- Western blotting (125I-Ln blot) to identify laminin-binding proteins on H. capsulatum cell walls.
Main Results:
- Laminin binds to H. capsulatum rapidly, specifically, and saturably.
- An estimated 3.0 x 10^4 binding sites per yeast with a Kd of 1.6 x 10^-9 M were found.
- A pentapeptide within a laminin cell attachment site significantly inhibited laminin binding.
- A 50-kD H. capsulatum laminin-binding protein was identified and appears related to the 67-kD laminin receptor.
Conclusions:
- Laminin binding to H. capsulatum is a specific, high-affinity interaction.
- A 50-kD yeast protein is involved in laminin binding, potentially mediating attachment.
- This interaction represents a potential mechanism for basement membrane recognition and traversal by Histoplasma yeast.
