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Published on: March 26, 2012
LFchimera protects HeLa cells from invasion by Yersinia spp. in vitro
Tjitske Sijbrandij1, Antoon J Ligtenberg1, Kamran Nazmi1
1Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands.
Abstract:
Yersinia pestis is the causative agent of plague. As adequate antibiotic treatment falls short and currently no effective vaccine is available, alternative therapeutic strategies are needed. In order to contribute to solving this problem we investigated the therapeutic potential of the peptide construct LFchimera against the safer-to-handle Y. pestis simulants Yersinia enterocolitica and Yersinia pseudotuberculosis in vitro. LFchimera is a heterodimeric peptide construct mimicking two antimicrobial domains of bovine lactoferrin, i.e. lactoferrampin and lactoferricin. LFchimera has been shown to be a potent antimicrobial peptide against a variety of bacteria in vitro and in vivo. Also Y. enterocolitica and Y. pseudotuberculosis have been shown to be susceptible for LFchimera in vitro. As Yersiniae spp. adhere to and invade host cells upon infection, we here investigated the effects of LFchimera on these processes. It was found that LFchimera has the capacity to inhibit host-cell invasion by Yersiniae spp. in vitro. This effect appeared to be host-cell mediated, not bacteria-mediated. Furthermore it was found that exposure of human HeLa epithelial cells to both LFchimera and the bacterial strains evoked a pro-inflammatory cytokine release from the cells in vitro.
Insights
The peptide LFchimera shows potential against Yersinia infections by inhibiting bacterial invasion of host cells. This study explored LFchimera
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Yersinia pestis causes plague, necessitating alternative therapies due to limited antibiotics and no vaccines.
- Antimicrobial peptides offer a promising avenue for novel therapeutic strategies.
- LFchimera, derived from bovine lactoferrin, exhibits broad-spectrum antimicrobial activity.
Purpose of the Study:
- To evaluate the therapeutic potential of LFchimera against Yersinia enterocolitica and Yersinia pseudotuberculosis in vitro.
- To investigate LFchimera's effect on Yersinia spp. adherence and invasion of host cells.
- To determine the mechanism underlying LFchimera's impact on host-pathogen interactions.
Main Methods:
- In vitro assays using Yersinia enterocolitica and Yersinia pseudotuberculosis as simulants for Yersinia pestis.
- Assessment of LFchimera's antimicrobial activity and its effects on bacterial invasion of human HeLa epithelial cells.
- Analysis of host-cell mediated responses, including pro-inflammatory cytokine release upon exposure to LFchimera and Yersinia spp.
Main Results:
- LFchimera demonstrated susceptibility against Yersinia enterocolitica and Yersinia pseudotuberculosis in vitro.
- LFchimera effectively inhibited the invasion of host cells by Yersinia spp. in a host-cell mediated manner.
- Co-exposure to LFchimera and Yersinia strains induced pro-inflammatory cytokine release from human epithelial cells.
Conclusions:
- LFchimera exhibits therapeutic potential against Yersinia infections by interfering with host cell invasion.
- The study highlights a host-cell mediated mechanism for LFchimera's anti-invasion activity.
- LFchimera's ability to modulate host inflammatory responses warrants further investigation for plague treatment strategies.
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