title: Campylobacter jejuni carbon starvation protein A (CstA) is involved in peptide utilization, motility and agglutination, and has a role in stimulation of dendritic cells.
abstract: Campylobacter jejuni is the most frequent cause of severe gastroenteritis in the developed world. The major symptom of campylobacteriosis is inflammatory diarrhoea. The molecular mechanisms of this infection are poorly understood compared to those of less frequent disease-causing pathogens. In a previous study, we identified C. jejuni proteins that antibodies in human campylobacteriosis patients reacted with. One of the immunogenic proteins identified (Cj0917) displays homology to carbon starvation protein A (CstA) from Escherichia coli, where this protein is involved in the starvation response and peptide uptake. In contrast to many bacteria, C. jejuni relies on amino acids and organic acids for energy, but in vivo it is highly likely that peptides are also utilized, although their mechanisms of uptake are unknown. In this study, Biolog phenotype microarrays have been used to show that a ΔcstA mutant has a reduced ability to utilize a number of di- and tri-peptides as nitrogen sources. This phenotype was restored through genetic complementation, suggesting CstA is a peptide uptake system in C. jejuni. Furthermore, the ΔcstA mutant also displayed reduced motility and reduced agglutination compared to WT bacteria; these phenotypes were also restored through complementation. Murine dendritic cells exposed to UV-killed bacteria showed a reduced IL-12 production, but the same IL-10 response when encountering C. jejuni ΔcstA compared to the WT strain. The greater Th1 stimulation elicited by the WT as compared to ΔcstA mutant cells indicates an altered antigenic presentation on the surface, and thus an altered recognition of the mutant. Thus, we conclude that C. jejuni CstA is important not only for peptide utilization, but also it may influence host-pathogen interactions.
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, 2300 Copenhagen S, Denmark.|Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: Rasmussen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.
authors.forename: C S
authors.initials: CS
authors.lastname: Vegge
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Frøkiær
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Howlett
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, 2300 Copenhagen S, Denmark.
authors.forename: K A
authors.initials: KA
authors.lastname: Krogfelt
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kelly
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Ingmer
mesh_terms: D000371:Agglutination; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002169:Campylobacter Infections / Q000276:immunology / Q000382:microbiology*; D016123:Campylobacter jejuni / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002244:Carbon / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D004151:Dipeptides / Q000378:metabolism*; D005260:Female; D005816:Genetic Complementation Test; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000032:analysis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D016415:Sequence Alignment; D017384:Sequence Deletion
chemical_list: D001426:Bacterial Proteins; D004151:Dipeptides; D018664:Interleukin-12; D002244:Carbon; D009584:Nitrogen