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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Cholesterol-dependent attachment of human respiratory cells by Bordetella pertussis
Yanina Lamberti1, Jimena Alvarez Hayes, Maria L Perez Vidakovics
1CINDEFI (UNLP, CONICET La Plata), School of Science, La Plata University, La Plata, Argentina.
Abstract:
Bordetella pertussis is a re-emerging human respiratory pathogen whose infectious process is not fully understood, hampering the design of effective vaccines. The nature of bacterial attachment to host cells is a key event in the outcome of the infection. However, host cell receptors involved in B. pertussis colonization of the respiratory tract are still under investigation. Here, we report that cholesterol-rich domains are involved in B. pertussis adhesion to epithelial cells. Treatment of A549 cells with cholesterol-sequestering drugs such as methyl-beta-cyclodextrin, nystatin, or filipin resulted in a significant decrease of B. pertussis attachment. Confocal laser microscopy studies showed B. pertussis associated with cholesterol-rich domains. Accordingly, B. pertussis was found in detergent-resistant membrane domain fractions isolated from bacterial-infected A549 cells. Our results indicate a main role of filamentous hemagglutinin, an environmentally regulated virulence factor, in this interaction, and a specific affinity for cholesterol, one of the major components of tracheal secretions, which might additionally contribute to the effective colonization of the respiratory tract.
Insights
Bordetella pertussis attaches to respiratory epithelial cells via cholesterol-rich domains. Filamentous hemagglutinin mediates this interaction, crucial for pertussis colonization and vaccine development.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- Bordetella pertussis is a re-emerging respiratory pathogen.
- Understanding bacterial attachment is key to combating pertussis.
- Host cell receptors for B. pertussis colonization are not fully identified.
Purpose of the Study:
- To investigate the role of host cell cholesterol in B. pertussis adhesion.
- To identify specific bacterial factors involved in cholesterol-mediated attachment.
Main Methods:
- Treatment of A549 epithelial cells with cholesterol-sequestering drugs.
- Confocal laser microscopy to visualize bacterial association with cholesterol-rich domains.
- Isolation of detergent-resistant membrane domains from infected cells.
Main Results:
- Cholesterol-sequestering drugs significantly reduced B. pertussis attachment.
- B. pertussis was observed within cholesterol-rich membrane domains.
- Filamentous hemagglutinin (FHA) was identified as a key factor mediating attachment to cholesterol.
Conclusions:
- Cholesterol-rich domains are critical for B. pertussis adhesion to epithelial cells.
- Filamentous hemagglutinin plays a major role in this cholesterol-dependent interaction.
- This interaction may contribute to respiratory tract colonization by B. pertussis.
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